protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
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NCT04339062 | 5.2 | Pre-Treatment Criteria | 5.2 Pre-Treatment Criteria | [] |
NCT04339062 | 5.2.1 | Cycle 1, Day 1 | 5.2.1 Cycle 1, Day 1 Laboratory evaluations need to be repeated (except mTOR monitoring levels) and reviewed to re-meet eligibility criteria on Cycle 1, Day 1. In Cohort 2, patients must be on mTOR inhibition and have taken their 40 mg prednisone oral dose prior to cemiplimab on Cycle 1, Day 1. | [] |
NCT04339062 | 5.2.2 | Subsequent Cycles | 5.2.2 Subsequent Cycles Reasonable effort should be made to conduct study visits on the day scheduled ( 3 days). Laboratory evaluations should be reviewed prior to the start of each cycle. Any changes from screening clinical evaluation findings that meet the definition of an adverse event (AE) will be recorded on the A... | [] |
NCT04339062 | 5.3 | Agent Administration | 5.3 Agent Administration | [] |
NCT04339062 | 5.3.1 | Cemiplimab | 5.3.1 Cemiplimab No pre-medications are recommended prior to the administration of cemiplimab. Day -1 prednisone is part of dynamic immunosuppression, not pre-medication. Cemiplimab (350 mg flat dose IV every 21 days) will be administered in an outpatient setting as an approximately 30-minute infusion (+/- 20 minutes).... | [] |
NCT04339062 | 5.3.2 | Dynamic Immunosuppression (Cohort 2) | 5.3.2 Dynamic Immunosuppression (Cohort 2) Participants in Cohort 2 will receive everolimus or sirolimus and prednisone on an outpatient basis. Everolimus or sirolimus pills can be taken with or without food as prescribed based on desired dosing (although ingestion of a high-fat meal should be avoided with sirolimus). ... | [] |
NCT04339062 | 5.4 | General Concomitant Medication and Supportive Care Guidelines | 5.4 General Concomitant Medication and Supportive Care Guidelines | [] |
NCT04339062 | 5.4.1 | Concomitant Medical Guidelines | 5.4.1 Concomitant Medical Guidelines Pertinent concomitant medications will be recorded on the case report form (CRF). If changes occur during the trial period, documentation of drug dosage, frequency, route, and date may also be included on the CRF. Topical, intradermal, and intraarticular corticosteroids are permitte... | [] |
NCT04339062 | 5.4.2 | CYP3A4 Interactions among mTOR inhibitors | 5.4.2 CYP3A4 Interactions among mTOR inhibitors mTOR inhibitors are a known substrate of CYP3A4 and P-glycoprotein/ABCB1 and therefore medications which can cause drug-drug interactions are listed in the Table below. Strong inducers of CYP3A4 are identified below with monitoring during concomitant therapy recommended. ... | [] |
NCT04339062 | 5.5 | Criteria for Taking a Participant Off Protocol Therapy | 5.5 Criteria for Taking a Participant Off Protocol Therapy Duration of therapy will depend on individual response, evidence of disease progression and tolerance. In the absence of treatment delays due to adverse event(s), treatment may continue until any of the following criteria applies: - Disease progression - Interc... | [] |
NCT04339062 | 5.6 | Duration of Follow-Up | 5.6 Duration of Follow-Up Participants will be followed for best overall response and development and documentation of first disease progression and for survival throughout the course of the trial for 1 years from the time of end of treatment visit Participants who are removed from protocol therapy for an unacceptable ... | [] |
NCT04339062 | 5.7 | Criteria for Taking a Participant Off Study | 5.7 Criteria for Taking a Participant Off Study Protocol Version Date: May 3, 2023 Participants will be removed from study when any of the following criteria apply: - Lost to follow-up - Withdrawal of consent for data submission - Death The reason for taking a participant off study, and the date the participant was rem... | [] |
