REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate Its Long Term Safety, Efficacy and Tolerability.

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the long-term safety, tolerability, and effect on intravascular hemolysis of REGN3918 in patients with paroxysmal nocturnal hemoglobinuria (PNH). The secondary objectives of the study are: To evaluate the long-term effect of REGN3918 on intravascular hemolysis To assess the concentrations of total REGN3918 in serum To evaluate the occurrence of the immunogenicity of REGN3918

Official Title
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An Open-label Extension Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria

Conditions
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Paroxysmal Nocturnal Hemoglobinuria

Intervention / Treatment
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* Drug: REGN3918


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: • Patients with PNH who have completed, without discontinuation, study treatment in one of the parent studies in which they participated (either R3918-PNH-1852 [NCT03946748] or R3918-PNH-1853) Key Exclusion Criteria: Significant protocol deviation(s) in the parent study based on the investigator's judgment and to the extent that these would (if continued) impact the study objectives and/or safety of the patient (for example, repetitive non-compliance with dosing by the patient) Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in or completing the study NOTE: Other protocol defined exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN3918<br>Participants who have completed 1 of the 2 parent studies (R3918-PNH-1852 [NCT03946748] or R3918-PNH-1853) | Drug: REGN3918<br>* Subcutaneous (SC) every week (QW) over the treatment period<br>* Other names: Pozelimab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TEAEs was defined as AEs that developed or worsened during the on-treatment period. SAE was defined as any untoward medical occurrence that resulted in any of following outcomes: death, life-threatening, required initial/prolonged in-participant hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect/considered as medically important event. TEAEs included both Serious TEAEs and non-serious TEAEs. | Baseline up to Week 104 | 
| Percentage of Participants Who Achieved Lactate Dehydrogenase (LDH) Less Than or Equal to (≤) 1.5* ULN From Baseline to Week 26 | Percentage of participants who achieved LDH ≤1.5* Upper limit of normal (ULN) over Week 26, defined as LDH ≤1.5*ULN from baseline up to Week 26 were reported. A participant was considered to have met the criteria for adequate control of intravascular hemolysis if all of their LDH readings from the baseline through Week 26 inclusive or through the analysis end date, whichever is earlier, had values ≤ 1.5*ULN. | Baseline up to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Had Breakthrough Hemolysis Through Week 26 and 78 | A participant was considered to have breakthrough hemolysis if he/she had any LDH measurement greater than or equal to (≥) 2*ULN, concomitant with associated signs or symptoms at any time subsequent to an initial achievement of disease control (i.e., LDH ≤ 1.5* ULN). | At Week 26 and 78 | 
| Overall Rate of Transfusion With Red Blood Cell (RBCs) Through Week 26 | The overall rate of transfusion for a participant was calculated based on the duration of treatment exposure of the participant. | Baseline up to Week 26 | 
| Percentage of Participants Who Are Transfusion-free (With RBCs) Through Week 26 and 78 | Transfusion free was defined as not having received an RBC transfusion during the first 26 and 78 weeks. A transfusion was counted only if it was per-protocol, that is, if it follows the predefined transfusion algorithm: RBC transfusion due to a post-baseline hemoglobin level less than (<) 9 gram per deciliter (g/dL) (with anemia symptoms) or a post-baseline hemoglobin level < 7 g/dL (without anemia symptoms). | At Week 26 and 78 | 
| Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis Through Week 78 | A participant was considered to have met the criteria for adequate control of intravascular hemolysis if all of his/her LDH readings from the baseline through Week 78 inclusive or through the analysis end date, whichever is earlier, had values <=1.5* ULN. and must not have discontinued study treatment early. | Baseline up to Week 78 | 
| Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78 | A participant was considered to have met normalization of intravascular hemolysis if all of their LDH readings from the baseline through Week 26 or 78 inclusive, or through the analysis end date, whichever is earlier, had values ≤ 1.0*ULN. | Baseline, Week 26 and 78 | 
| Changes From Baseline in LDH Levels at Week 26, 78, and 104 | Change from baseline in LDH levels at Week 26, 78, and 104 was reported. Reported baseline is from R3918-PNH-1852 study. | Baseline, Week 26, 78, and 104 | 
| Percent Change From Baseline in LDH Levels at Week 26, 78, and 104 | Percent change from baseline in LDH levels at Week 26, 78, and 104 was reported. Reported baseline is from R3918-PNH-1852 study. | Baseline, Week 26, 78, and 104 | 
| Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104 | Change from baseline in RBC hemoglobin levels at Week 26, 78, and 104 was reported. | Baseline, Week 26, 78, and 104 | 
| Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104 | Change from baseline in free hemoglobin levels at Week 26, 78 and 104 was reported. | Baseline, Week 26, 78 and 104 | 
| Serum Concentrations of Total REGN3918 | Serum Concentrations of total REGN3918 was reported. | Pre-dose (Day 1), End of infusion at Week 13, 26, 39, 52, 65, 78, 91 and 104 | 
| Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) to REGN3918 | Number of Participants with treatment-emergent ADA response to REGN3918 was reported. The ADA analysis set (AAS) includes all treated participants who received any amount of study drug (active [SAF]) and had at least 1 non missing anti pozelimab antibody result following the first dose of study drug. The AAS is based on the actual treatment received (as treated). | Baseline up to Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PNH