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NCT05079789
11.7
Continuous Information to Independent Ethic Committee
According to the German Drug Law (AMG) and the GCP Ordinance, the EC and the competent authority will be informed of all suspected serious unexpected adverse reactions (SUSARs). Both institutions will be informed in case the risk/ benefit assessment did change or any others new and significant hazards for subjects' saf...
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NCT05079789
11.8
Approval of Protocol and Subsequent Amendments
Before the start of the trial, the trial protocol, informed consent document, and any other appropriate documents will be submitted to the independent Ethics Committee (EC) as well as to the competent authority (BfArM or PEI). A written favourable vote of the EC and an (implicit) approval by the competent higher federa...
[ "12.Publications" ]
NCT05079789
12.1
Reports
Within one year of the completion of the trial, the competent authority and the ethics committee will be supplied with a summary of the final report on the clinical trial containing the principle results. All reports to the sponsor will be written in English language. All clinical, analytical and statistical results w...
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NCT05079789
12.2
Publication
The final results of this study will be presented at scientific meetings and published in a peer reviewed leading medical journal of general medicine or a leading nephrological journal. All publications in result of this study are the responsibility of the principal coordinating investigator and the authorship will ref...
[ "13.Financing", "14.Literature", "15.Appendices" ]
NCT05118386
1
Protocol Summary
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NCT05118386
1.1
Synopsis
Protocol Title: A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of RSM01, a Monoclonal Antibody Targeting Respiratory Syncytial Virus, in Healthy Adults Short Title: Safety, Tolerability, and Pharmacokinetics of RSV Mono...
[ "Overall Design", "Dose Escalation Phase:", "Dose Expansion Phase:", "Pausing Rules" ]
NCT05118386
1.2
Schema
Figure 1: Outline of Study Dosing Procedures ![](_page_15_Figure_3.jpeg)
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NCT05118386
1.3
Schedule of Activities (SoA)
The SoA for the Dose Escalation Phase (Coho1t s 1-4) is presented in Table 2 and the SoA for the Expansion Phase (Coho1t 5) is presented in Table 3. Table 2: Schedule of Activities for the Dose Escalation Phase (Cohorts 1-4) Table 2 continued: Schedule of Activities for the Dose Escalation Phase (Cohorts 1-4) | ...
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NCT05118386
2
Introduction
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NCT05118386
2.1
RSV and Burden of Disease
RSV is the most common pathogen identified in young children with acute LRTI. Most children acquire an RSV infection by the time they are 2 years old, causing a mild, cold-like illness within 4 to 6 days after infection. However, in some children it leads to a more severe illness such as bronchiolitis and pneumonia and...
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NCT05118386
2.2
RSV Prevention- Monoclonal Antibodies
There is an unmet medical need for an effective, durable, cost effective RSV prevention strategy for all infants and children. The World Health Organization (WHO) Product Development for Vaccines Advisory Committee (PDVAC) indicates that RSV immunoprophylaxis with a monoclonal antibody (mAb) is a priority intervention....
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NCT05118386
2.3
RSM01 mAb Candidate
RSM01(also designated as ADI-15618-IVNS YTE) is a fully human IgG1 neutralizing monoclonal antibody that targets site Ø (zero) of the prefusion conformation of the RSV F glycoprotein (pre-F), which has high neutralizing potency. RSM01 has a molecular weight of approximately 150 kilodaltons. RSM01 has the same half-lif...
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NCT05118386
2.3.1
Non-Clinical Development of RSM01
The non-clinical development of RSM01 focused on non-clinical safety studies in rats and monkeys, in vitro potency against RSV A and B assessments and efficacy studies in a cotton rat RSV challenge model. These studies are considered sufficient to support entry into Phase 1 FiH study in adults, followed by age de-escal...
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NCT05118386
2.4
Study Rationale
The burden of RSV infection, especially among infants and young children underscores the need for safe and effective prevention against RSV disease that is affordable in LMICs. The goal of the clinical development program for RSM01 is to develop a safe, effective, affordable mAb to prevent severe RSV disease in infants...