NCT04339062 | 6 | DOSING DELAYS/DOSE MODIFICATIONS | 6. DOSING DELAYS/DOSE MODIFICATIONS Dose delays and modifications will be made as indicated below. The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for dose delays and dose modifications. A copy of the CTCAE version 5.0 can ... | [] |
NCT04339062 | 6.1 | Cemiplimab | 6.1 Cemiplimab There will be no dose reductions for cemiplimab permitted. Doses of cemiplimab may be interrupted, delayed, or discontinued depending on how well the participant tolerates the treatment. Cemiplimab dosing visits are not skipped, only delayed. If cemiplimab doses are delayed or skipped, study testing resu... | [] |
NCT04339062 | 6.1.1 | Cemiplimab Dose Delays or Holds | 6.1.1 Cemiplimab Dose Delays or Holds Administration of cemiplimab should be delayed and the dose held for the following adverse events: - Grade II, III, or IV acute GVHD according to the modified Glucksberg scale (see Section 7.7) in Cohort 1 - Moderate to severe chronic GVHD by the revised NIH consensus scoring syste... | [] |
NCT04339062 | 6.1.2 | Re-treatment Criteria for Cemiplimab | 6.1.2 Re-treatment Criteria for Cemiplimab Participants who require delay of cemiplimab should be re-evaluated weekly or more frequently if clinically indicated and resume dosing when re-treatment criteria (as described below) are met. Participants with a delay in dosing beyond 12 weeks should be considered for discont... | [] |
NCT04339062 | 6.1.3 | Cemiplimab Discontinuation | 6.1.3 Cemiplimab Discontinuation Administration of cemiplimab should be discontinued for the following AEs: - Unresolved Grade II, III, or IV acute GVHD according to the modified Glucksberg scale despite 14 days (or 2 weeks) of systemic corticosteroids (see Section 7.6.1) in Cohort 1 - Any degree of biopsy proven acute... | [] |
NCT04339062 | 6.2 | Dynamic Immunosuppression | 6.2 Dynamic Immunosuppression Dose delays of prednisone and mTOR inhibition are discouraged as to promote immune tolerance of the bone marrow and kidney organ graft while the patient is receiving immune checkpoint blockade with cemiplimab. Dose modifications for prednisone may be required outside of the planned treatme... | [] |
NCT04339062 | 7 | ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS | 7. ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS Adverse event (AE) monitoring and reporting is a routine part of every clinical trial. The following list of reported and/or potential AEs (Section 7.1) and the characteristics of an observed AE (Section 7.2) will determine whether the event requires expedited reportin... | [] |
NCT04339062 | 7.1.1 | Adverse Events List | 7.1.1 Adverse Events List | [] |
NCT04339062 | 7.1.1.1 | Adverse Event List(s) for cemiplimab | 7.1.1.1 Adverse Event List(s) for cemiplimab The most common adverse reactions (> 10%) related to cemiplimab alone are: diarrhea, fatigue, nausea, constipation, rash, cough, decreased appetite, pruritis, and headache [10]. It is important to distinguish common immune-related AEs from cemiplimab with manifestations of a... | [] |
NCT04339062 | 7.1.1.2 | Adverse Event List(s) for mTOR inhibitors, Everolimus and Sirolimus | 7.1.1.2 Adverse Event List(s) for mTOR inhibitors, Everolimus and Sirolimus | [] |
NCT04339062 | 7.1.1.2.1 | Everolimus | 7.1.1.2.1. Everolimus Stomatitis, infections, rash, fatigue, diarrhea, edema, abdominal pain, nausea, fever asthenia, cough, headache, and decreased appetite. Please see package insert for a comprehensive list of adverse events. | [] |
