April 6, 2022
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April 29, 2022
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February 22, 2024
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July 14, 2022
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March 3, 2026 (Final data collection date for primary outcome measure)
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Progression-free survival (PFS) [ Time Frame: Approximately 27 months ] per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on Blinded Independent Central Review (BICR)
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- PFS [ Time Frame: Up to 27 months ]
Per RECIST 1.1 based on BICR or investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)
- Overall survival (OS) [ Time Frame: Up to 96 months ]
- ORR [ Time Frame: Up to 27 months ]
Per RECIST 1.1 based on BICR or investigator assessment according to RECIST 1.1 and iRECIST
- Disease control rate (DCR) [ Time Frame: Up to 27 months ]
Per RECIST 1.1 based on BICR or investigator assessment according to RECIST 1.1 and iRECIST
- Duration of response (DoR) [ Time Frame: Up to 27 months ]
Per RECIST 1.1 based on BICR or investigator assessment according to RECIST 1.1 and iRECIST
- Incidence of Adverse Events (AEs) [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
Including treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and/ or immune-related adverse event (imAEs)
- Occurrence of interruption and discontinuation of study drug(s) due to AEs [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
Including TEAEs, AESIs, and/ or imAEs
- Incidence of deaths related to TEAEs [ Time Frame: Up to 6 years ]
- Incidence of laboratory abnormalities [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
Will be graded using the current version of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system (version 5.0)
- Concentrations of cemiplimab in serum [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
- Concentrations of fianlimab in serum [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
- Incidence of anti-drug antibodies (ADA) to fianlimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Titer of anti-drug antibodies (ADA) to fianlimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Incidence of ADA to cemiplimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Titer of ADA to cemiplimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Incidence of neutralizing antibodies (NAb) to fianlimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Incidence of NAb to cemiplimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Patient-reported outcomes (PROs) as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
EORTC-QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- PROs as measured by EQ-5D-5L [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction.
- PROs as measured by Functional Assessment of Cancer Therapy melanoma (FACTM) (melanoma subscale only) [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
The FACTM is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G). The FACTM is scored on a 5 point Likert-scale: "Not at all", "A little bit", "Somewhat", "Quite a bit", and "Very much.". A Higher score represents higher Health Related Quality of Life (HRQoL).
- PROs as measured by Patient Global Impression of Severity (PGIS) [ Time Frame: Up to 21 days post last dose, approximately 6 years ]
The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe".
- PROs as measured by Patient Global Impression of Change (PGIC) [ Time Frame: Up to 21 days post last dose, approximately 6 years ]
The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change"
- Change in physical functioning per EORTC QLQ-C30 [ Time Frame: Baseline to Week 25 ]
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- Change in role functioning per EORTC QLQ-C30 [ Time Frame: Baseline to Week 25 ]
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- Change in global health status/quality of life (GHS/QoL) per EORTC QLQ-C30 [ Time Frame: Baseline to Week 25 ]
Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- Change in physical functioning per EORTC QLQ-C30 [ Time Frame: Baseline to end of study, approximately 6 years ]
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- Change in role functioning per EORTC QLQ-C30 [ Time Frame: Baseline to end of study, approximately 6 years ]
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- Change in GHS/QoL per EORTC QLQ-C30 [ Time Frame: Baseline to end of study, approximately 6 years ]
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
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- Overall survival (OS) [ Time Frame: Up to 96 months ]
- Objective response rate (ORR) [ Time Frame: Up to 27 months ]
per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on Blinded Independent Central Review (BICR) or based on investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)
- Disease control rate (DCR) [ Time Frame: Up to 27 months ]
per RECIST 1.1 based on BICR or based on investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)
- Duration of response (DoR) [ Time Frame: Up to 27 months ]
per RECIST 1.1 via BICR or based on investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)
- PFS [ Time Frame: Up to 27 months ]
Based on investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)
- Incidence of Adverse Events (AEs) [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
Including treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and/ or immune-related adverse event (irAEs)
- Occurrence of interruption and discontinuation of study drug(s) due to AEs [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
Including TEAEs, AESIs, and/ or irAEs
- Incidence of deaths [ Time Frame: Up to 6 years ]
- Incidence of laboratory abnormalities [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
Will be graded using the current version of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system (version 5.0)
- Concentrations of cemiplimab in serum [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
- Concentrations of fianlimab in serum [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
- Incidence of anti-drug antibodies (ADA) to fianlimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Titer of anti-drug antibodies (ADA) to fianlimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Incidence of ADA to cemiplimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Titer of ADA to cemiplimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Incidence of neutralizing antibodies (NAb) to fianlimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Incidence of NAb to cemiplimab over time [ Time Frame: Up to 30 days post last dose, approximately 6 years ]
- Patient-reported outcomes (PROs) as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
EORTC-QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- PROs as measured by EQ-5D-5L [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction.
- PROs as measured by Functional Assessment of Cancer Therapy (FACT)-melanoma (melanoma subscale only) [ Time Frame: Up to 90 days post last dose, approximately 6 years ]
The FACT-M is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G). The FACT-M is scored on a 5 point Likert-scale: "Not at all", "A little bit", "Somewhat", "Quite a bit", and "Very much.". A Higher score represents higher Health Related Quality of Life (HRQoL).
- PROs as measured by Patient Global Impression of Severity (PGIS) [ Time Frame: Up to 21 days post last dose, approximately 6 years ]
The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe".