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NCT05118386
2.5
Justification for Dose
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NCT05118386
2.5.1
Doses for Escalation Phase Cohorts
The selection of the dosing strategy for dose escalation is based on non-clinical safety data and in vivo pharmacological evaluation in the cotton rat RSV prophylactic model. This approach is supported by assessments of the PK profile of other RSV mAbs with YTE mutations. The wide dose range, from 300mg to 3000mg, in ...
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NCT05118386
2.5.2
Dose for Expansion Phase Cohort
Final selection of the dose to be administered to Cohort 5 will be made by the sponsor and informed by available RSM01 PK data, as well as relevant safety data, from the Dose Escalation Phase. Available interim PK data from the Dose Escalation Phase cohorts, combined with published data from previous studies of monocl...
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NCT05118386
2.6
Benefit/Risk Assessment
The non-clinical safety of RSM01 has been evaluated in GLP-compliant studies in monkeys of up to 4 weeks in duration. RSM01 was well-tolerated at all doses tested; there were no testarticle related target organ toxicities, no effects on vital systems, and no adverse local reactions. Juvenile monkeys are commonly used i...
[ "RSV Mutations", "General Risks with MAb Infusion" ]
NCT05118386
3
Objectives and Endpoints
Table 4: Objectives and Endpoints | Objectives | Endpoints (Endpoints apply to all cohorts unless noted) ...
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NCT05118386
4
Study Design
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NCT05118386
4.1
Design Overview
Disclosure statement: This is a FiH trial of RSM01, administered to adults. It is a randomized, double-blind, placebo-controlled study of RSM01. Study Population and Number of Participants: Adult participants between 18 and 49 years of age (inclusive) of both sexes who are capable of and willing to provide informed ...
[ "Overall Design", "Dose Escalation Phase:", "Dose Escalation Phase, continued:", "Dose Expansion Phase:" ]
NCT05118386
4.2
End of Study Definition
A participant is considered to have completed the study if he/she completes the final visit at Day 151. The end of the study is defined as the date of the last visit of the last participant in the study or conduct of the last scheduled procedure shown in the SoA for the last participant in the trial.
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NCT05118386
5
Study Population
A total of 56 eligible, healthy adult participants between 18 and 49 years of age (inclusive) of both sexes who are capable of and willing to provide informed consent will be eligible for the study. See Section 5.1 and 5.2 for inclusion and exclusion criteria, respectively. Candidates will be screened for eligibility t...
[ "Recruitment" ]
NCT05118386
5.1
Inclusion Criteria
1. Participant must be 18 to 49 years of age (inclusive) at the time of signing the informed consent 2. Participants who are healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests 3. Body mass index (BMI) 18 to 29.9 kg/m2 (inclusive) 4. Both males and fema...
[ "Age", "Type of Participant and Disease Characteristics", "Weight", "Sex", "Informed Consent", "Additional Requirements:" ]
NCT05118386
5.2
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply: - 1. Acute illness and/or body temperature ≥37.5°C or ≥99.5°F on Study Day 1 (refer to Section 5.4 for additional details). NOTE: This is a temporary exclusion for which the participant may be re-evaluated. - 2. Evidence and/or history of...
[ "Medical Conditions", "Prior/Concomitant Therapy", "Prior/Concurrent Clinical Study Experience", "Diagnostic Assessments", "Other Exclusions" ]
NCT05118386
5.3
Lifestyle Considerations
No restrictions are required.
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NCT05118386
5.4
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but are not subsequently entered into the study and do not receive study intervention. A minimal set of screen failure information is required to ensure transparent reporting of criteria for participants who are screen failures...
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NCT05118386
6
Study Intervention
Study intervention is defined as any investigational intervention(s), marketed product(s), Placebo, or medical device(s) intended to be administered to a study participant according to the study protocol. Two interventions will be used in this study: participants will receive either RSM01 or Placebo based on randomiza...