NCT04339062 | 7.1.1.2.2 | Sirolimus | 7.1.1.2.2. Sirolimus Peripheral edema, hypertriglyceridemia, hypertension, hypercholesterolemia, creatinine increased, abdominal pain, diarrhea, headache, fever, urinary tract infection, anemia, nausea, arthralgia, pain, and thrombocytopenia. Please see package insert for a comprehensive list of adverse events. | [] |
NCT04339062 | 7.1.1.3 | Adverse Event List for Prednisone | 7.1.1.3 Adverse Event List for Prednisone Fluid retention, alteration in glucose intolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain. Please see package insert for a comprehensive list of adverse events. | [] |
NCT04339062 | 7.2 | Adverse Event Characteristics | 7.2 Adverse Event Characteristics An adverse event (AE) is any undesirable sign, symptom or medical condition, or experience that develops or worsens in severity after starting the first dose of study treatment (cemiplimab) specified in the protocol, even if the event is not considered to be related to the study. Abnor... | [
"• For expedited reporting purposes only:",
"Attribution of the AE:"
] |
NCT04339062 | 7.3 | Adverse Event Reporting | 7.3 Adverse Event Reporting - 7.3.1 In the event of an unanticipated problem or life-threatening complications treating investigators must immediately notify the Overall PI - 7.3.2 Investigators must report to the Overall PI any adverse event (AE) that occurs after the initial dose of study treatment, during treatment,... | [] |
NCT04339062 | 7.3.3 | DF/HCC Adverse Event Reporting Guidelines | 7.3.3 DF/HCC Adverse Event Reporting Guidelines Investigative sites within DF/HCC will report AEs directly to the DFCI Office for Human Research Studies (OHRS) per the DFCI IRB reporting policy.
Serious Adverse Events Definition of SAEs A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:... | [
"Serious Adverse Events"
] |
NCT04339062 | 7.3.4 | Protocol-Specific Adverse Event Reporting Exclusions | 7.3.4 Protocol-Specific Adverse Event Reporting Exclusions There are no protocol-specific adverse event reporting exclusions for this protocol. | [] |
NCT04339062 | 7.4 | Reporting to the Food and Drug Administration (FDA) | 7.4 Reporting to the Food and Drug Administration (FDA) The Overall PI, as study sponsor, will be responsible for all communications with the FDA. The Overall PI will report to the FDA, regardless of the site of occurrence, any serious adverse event that meets the FDA's criteria for expedited reporting following the re... | [] |
NCT04339062 | 7.5 | Reporting to Hospital Risk Management | 7.5 Reporting to Hospital Risk Management Participating investigators will report to their local Risk Management office any participant safety reports, sentinel events or unanticipated problems that require reporting per institutional policy. | [] |
NCT04339062 | 7.6 | Routine Adverse Event Reporting | 7.6 Routine Adverse Event Reporting All Adverse Events must be reported in routine study data submissions to the Overall PI on the toxicity case report forms. AEs reported through expedited processes (e.g., reported to the IRB, FDA, etc.) must also be reported in routine study data submissions. | [] |
NCT04339062 | 7.7 | Routine Adverse Event Reporting to Regeneron | 7.7 Routine Adverse Event Reporting to Regeneron Routine Adverse Events will not be reported to Regeneron. Regeneron will be collecting SAE reports only. All SAEs, whether related or not related to study drug, must be collected, including those thought to be associated with protocol-specified procedures. All SAEs must ... | [
"Serious Adverse Events"
] |
NCT04339062 | 7.6.1 | Acute GVHD Adverse Event Grading (Cohort 1) | 7.6.1 Acute GVHD Adverse Event Grading (Cohort 1) Symptoms of acute GVHD among Cohort 1 require staging at initial and subsequent visits to ensure accuracy of severity. The National Institutes of Health (NIH) consensus criteria use of clinical findings [41], rather than a set of time periods, defines acute vs. chronic ... | [] |
NCT04339062 | 7.6.2 | Diagnostic Criteria for Chronic GVHD (Cohort 1) | 7.6.2 Diagnostic Criteria for Chronic GVHD (Cohort 1) Symptoms of chronic GVHD among Cohort 1 require staging at initial and subsequent visits to ensure accuracy of severity. The National Institutes of Health (NIH) consensus criteria use of clinical findings as summarized in the Table below [42], rather than a set of t... | [] |
NCT04339062 | 7.6.3 | Suspected Acute renal allograft rejection (Cohort 2) | 7.6.3 Suspected Acute renal allograft rejection (Cohort 2) For the purposes of this study, acute renal allograft rejection should be suspected in patients with one or more of the following: ¶ Diagnosis of chronic GVHD requires biopsy or radiology confirmation (or Schirmer test for eyes). - New increase in serum creatin... | [] |
NCT04339062 | 8 | PHARMACEUTICAL INFORMATION | 8. PHARMACEUTICAL INFORMATION A list of the adverse events and potential risks associated with the investigational or other agents administered in this study can be found in Section 7. | [] |
NCT04339062 | 8.1 | Cemiplimab | 8.1 Cemiplimab | [] |
NCT04339062 | 8.1.1 | Description | 8.1.1 Description Cemiplimab is a covalent heterotetramer consisting of two disulfide-link human heavy chains, each of which is covalently bonded through disulfide linkages to a human kappa light chain. The antibody possesses an approximate molecular weight of 143.6 kilounified atomic mass unit (kDa) based on the prima... | [] |
NCT04339062 | 8.1.2 | Form | 8.1.2 Form Solution, Intravenous [preservative free]: Libtayo®: 350 mg/7 mL (7 mL) [contains polysorbate 80]. Clear to opalescent colorless to pale yellow liquid. May contain particles. Protocol Version Date: May 3, 2023 | [] |
NCT04339062 | 8.1.3 | Storage and Stability | 8.1.3 Storage and Stability If stored in a glass front refrigerator, vials should be stored in the carton. Recommended safety measures for preparation and handling of cemiplimab include laboratory coats and gloves. | [] |
NCT04339062 | 8.1.4 | Compatibility | 8.1.4 Compatibility Do not administer with other medications. Flush with NS or D5W at the end of infusion. | [] |
NCT04339062 | 8.1.5 | Handling | 8.1.5 Handling Qualified personnel, familiar with procedures that minimize undue exposure to themselves and the environment, should undertake the preparation, handling, and safe disposal of the chemotherapeutic agent in a self-contained and protective environment. | [] |
NCT04339062 | 8.1.6 | Preparation | 8.1.6 Preparation Cemiplimab-rwlc can be prepared per the package insert which can be referenced at: [https://www.regeneron.com/sites/default/files/Libtayo\\FPI.pdf](https://www.regeneron.com/sites/default/files/LibtayoFPI.pdf) | [] |
NCT04339062 | 8.1.7 | Availability | 8.1.7 Availability Free of cost, investigational supply of cemiplimab, will be provided by Regeneron pharmaceuticals. | [] |
NCT04339062 | 8.1.8 | Ordering | 8.1.8 Ordering Dana-Farber Research Pharmacy and all pharmacies at all participating sites will request supply of cemiplimab, directly from Regeneron, by submitting an order form, provided by Regeneron. | [] |
NCT04339062 | 8.1.9 | Accountability | 8.1.9 Accountability The investigator, or a responsible party designated by the investigator, should maintain a careful record of the inventory and disposition of the agent using the NCI Drug Accountability Record Form (DARF) or another comparable drug accountability form. (See the NCI Investigator's Handbook for Proce... | [] |
NCT04339062 | 8.1.10 | Destruction and Return | 8.1.10 Destruction and Return Unused supplies and expired supplies of the investigational agents will be destroyed on site, by the pharmacy, per institutional standard operating procedures. | [] |
NCT04339062 | 8.2 | Other Agents | 8.2 Other Agents Everolimus or sirolimus (mTOR inhibitors) and prednisone will be stored and prepared per standard of care/institutional guidelines. Everolimus or sirolimus (mTOR inhibitors) and prednisone will be obtained per standard of care clinical supply. | [] |
NCT04339062 | 9 | BIOMARKER, CORRELATIVE, AND SPECIAL STUDIES | 9. BIOMARKER, CORRELATIVE, AND SPECIAL STUDIES | [] |
NCT04339062 | 9.1 | Laboratory Correlative Studies | 9.1 Laboratory Correlative Studies Correlative studies are planned as part of this study in order to characterize the peripheral and tumor immune microenvironment and perform tumor immunophenotyping and functional assays. A peripheral blood sample and fresh tissue tumor biopsy (B1) is required as part of enrollment to ... | [] |
NCT04339062 | 9.1.1 | Specimen Collection and Handling | 9.1.1 Specimen Collection and Handling The study aims for 2-3 cores per mandatory tumor biopsy obtained throughout the study. The tumor biopsy may be core, a fine needle aspiration (FNA), or skin biopsy. If doing a skin core, any size up to 6mm is acceptable. - 1 core is fresh tissue placed in RPMI containing 10% fetal... | [] |
NCT04339062 | 9.1.2 | Planned Correlative Studies | 9.1.2 Planned Correlative Studies Peripheral blood and tumor biopsy samples will be treated with monoclonal antibodies specific for different immune cell markers (CD3, CD8, PD-1/L1, TIM-3, LAG-3, CTLA-4, FOXp3, CD56, etc.) to identify immune cell subsets (or phenotypes) and tumor cells. After incubation of cells with m... | [] |
NCT04339062 | 10 | STUDY CALENDAR | 10. STUDY CALENDAR Baseline or screening evaluations are to be conducted within 2 weeks (14 days, ± 3 days) of the start of protocol therapy (either cemiplimab in Cohort 1, or the lead-in phase for Cohort 2). Baseline imaging must be done 3 | | C3-6 | 3 | C7+3 | End of | Follow-upR | EDCTimepoints | |------------------... | [] |
NCT04339062 | 11 | MEASUREMENT OF EFFECT | 11. MEASUREMENT OF EFFECT | [] |
NCT04339062 | 11.1 | Antitumor Effect – Solid Tumors | 11.1 Antitumor Effect – Solid Tumors For the purposes of this study, participants should be re-evaluated for response every 8 weeks through cycle 10 at which point restaging scans can occur every 12 weeks. In addition to a baseline scan, confirmatory scans should also be obtained (not less than 4) weeks following initi... | [] |
NCT04339062 | 11.1.1 | Definitions | 11.1.1 Definitions Evaluable for Target Disease response. Only those participants who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for target disease response. These participants will have their response cl... | [] |
NCT04339062 | 11.1.2 | Disease Parameters | 11.1.2 Disease Parameters Measurable disease. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, MRI, or calipers by clinical exam. All tumor measurements must be recorded in millimeters (or decimal fractions of ce... | [] |
NCT04339062 | 11.1.3 | Methods for Evaluation of Disease | 11.1.3 Methods for Evaluation of Disease All measurements should be taken and recorded in metric notation using a ruler, calipers, or a digital measurement tool. All baseline evaluations should be performed as closely as possible to the beginning of treatment and never more than 4 weeks before the beginning of the trea... | [] |
NCT04339062 | 11.1.4 | Response Criteria | 11.1.4 Response Criteria | [] |
NCT04339062 | 11.1.4.1 | Evaluation of Target Lesions | 11.1.4.1 Evaluation of Target Lesions Complete Response (CR): Disappearance of all (target) lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference... | [] |
NCT04339062 | 11.1.4.2 | Evaluation of Non-Target Lesions for RECIST v1.1 | 11.1.4.2 Evaluation of Non-Target Lesions for RECIST v1.1 Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of t... | [] |
NCT04339062 | 11.1.4.3 | Evaluation of New Lesions | 11.1.4.3 Evaluation of New Lesions The finding of a new lesion should be unequivocal (i.e. not due to difference in scanning technique, imaging modality, or findings thought to represent something other than tumor (for example, some 'new' bone lesions may be simply healing or flare of pre-existing lesions). However, a ... | [] |
NCT04339062 | 11.1.4.4 | Second Primary Cutaneous and Other Malignancies | 11.1.4.4 Second Primary Cutaneous and Other Malignancies Given this study involves high-risk and immunosuppressed transplant survivors, the finding of a new, spatially or regionally distinct (not in-transit) non-melanomatous skin cancer (squamous cell carcinoma) thought to be a second primary is not considered a new le... | [] |
NCT04339062 | 11.1.4.5 | Treatment Beyond Disease Progression | 11.1.4.5 Treatment Beyond Disease Progression The decision to treat any study participant beyond progression of disease is at the discretion of the treating investigator and can be discussed with the Overall PI. Patients who are assigned a best response of PD at any time point can continue onstudy treatment if the pati... | [] |
NCT04339062 | 11.1.4.6 | Evaluation of Best Overall Response | 11.1.4.6 Evaluation of Best Overall Response The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment w... | [
"For Participants with Non-Measurable Disease (i.e., Non-Target Disease) per RECIST v1.1"
] |
NCT04339062 | 11.1.5 | Duration of Response | 11.1.5 Duration of Response Duration of overall response: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease t... | [] |
NCT04339062 | 11.1.6 | Progression-Free Survival | 11.1.6 Progression-Free Survival Overall Survival: Overall Survival (OS) is defined as the time from registration to death due to any cause, or censored at date last known alive. Progression-Free Survival: Progression-Free Survival (PFS) is defined as the time from registration to the earlier of progression or death du... | [] |
NCT04339062 | 12 | DATA REPORTING / REGULATORY REQUIREMENTS | 12. DATA REPORTING / REGULATORY REQUIREMENTS Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 7.0 (Adverse Events: List and Reporting Requirements). | [] |
NCT04339062 | 12.1 | Data Reporting | 12.1 Data Reporting | [] |
NCT04339062 | 12.1.1 | Method | 12.1.1 Method The Office of Data Quality (ODQ) will collect, manage, and perform quality checks on the data for this study. | [] |
NCT04339062 | 12.1.2 | Responsibility for Data Submission | 12.1.2 Responsibility for Data Submission Study team is responsible for entering data in the eDC system (InForm), within the timeframe, in accordance with DF/HCC SOPs. Tumor genomic and molecular profiling results that are available or become available during the study will be recorded during study participation. | [] |
NCT04339062 | 12.2 | Data Safety Monitoring | 12.2 Data Safety Monitoring The DF/HCC Data and Safety Monitoring Committee (DSMC) will review and monitor toxicity and accrual data from this study. The committee is composed of clinical specialists with experience in oncology and who have no direct relationship with the study. Information that raises any questions ab... | [] |
NCT04339062 | 13 | STATISTICAL CONSIDERATIONS | 13. STATISTICAL CONSIDERATIONS This study is not designed for statistical hypothesis testing.