- PROs as measured by Patient Global Impression of Change (PGIC) [ Time Frame: Up to 21 days post last dose, approximately 6 years ]
The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change"
- Change in physical functioning per EORTC QLQ-C30 [ Time Frame: Baseline to Week 25 ]
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- Change in role functioning per EORTC QLQ-C30 [ Time Frame: Baseline to Week 25 ]
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- Change in global health status/quality of life (GHS/QoL) per EORTC QLQ-C30 [ Time Frame: Baseline to Week 25 ]
Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- Change in physical functioning per EORTC QLQ-C30 [ Time Frame: Baseline to end of study, approximately 6 years ]
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- Change in role functioning per EORTC QLQ-C30 [ Time Frame: Baseline to end of study, approximately 6 years ]
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
- Change in GHS/QoL per EORTC QLQ-C30 [ Time Frame: Baseline to end of study, approximately 6 years ]
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.
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Not Provided
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Not Provided
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Clinical Study of Fianlimab in Combination With Cemiplimab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma
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A Phase 2 and Phase 3 Trial of Fianlimab (REGN3767, Anti-LAG-3) + Cemiplimab Versus Pembrolizumab in Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma
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This study is researching an experimental drug called REGN3767, also known as fianlimab (R3767), when combined with another medication called REGN2810, also known as cemiplimab (each individually called a "study drug" or called "study drugs" when combined). The study is focused on patients with a type of skin cancer known as melanoma.
The aims of the study are to see how effective the combination of fianlimab and cemiplimab are in treating the melanoma skin cancer, in comparison with a medication, pembrolizumab, approved for the treatment of melanoma skin cancer in adults, and to observe any similarities, or differences, in how the study drugs work in adolescent participants compared with adult participants.
The study is looking at several other research questions, including:
- What side effects may happen from receiving the study drugs
- How much study drug is in the blood at different times
- Whether the body makes antibodies against the study drugs (which could make the drugs less effective or could lead to side effects). Antibodies are proteins that are naturally found in the blood stream that fight infections.
- How administering the study drugs might improve quality of life
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Not Provided
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Interventional
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Phase 2 Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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Melanoma
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Not Provided
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Recruiting
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1925
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1100
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August 31, 2032
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March 3, 2026 (Final data collection date for primary outcome measure)
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Key Inclusion Criteria:
- Age ≥12 years on the date of providing informed consent
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Patients with histologically confirmed unresectable Stage III and Stage IV (metastatic) melanoma (AJCC, 8th revised edition) who have not received prior systemic therapy for advanced unresectable disease
- Patients who received adjuvant and/or neoadjuvant systemic therapies are eligible if they did not have evidence of progression or recurrence of disease and/or discontinued due to occurrence of unmanageable imAEs ≥ grade 3 (with the exclusion of endocrinopathies which are fully controlled by hormone replacement) while on such therapies. Also, patients must have had a treatment-free and disease-free interval of >6 months. Accrual of these patients is limited to approximately 10% of the total population enrolled in each of the Phase 2 and Phase 3 parts of the study.
- Patients with acral and mucosal melanomas are eligible. Combined accrual will be limited to 10% of the total population enrolled in the Phase 3 part of the study.
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Measurable disease per RECIST v1.1
- Previously irradiated lesions can only be counted as target lesions if they have been demonstrated to progress and no other target lesion is available
- Cutaneous lesions should be evaluated as non-target lesions
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Performance status:
- For adult patients: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- For pediatric patients: Karnofsky performance status ≥70 (patients ≥16 years) or Lansky performance status ≥70 (patients ≤16 years)
- Anticipated life expectancy of at least 3 months
Key Exclusion Criteria:
- Uveal melanoma
- Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.
- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection
- Unknown v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation status as described in the protocol
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Systemic immune suppression:
- Use of immunosuppressive doses of corticosteroids (>10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication. Physiologic replacement doses are allowed up to and including 10mg of prednisone/day or equivalent. Inhaled or topical steroids are permitted, if they are not for treatment of an autoimmune disorder.
- Other clinically relevant forms of systemic immune suppression
- Treatment with other anti-cancer therapy including immuno- therapy, chemotherapy, major surgery or biological therapy within 21 days prior to the first dose of trial treatment. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed.
- History or current evidence of significant (CTCAE Grade ≥2) local or systemic infection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 14 days prior to the first dose of trial medication.
- Participants with a history of myocarditis.
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Active or untreated brain metastases or spinal cord compression. Patients with leptomeningeal disease are excluded. Patients with known brain metastases are eligible if they:
- Received radiotherapy or another appropriate standard therapy for the brain metastases,
- Have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment) for at least 14 days prior to enrollment
- Did not require immunosuppressive doses of corticosteroids therapy (>10mg of prednisone per day or equivalent) in the 14 days prior to enrollment
- Are asymptomatic with a single untreated brain metastasis <10 mm in size
Note: Other protocol-defined Inclusion/ Exclusion criteria apply
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Sexes Eligible for Study: |
All |
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12 Years and older (Child, Adult, Older Adult)
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No
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Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, France, Georgia, Germany, Hungary, Ireland, Italy, Mexico, Netherlands, Peru, Poland, Romania, South Africa, Spain, Turkey, United Kingdom, United States
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NCT05352672
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R3767-ONC-2011 2021-004453-23 ( EudraCT Number ) 2023-505772-30-00 ( Registry Identifier: EUCT Number )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Yes |
Plan Description: |
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing |
Supporting Materials: |
Study Protocol |
Supporting Materials: |
Statistical Analysis Plan (SAP) |
Supporting Materials: |
Informed Consent Form (ICF) |
Supporting Materials: |
Clinical Study Report (CSR) |
Supporting Materials: |
Analytic Code |
Time Frame: |
When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy. |
Access Criteria: |
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf |
URL: |
https://vivli.org/ |
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Regeneron Pharmaceuticals
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Same as current
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Regeneron Pharmaceuticals
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Same as current
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Not Provided
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Study Director: |
Clinical Trial Management |
Regeneron Pharmaceuticals |
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Regeneron Pharmaceuticals
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February 2024
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