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NCT05118386
6.1
RSM01 Drug Product
The RSM01 Drug Product (RSM01) used in this study is manufactured by Just-Evotec Biologics, Inc. RSM01 is supplied as a liquid in a single use, sterile filled glass vial at a product concentration of 100mg/mL, and 100mg/vial configuration. The volume injected or infused will vary depending on the cohort. Each vial con...
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NCT05118386
6.2
Placebo Drug Product
The RSM01 Placebo Drug Product (Placebo) control consists of all the excipients without the mAb, in the same type of vial/cap/seal fill as the RSM01 presentation. The volume injected or infused will depend on the randomized group and will be the same as the volume of the RSM01 administered to participants within each r...
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NCT05118386
6.3
Study Intervention Preparation and Administration
Refer to Section 4.1 for dose administration within each cohort and Section 6.4 for handling, storage, and accountability. Unit-dose syringes will be provided for IM administration, and infusion bags for IV administration, all of which will be identified with the participant identification number, date and time of dos...
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NCT05118386
6.3.1
IM Injection
Before administering the injection, the study intervention administrator must inspect the syringe and vial volume, checking that the syringe is identified with the correct participant identification number and checking the date and time the dose was prepared. For IM dosing in the Dose Escalation Phase, participants in ...
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NCT05118386
6.3.2
IV Infusion
The formulation for RSM01 is 100mg/mL, and the appropriate volume, based on group randomization, will be added to normal saline to achieve the desired volume for each of the IVdosed cohorts. The total IV infusion volume will be 53mL for Cohort 1, 60 mL for Cohort 3, and 130mL for cohort 4. The IV infusion time will be ...
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NCT05118386
6.4
Handling/Storage/Accountability
Further guidance and information for the preparation, handling, storage, and accountability are provided in the Pharmacy Manual. The study intervention (RSM01 and Placebo) must be stored at 2°C to 8°C in a secure location with no access for unauthorized personnel. The study pharmacist (or designee) must confirm appro...
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NCT05118386
6.5
Measures to Minimize Bias: Randomization and Blinding
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NCT05118386
6.5.1
Randomization
The first participant in each Dose Escalation Phase cohort will not be randomized and will receive RSM01 dose level appropriate to the assigned cohort (refer to Section 8.1.1). The remaining 6 participants in each Dose Escalation Phase cohort (Cohorts 1, 2, 3 and 4) will be randomized 5:1 to receive either RSM01 or Pl...
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NCT05118386
6.5.2
Masking
The study is double-blind: participants and all study personnel will be blinded to the randomization, with one exception: the first sentinel participant in each Dose Escalation Phase cohort will be single-blinded (participant-blinded) and receive the respective dose of RSM01. Authorized study site personnel will admini...
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NCT05118386
6.5.3
Blind Break
The IXRS will be programmed with blind-breaking instructions. In addition, instructions on emergency unblinding in case of system outage will be provided. In case of an emergency, the investigator has the sole responsibility for determining if unblinding of a participant's treatment assignment is warranted. Participant...
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NCT05118386
6.6
Study Intervention Compliance
Participant compliance with study intervention will be recorded on his/her CRF.
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NCT05118386
6.7
Concomitant Therapy
Any prescription medication, anti-inflammatory drug, antipyretic drug, or vaccine that the participant receives from enrollment through study Day 151 must be recorded along with: - Reason for use - Dates of administration including start and end dates - Dosage information including dose and frequency. The Medical Mon...
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NCT05118386
6.8
Dose Modification
No unplanned dose modifications are allowed. This is a dose escalation and dose expansion study. Refer to Section 3 for details regarding dose escalation and dose expansion.
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NCT05118386
7
Discontinuation of Study Intervention and Participant Discontinuation/Withdrawal
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NCT05118386
7.1
Discontinuation of Study Intervention
A participant withdrawn from the study intervention (i.e., any participant who does not receive the study intervention) will be withdrawn from the study.
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NCT05118386
7.1.1
Pausing Rules
Pausing rules (reasons for pausing the study) are in effect during the active enrollment and dosing period. Any one of the following will prompt a study pause: - death in any participant in whom the event causing death is judged to be related to the study drug by the investigator. - any occurrence in any participant o...
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NCT05118386
7.2
Participant Discontinuation or Withdrawal from the Study
A participant may request withdrawal from the study at any time. A participant may also be withdrawn from the study at any time for the following reasons: - a. at the request of the primary care provider if being in the study is no longer in the best interest of the participant - b. participant is judged by the invest...
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NCT05118386
7.3
Lost to Follow-up
A participant will be considered lost to follow-up if he or she repeatedly fails to return for scheduled visits (3 failed visits) and is unable to be contacted by the study site (3 failed attempts per failed visit). The following actions must be taken if a participant fails to return to the clinic for a required study...
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NCT05118386
7.4
COVID-19 Contingency Plans
In the event that SARS-CoV-2 coronavirus disease (COVID-19) affects the conduct of this trial, the sponsor will evaluate if in-person visits are necessary to fully ensure the safety of trial participants and whether alternative methods for safety assessments (e.g., phone contact, virtual visit, alternative location for...
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NCT05118386
8
Study Assessments and Procedures
Study procedures and their timing are summarized in the SoA. Adherence to the study protocol, including those specified in the SoA, is essential and required for study conduct. Prior to any study procedure, all eligible participants will be assigned a unique participant identifier. This participant identifier will be ...
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NCT05118386
8.1
Safety Assessments
The screening visit will take place between 30 days and 2 days before the planned Day 1 visit. All participants will also be required to attend the Day -1 (Pre-V1) visit within 24 hours before planned dosing to begin confinement. A negative serum pregnancy test (based on the serum sample collected on Day -1) must be ...
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NCT05118386
8.1.1
Confinement Period and Sentinel Participants
Details regarding confinement period are provided in the study manual. Participants in the Dose Escalation Phase will be confined at the study site from Day -1 to after completion of Day 3 assessment (a total of 3 nights). On Day -1, participants will undergo safety laboratory assessments and other screening procedur...
[ "Dose Escalation Phase", "Dose Expansion Phase" ]
NCT05118386
8.1.2
Full Physical Examination and Medical History
A full physical examination and medical history will be conducted at screening to assess enrollment eligibility. Only participants that are considered as healthy by the investigator will be enrolled. All conditions that exist prior to administration of study intervention will be recorded in the medical history. Day-to...
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NCT05118386
8.1.2.1
Vital Signs
Vital signs will be taken at screening and on Day 1, prior to RSM01/Placebo administration. Vital sign measurements will be recorded for pulse rate, systolic and diastolic blood pressure, respiratory rate, body temperature and percent oxygen saturation by fingertip pulse oximetry. Vital signs are to be taken after the...
[ "Vital signs for the Dose Escalation Phase:", "Vital signs for the Dose Expansion Phase:" ]
NCT05118386
8.1.3
Focused Physical Examination and Medications/Vaccinations
Focused physical examinations, will be performed on Day 1 and all subsequent visits, as indicated in the SoA (Table 2 and Table 3). A focused physical examination will be performed if indicated by participant's medical complaint and will include assessments of body systems involved in the complaint. Focused physical e...
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NCT05118386
8.1.4
Pregnancy Status Assessment
A blood sample will be collected from female participants at screening and at Day -1 for serum beta human chorionic gonadotropin (βHCG) testing. Serum βHCG testing of female participants should be performed during the study if a pregnancy is suspected. Serum βHCG testing of female participants of childbearing potenti...
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NCT05118386
8.1.5
HIV Antibody Assessment
To be eligible for the study, participants must not have reactive anti-HIV antibody at screening. A blood sample will be collected to make this assessment.
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NCT05118386
8.1.6
Electrocardiogram, Hepatitis Screening and Urine Drug Screening
A 12-lead ECG will be performed at screening using a machine that automatically calculates heart rate and determines intervals for PR, QRS, QT and QTc. Triplicate (unmarked) 12-lead ECGs will be obtained. For the Dose Escalation Phase, the ECGs will be taken at screening, and 24 hours post-dose, on Day 2. For the Dose ...
