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

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

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 Overview

• Status: Terminated
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Drug: REGN3918

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hong Kong
  • Sha Tin, Hong Kong
    • Regeneron Study Site
• Hungary
  • Budapest, Hungary, 1907
    • Regeneron Study Site
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Regeneron Study Site
  • Seoul, Korea, Republic of, 03080
    • Regeneron Study Site
  • Seoul, Korea, Republic of, 03722
    • Regeneron Study Site
  • Seoul, Korea, Republic of, 05030
    • Regeneron Study Site
  • Seoul, Korea, Republic of, 06351
    • Regeneron Study Site
  • Seoul, Korea, Republic of, 07985
    • Regeneron Study Site
• Malaysia
  • Sarawak
    • Miri, Sarawak, Malaysia, 98000
      • Regeneron Study Site
    • Sibu, Sarawak, Malaysia, 96000
      • Regeneron Study Site
  • Terengganu
    • Kuala Terengganu, Terengganu, Malaysia, 20400
      • Regeneron Study Site
• Taiwan
  • Taipei City, Taiwan, 10002
    • Regeneron Study Site
  • Taoyuan City, Taiwan, 333
    • Regeneron Study Site
• United Kingdom
  • Leeds, United Kingdom, LS97TF
    • Regeneron Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2019
• Primary Completion (Actual): April 7, 2022
• Study Completion (Actual): April 7, 2022

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: November 11, 2019
• First Posted (Actual): November 14, 2019

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: May 17, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: PNH
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: R3918-PNH-1868; 2019-000130-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data 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 the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes