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

Phase 3TerminatedNCT04162470

Regeneron Pharmaceuticals24 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Interventions

REGN3918DRUG

Subcutaneous (SC) every week (QW) over the treatment period

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (14)

Regeneron Study Site

Shatin, Hong Kong

Regeneron Study Site

Budapest, Hungary

Regeneron Study Site

Miri, Sarawak, Malaysia

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: Baseline up to Week 26

Secondary Outcomes

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).

Time frame: 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.

Data from ClinicalTrials.gov

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Regeneron Study Site

Sibu, Sarawak, Malaysia

Regeneron Study Site

Kuala Terengganu, Terengganu, Malaysia

Regeneron Study Site

Busan, South Korea

Regeneron Study Site

Seoul, South Korea

Regeneron Study Site

Seoul, South Korea

Regeneron Study Site

Seoul, South Korea

Regeneron Study Site

Seoul, South Korea

...and 4 more locations

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline, Week 26, 78 and 104

Serum Concentrations of Total REGN3918

Serum Concentrations of total REGN3918 was reported.

Time frame: 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).

Time frame: Baseline up to Week 104