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NCT05118386
8.1.7
Clinical Safety Laboratory Assessments
Clinical safety laboratory assessments will be performed at screening, on Day -1 (Pre-V1), and throughout the study at timepoints specified in the SoA (Section 1.3). Blood samples for laboratory assessments will be collected at screening, and at study visits indicated in the SoA. Laboratory values from the most recen...
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NCT05118386
8.1.8
Pre- and Post-Study Intervention Safety Monitoring
Participants will remain under observation at the study site for 3 days in the Dose Escalation Phase cohorts (24 hours before dosing and 48 hours after dosing). Participants in the Dose Expansion Phase cohort will present to the study site before the planned Day 1 visit. After treatment on Day1, the participant will be...
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NCT05118386
8.1.9
Diary Card, Memory Aid and Daily Monitoring
Before leaving the clinic after dosing and completion of the post-dosing on-site confinement, participants will be given a diary card and receive guidance on how to fill in the card. All participants will receive a digital thermometer to record temperature. Participants who receive an IM dose will also receive a rule...
[ "Diary card", "Memory aid" ]
NCT05118386
8.1.10
Participant Follow-Up
Participants will be instructed to contact a study team member to report new or worsening AEs, as well as new diagnoses, and to come to the study clinic if medical attention is needed. For emergencies and other unscheduled visits to a medical facility other than the study clinic, medical records will, to the extent po...
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NCT05118386
8.2
Adverse Events and Serious Adverse Events
Local injection site solicited AEs will include pain, redness and swelling, and will be assessed after dosing at Visit 1 for 7 days (IM recipients only). If more than 1 injection is given, reactions will be assessed separately at each injection site. Systemic solicited AEs will be assessed in all participants after do...
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NCT05118386
8.2.1
Time Period and Frequency for Collecting AE and SAE Information
| Type of Event | Collection Time Period | |-------------------------------------------|------------------------------------------| | All solicited AEs | Day 1 through Day 7 (inclusive) | | Unsolicited AEs, and SAEs including AESIs | Screeni...
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NCT05118386
8.2.2
Method of Detecting AEs and SAEs
The methods of recording and follow-up of AEs, SAEs and AESIs are provided in detail in Appendix 2, Section 10.2.5, which includes assessments of intensity, relationship to the study intervention, and outcome of AEs, SAE and AESIs. Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and...
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NCT05118386
8.2.3
Follow-up of AEs
After the initial SAE/AESI report, the investigator is required to proactively follow each participant at subsequent visits/contacts. All SAEs/AESIs will be followed until resolution, stabilization, or the participant is withdrawn/withdraws, or is lost to follow-up or (as defined in Section 7.2 and Section 7.3, respect...
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NCT05118386
8.2.3.1
AE Intensity
The intensity of AEs will be classified by the investigator based on the toxicity grading tables (Section 10.4 Appendix 4). In the case of an AE or abnormal clinical laboratory result not included in Appendix 4, intensity will be assigned using the Grades described in the U.S. Department of Health and Human Services, C...
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NCT05118386
8.2.3.2
AE Causality/Relationship to Study Intervention
All AEs will be evaluated by the investigator or medically qualified designee (i.e., investigator, sub-investigator) to assess the relationship between study intervention and the AE (with the exception of local injection site reactions, which are assumed to be related to the injection). Careful medical judgment should ...
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NCT05118386
8.2.4
Regulatory Reporting Requirements for SAEs
Refer to Appendix 2, Section 10.2.6 for details regarding SAE reporting. The sponsor or delegate has a legal responsibility to notify both the local regulatory authority and potentially other regulatory agencies about the safety of the study intervention under clinical investigation. Therefore, prompt notification by ...
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NCT05118386
8.2.5
Death Events
Any untoward medical occurrence (AE) resulting in death is reported as an SAE. The cause of death will be appropriately documented in the SAE report form and supporting evidence will be provided.