Original biostatistical design: The 3+3 design is adapted to determine the safety and toxicity of immunotherapy in Cohort 1 and Cohort 2. To that end, while accrual is expected to be slow, we will approve two patients to enro... | [
"Original biostatistical design:"
] |
NCT04339062 | 13.1 | Study Design/Endpoints | 13.1 Study Design/Endpoints Primary Endpoints: To determine the safety and toxicity of immunotherapy in advanced cutaneous squamous cell carcinoma (cSCC) patients having undergone prior hematopoietic stem cell or renal transplant. Secondary Endpoints: To evaluate the anti-tumor activity and survival benefit in advanced... | [] |
NCT04339062 | 13.2 | Stratification Factors | 13.2 Stratification Factors There are no planned stratification factors. | [] |
NCT04339062 | 13.3 | Analysis of Primary Endpoints | 13.3 Analysis of Primary Endpoints Patient safety will be assured by monitoring the proportions of patients who have observed GVHD in Cohort 1 or renal transplant rejection in Cohort 2 when 3 to 12 patients have been enrolled into each cohort. Participants will be evaluable for toxicity from the time of their first tre... | [] |
NCT04339062 | 13.4 | Analysis of Secondary Endpoints | 13.4 Analysis of Secondary Endpoints Time-to-event endpoints will be summarized using the method of Kaplan-Meier. Point estimates for each endpoint will be presented with 90% confidence intervals derived using log(-log(survival)) methodology. The other secondary endpoints including anti-tumor activity will be summarize... | [] |
NCT04339062 | 14 | PUBLICATION PLAN | 14. PUBLICATION PLAN The results should be made public within 24 months of reaching the end of the study. The end of the study is the time point at which the last data items are to be reported, or after the outcome data are sufficiently mature for analysis, as defined in Section 13 on Sample Size, Accrual Rate and Stud... | [
"REFERENCES",
"EPI) EQUATION",
"APPENDIX A CHRONIC KIDNEY DISEASE EPIDEMIOLOGY COLLABORATION (CKD-",
"APPENDIX B PERFORMANCE STATUS CRITERIA",
"APPENDIX C GUIDANCE ON CONTRACEPTION",
"Highly Effective Methods of Contraception:",
"For male subjects with partners that are WOCBP:",
"APPENDIX D IMMUNE-MED... |
NCT04362137 | 1 | Introduction | 1 Introduction | [] |
NCT04362137 | 1.1 | Background | 1.1 Background In December 2019, the Wuhan Municipal Health Committee identified an outbreak of viral pneumonia cases of unknown cause. This outbreak of viral pneumonia was reported to the World Health Organization (WHO) Country Office in China on December 31, 2019. Subsequently, Coronavirus (CoV) RNA was identified in... | [] |
NCT04362137 | 1.1.1 | Ruxolitinib | 1.1.1 Ruxolitinib Ruxolitinib (INCB018424 phosphate, INC424, ruxolitinib phosphate) is a well-established, potent and selective inhibitor of Janus kinase (JAK)1 and JAK2, with modest to marked selectivity against tyrosine kinase (TYK)2 and JAK3, respectively. Ruxolitinib interferes with the signaling of a number of cyt... | [] |
NCT04362137 | 1.1.2 | Additional evidence for CRS and JAK/STAT activation in severe respiratory disease | 1.1.2 Additional evidence for CRS and JAK/STAT activation in severe respiratory disease There is preclinical evidence from both laboratory and animal models that blockade/inhibition of the JAK/STAT pathway could have a beneficial effect on the CRS and the course of severe respiratory disease/ARDS in patients with COVID... | [] |
NCT04362137 | 1.1.2.1 | Laboratory evidence | 1.1.2.1 Laboratory evidence Hermans et al (2020) studied human mast cell lines and demonstrated that ruxolitinib can inhibit mast cell activity, possibly through prevention of STAT5 activation. They postulated that the JAK-STAT pathway is an interesting target for therapy to release symptom burden in mastocytosis and m... | [] |
NCT04362137 | 1.1.2.2 | Animal models | 1.1.2.2 Animal models Zhao et al (2016) looked at LPS-induced lung injury in mice, which models some of the ARDS (e.g. cytokine increases and cell influx) manifestations, as well as an increase in STAT3 expression. STAT3 is downstream of JAK and the authors show that STAT3 inhibition with a tool compound partly inhibit... | [] |
