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

Phase 3

Terminated

Conditions: Paroxysmal Nocturnal Hemoglobinuria

Interventions: Drug: REGN3918

Registration Number: NCT04162470

Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
REGN3918	REGN3918	Participants who have completed 1 of the 2 parent studies (R3918-PNH-1852 \[NCT03946748\] or R3918-PNH-1853)

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Lactate Dehydrogenase (LDH) Less Than or Equal to (≤) 1.5* ULN From Baseline to Week 26	Baseline up 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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	Baseline up to Week 104	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104	Baseline, Week 26, 78 and 104	Change from baseline in free hemoglobin levels at Week 26, 78 and 104 was reported.
Changes From Baseline in LDH Levels at Week 26, 78, and 104	Baseline, 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.
Percent Change From Baseline in LDH Levels at Week 26, 78, and 104	Baseline, 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.
Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104	Baseline, Week 26, 78, and 104	Change from baseline in RBC hemoglobin levels at Week 26, 78, and 104 was reported.
Percentage of Participants Who Had Breakthrough Hemolysis Through Week 26 and 78	At 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).
Overall Rate of Transfusion With Red Blood Cell (RBCs) Through Week 26	Baseline up to Week 26	The overall rate of transfusion for a participant was calculated based on the duration of treatment exposure of the participant.
Percentage of Participants Who Are Transfusion-free (With RBCs) Through Week 26 and 78	At 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).
Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis Through Week 78	Baseline up to 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.
Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78	Baseline, Week 26 and 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.
Serum Concentrations of Total REGN3918	Pre-dose (Day 1), End of infusion at Week 13, 26, 39, 52, 65, 78, 91 and 104	Serum Concentrations of total REGN3918 was reported.
Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) to REGN3918	Baseline up to Week 104	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).