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NCT05118386
8.2.6
Safety Review Team
A SRT will be established as the team responsible for recommending dose escalation or dose expansion to the sponsor's Chief Medical Officer. The SRT will operate according to the Safety Review Team Plan. Meetings of the SRT to provide a recommendation on dose escalation or dose expansion will occur during the Dose Esc...
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NCT05118386
8.2.7
Independent Data Monitoring Committee
The IDMC will operate according to a charter approved by the sponsor and all IDMC members. The IDMC structure, participants and other details will be provided in the charter. The charter will be approved prior to enrollment of the first study participant. The role of the IDMC will be to (a) review unblinded safety dat...
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NCT05118386
8.3
Treatment of Overdose
Overdose of any study intervention (including Placebo) is unlikely to occur since the injections and infusions are administered as a single dose by a trained study staff member. If an overdose were to occur, the overdose, including misuse or abuse of the product and medication errors, should be reported in in the clini...
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NCT05118386
8.4
Blood Sampling
Refer to the SoA for blood sample collection at screening for eligibility and safety laboratory assessments. Blood samples will be collected for pregnancy test, HIV, hepatitis B, hepatitis C and safety laboratory assessments as described in Section 8.1.7. Whole blood samples will be collected for measurement of PK, AD...
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NCT05118386
8.5
Pharmacokinetics
Dose Escalation Phase: At Visit 1, PK blood draw will occur at pre-dosing, 1 hour (+/- 30 minutes) before administration of IM injection or beginning of infusion, for all participants in Cohorts 1-4. For participants who receive IV study intervention, the timing of post-dose blood samples begins at the end of the IV in...
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NCT05118386
8.6
Pharmacodynamics
For this study, pharmacodynamics is being assessed as an exploratory endpoint. A surrogate pharmacodynamic marker will be used, measuring the ex vivo capability of RSM01 to neutralize RSV. Whole blood samples in serum separator tubes and VAMS devices will be collected for detection of RSV neutralizing antibodies in se...
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NCT05118386
8.7
Genetics
No genetic testing will be performed for this trial.
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NCT05118386
8.8
Biomarkers
There are no prospective biomarker analyses planned. As dictated by clinical data and emerging science, the non-genetic biomarkers may be added during trial execution. These will be clearly documented in the clinical study report (CSR) and/or the trial master file (TMF). Clinical safety laboratory assessments such as...
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NCT05118386
8.9
Immunogenicity
Whole blood samples in serum separator tubes and VAMS samples will be collected for detection of ADA against RSM01 in serum and capillary blood respectively, as specified in the SoA. Samples on Day 1 will be collected prior to RSM01 administration. The detection of ADA to RSM01 will be performed using a validated immu...
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NCT05118386
9
Statistical Considerations
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NCT05118386
9.1
Sample Size Determination
This trial is an exploratory trial to characterize safety, tolerability, and pharmacokinetics of single doses of RSM01 mAb. The trial is designed to be descriptive and is not based on formal testing of a null hypothesis. Therefore, this study is not powered to detect any differences in potential safety data between tre...
[ "Safety" ]
NCT05118386
9.2
Populations for Analyses
Analysis populations are shown in Table 6. Table 6: Populations for Analyses | Population | Description ...
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NCT05118386
9.3
Statistical Analyses
A detailed statistical analysis plan (SAP) centered on primary and secondary endpoints will be developed and finalized prior to unblinding the study and will further describe the participant populations to be included in each analysis, details of the statistical methods, including procedures for accounting for missing,...
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NCT05118386
9.3.1
Safety Primary Endpoints
The primary analysis will occur when all participants reach Day 151. All safety summaries will be presented for all participants in the safety population. All solicited local AEs will be considered study intervention-related events and will be summarized for each injection site. All solicited AEs collected from Day 1...
[ "Solicited Local and Systemic AEs", "Unsolicited Treatment Emergent AEs, SAEs and AESI" ]
NCT05118386
9.3.2
Safety Secondary Laboratory Assessments
Clinical safety laboratory evaluations are listed in Section 8.1.7. All laboratory values collected at visits will be included in the summaries and listings. Descriptive summaries (n, mean, standard deviation, median, minimum, and maximum) of observed value and change from baseline (last result available on or before D...