NCT04362137 | 1.1.2.3 | Clinical evidence | 1.1.2.3 Clinical evidence There is clinical evidence of efficacy with ruxolitinib in another recognized disease with CRS: secondary HLH. Two pilot studies of ruxolitinib led to resolution of symptoms and associated laboratory abnormalities in the patients studied; alleviating need for more toxic therapies. (Ahmed 2019;... | [] |
NCT04362137 | 1.1.3 | Background summary | 1.1.3 Background summary It is reasonable to consider the use of ruxolitinib in the treatment of COVID-19 patients with severe respiratory disease because these patients have clinical features consistent with CRS and increased activation of the JAK/STAT pathway (Wang et al 2020; Hermans et al 2020). Moreover, recent li... | [] |
NCT04362137 | 1.2 | Purpose | 1.2 Purpose There are no approved treatments for COVID-19 pneumonia. The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of patients with COVID-19 pneumonia. | [] |
NCT04362137 | 2 | Objectives and endpoints | 2 Objectives and endpoints Table 2-1 Objectives and related endpoints | Table 2-1 | Objectives and related endpoints | | |-------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT04362137 | 4 | Rationale | 4 Rationale | [] |
NCT04362137 | 4.1 | Rationale for study design | 4.1 Rationale for study design This randomized, double-blind, parallel-group, placebo-controlled, design supports the rigorous assessment of efficacy as well as safety of ruxolitinib as add-on to SoC therapy for patients with COVID-19 pneumonia.
Screening Period The screening period allows for assessment of patient en... | [
"Screening Period",
"Study Period"
] |
NCT04362137 | 4.2 | Rationale for choice of background therapy | 4.2 Rationale for choice of background therapy Although there are no approved treatments for COVID-19, SoC therapy for patients with COVID-19 pneumonia generally includes supportive care and anti-viral treatments. Thus, placebo + SoC therapy is appropriate as a control in this study. | [] |
NCT04362137 | 4.3 | Rationale for dose/regimen and duration of treatment | 4.3 Rationale for dose/regimen and duration of treatment The ruxolitinib dose regimen chosen in this study is the lowest efficacious dose based on pharmacokinetic data. Ruxolitinib 5 mg twice daily is the approved starting dose for treatment of steroid-refractory acute graft versus host disease in the US with demonstra... | [] |
NCT04362137 | 4.4 | Rationale for choice of control drugs (comparator/placebo) or combination drugs | 4.4 Rationale for choice of control drugs (comparator/placebo) or combination drugs The study will evaluate the efficacy and safety of oral ruxolitinib + SoC therapy, compared with matching-image placebo + SoC therapy. Despite the lack of targeted treatments for COVID-19, SoC for patients with severe COVID-19 respirato... | [] |
NCT04362137 | 4.5 | Purpose and timing of interim analyses/design adaptations | 4.5 Purpose and timing of interim analyses/design adaptations No interim analysis is planned. An internal Data Monitoring Committee at Novartis will be established to conduct periodic unblinded safety reviews. | [] |
NCT04362137 | 4.6 | Risks and benefits | 4.6 Risks and benefits There is preclinical evidence from both laboratory and animal models that blockade/inhibition of the JAK/STAT pathway could have a beneficial effect on the CRS and the course of severe respiratory disease/ARDS in patients with COVID-19. Additionally, there is some clinical evidence of efficacy wi... | [] |
NCT04362137 | 5 | Study Population | 5 Study Population | [] |
NCT04362137 | 5.1 | Inclusion criteria | 5.1 Inclusion criteria Participants eligible for inclusion in this study must meet all of the following criteria: - 1. Patient or guardian/health proxy must provide informed consent (and assent if applicable) before any study assessment is performed. - 2. Male and female patients aged ≥ 12 years (or ≥ the lower age lim... | [] |
NCT04362137 | 5.2 | Exclusion criteria | 5.2 Exclusion criteria Participants meeting any of the following criteria are not eligible for inclusion in this study. - 1. History of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib. - 2. Presence of severely impaired renal function defined by serum creatinine > 2 mg/dL (>176.8... | [
"OR"
] |
NCT04362137 | 6 | Treatment | 6 Treatment | [] |
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