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NCT05118386
9.3.3
Other Safety Measures
Vital signs, 12-Lead ECG, medical history, and summary statistics will be tabulated by treatment group. Any other relevant information will be presented in participant data listings. Further details will be provided in the SAP.
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NCT05118386
9.3.4
Pharmacokinetics
All available PK data will be summarized at the time of dose selection for the Dose Expansion Phase, and for the interim and primary analyses when all participants reach Day 91 and Day 151, respectively. RSM01 capillary blood concentrations and the following PK parameters, AUC0-∞, , AUC0-t, Cmin, Cmax ,or C0, CD91, CD...
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NCT05118386
9.4
Serum and Capillary Blood Immunogenicity
All available ADA results will be summarized for each treatment cohort at the time of the primary analyses, when all participants reach Day 151. Further details will be specified in the SAP for capillary blood analyses and in the exploratory SSAP for serum.
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NCT05118386
9.5
Serum and Capillary Blood RSV Neutralizing Antibody
All available serum RSV neutralizing antibodies will be summarized for each treatment cohort at the time of the primary analysis, when all participants reach Day 151 Analyses will be specified in the exploratory SSAP.
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NCT05118386
9.6
Demographic and Compliance Analyses
Demographic parameters (age, sex, and race/ethnicity) and other baseline characteristics will be summarized descriptively by treatment group for all participants in the safety population. Listings of randomized participants with protocol deviations (to be defined in the SAP) will be presented by treatment group.
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NCT05118386
9.7
Interim Analyses
An interim analysis is planned for this study when all participants in each of the Dose Escalation Phase cohorts have completed Day 91. An Interim Report will be prepared when the results from Day 91 become available. Additional interim analyses may occur prior to the primary analysis to aid in the development of indiv...
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NCT05118386
9.8
National Regulatory Authority
The national regulatory authority will receive all expedited safety reports from the clinical trial and have the authority to terminate, suspend or require changes to a clinical trial.
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NCT05118386
10
Supporting Documentation and Operational Considerations
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NCT05118386
10.1
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
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NCT05118386
10.1.1
Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following: - a. Consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines - b. Applicable Int...
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NCT05118386
10.1.2
Study Oversight
The study sponsor, the institution through which the research is performed and all members of the investigator's clinical team and the national regulatory authority share responsibility for ensuring the safety of participants in this trial. The investigator will be responsible for the following: - a. Providing writte...
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NCT05118386
10.1.3
Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial information as requested to allow the sponsor to submit complete and accurate financial certification or disclosure statements to the appropriate regulatory authorities. Investigators are responsible for providing informati...
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NCT05118386
10.1.4
Informed Consent Process
The investigator or designee will explain the study to the participant and answer all questions regarding the study. The investigator or designee will conduct the consent discussions on an individual basis with each participant. Adequate time will be allowed for all questions to be addressed. Potential participants wil...
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NCT05118386
10.1.4.1
Informed Consent Forms
Participants will be required to sign a statement of informed consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study center. Participants will be told that they are free to...
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NCT05118386
10.1.5
Data Protection
Participants will be assigned a unique identifier by the sponsor. Any participant record or dataset that is transferred to the sponsor will contain the identifier only; participant names or any information which would make the participant identifiable will not be transferred to the sponsor. The participant must be inf...
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NCT05118386
10.1.6
Dissemination of Clinical Study Data
Study information from this protocol will be posted on publicly available clinical trials registers (for example, clinicaltrials.gov) before enrollment of participants begins. Summaries of the results of the study will also be posted on the same website. The final CSR will include all available data through the final ...
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NCT05118386
10.1.7
Data Quality Assurance
All participant data relating to the study will be recorded by an electronic CRF using an EDC system or transmitted to the sponsor or designee electronically (e.g., laboratory data). The investigator is responsible for verifying that data entries are accurate and correct by electronically signing the CRF. The investig...
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