Study to Evaluate the Efficacy and Safety of REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

NCT03946748 | Completed Phase 2 Results

• 2 other identifiers: R3918-PNH-18522018-002734-20
• Study Type: interventional
• Target: 24
• Locations: 5 countries
• Sites: 12

Brief Summary

The primary objective of the study is to demonstrate a reduction in intravascular hemolysis by REGN3918 over 26 weeks of treatment in patients with active PNH who are treatment-naive to complement inhibitor therapy or have not recently received complement inhibitor therapy. The secondary objectives of the study are:

• To evaluate the safety and tolerability of REGN3918.
• To evaluate the effect of REGN3918 on parameters of intravascular hemolysis
• To assess the concentrations of total REGN3918 in serum.
• To evaluate the incidence of treatment-emergent anti-drug antibodies to REGN3918 over time
• To evaluate the effect of REGN3918 on patient-reported outcomes (PROs) measuring fatigue and health-related quality of life

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis

  Participants were considered to have had adequate control of intravascular hemolysis if all of their lactose dehydrogenase (LDH) readings from Week 4 through Week 26 inclusive had values less than or equal to ≤ 1.5 × upper limit of normal (ULN). Participants must have greater than or equal to (≥) 50 percent (%) of scheduled LDH measures in those weeks, must not have had more than (\>) 2 consecutive visits without LDH measures, must not have experienced breakthrough hemolysis, and must not have discontinued study treatment early. Participants were considered not to have had adequate control of intravascular hemolysis if they failed any of these criteria.

  Week 4 through Week 26

• Percentage of Participants Who Achieved Transfusion Avoidance

  Transfusion avoidance was defined as not having received red blood cell (RBC) transfusion during the first 26 weeks. A transfusion was counted only if it was per-protocol, that is, it followed the predefined transfusion algorithm: RBC transfusion due to a post-baseline hemoglobin level \< 9 grams per deciliter (g/dL) (with anemia symptoms) or a post-baseline hemoglobin level \< 7 g/dL (without anemia symptoms).

  Up to 26 Weeks

Secondary Outcomes (23)

• Percentage of Participants Who Had Breakthrough Hemolysis (BTH)

  Baseline up to 26 Weeks

• Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis

  Week 4 through Week 26

• Time to First Lactate Dehydrogenase (LDH) ≤1.5 x ULN

  Up to Week 26

• Percentage of Days With LDH ≤ 1.5 ULN From Week 4 Through Week 26

  Week 4 through Week 26

• Change From Baseline in LDH Levels at Week 26

  Baseline, Week 26

Study Arms (1)

REGN3918

EXPERIMENTAL

Cohort A (Dose Confirmation) If a decision is made to expand Cohort A, patients will be assigned to Cohort A. Cohort B (Dose Expansion) If a decision is made to progress to Cohort B, patients will be assigned to Cohort B.

Drug: REGN3918

Interventions

REGN3918 DRUG

Single intravenous (IV) dose, then a subcutaneous (SC) dose once weekly (QW).

REGN3918

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) confirmed by high-sensitivity flow cytometry
• PNH granulocytes \> 10% at screening visit
• Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms (eg, fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \<10 g/dL\], history of a MAVE \[including thrombosis\], dysphagia, or erectile dysfunction) or history of red blood cell (RBC) transfusion due to PNH within 3 months of screening.
• Lactate dehydrogenase (LDH) level ≥ 2 × upper limit of normal (ULN) at screening visit.

You may not qualify if:

• Prior treatment with a complement inhibitor either within 6 months prior to screening visit or at any time where the patient was refractory to complement inhibitor therapy, in the opinion of the investigator (with the exception of eculizumab refractory patients due to the C5 variant R885H/C)
• History of bone marrow transplantation
• Body weight \< 40 kilograms at screening visit
• Peripheral blood absolute neutrophil count (ANC) \<500/μL \[\<0.5 x 109/L\] or peripheral blood platelet count \<50,000/μL
• Documented history of systemic fungal disease or unresolved tuberculosis, or evidence of active or latent tuberculosis infection (LTBI) during screening period
• Any contraindication for receiving Neisseria meningitidis vaccination and antibiotic prophylaxis therapy as recommended in the study
• Any active, ongoing infection within 2 weeks of screening or during the screening period
• Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases, or patients with short life expectancy
• Women who are pregnant, breastfeeding, or who have a positive pregnancy test at screening visit or day 1

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (12)

Regeneron Study Site

Shatin, Hong Kong

Location

Regeneron Study Site

Budapest, 1083, Hungary

Location

Regeneron Study Site

Kaposvár, 4400, Hungary

Location

Regeneron Study Site

Kota Bharu, Kelantan, 15586, Malaysia

Location

Regeneron Study Site

Sibu, Sarawak, 96000, Malaysia

Location

Regeneron Study Site

Kuala Terengganu, Terengganu, 20400, Malaysia

Location

Regeneron Study Site

Seoul, 03080, South Korea

Location

Regeneron Study Site

Seoul, 03722, South Korea

Location

Regeneron Study Site

Seoul, 05030, South Korea

Location

Regeneron Study Site

Seoul, 06351, South Korea

Location

Regeneron Study Site

Seoul, 07985, South Korea

Location

Regeneron Study Site

Airdrie, Lanarkshire, ML60JS, United Kingdom

Location

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2019
• First Posted: May 13, 2019
• Study Start: May 16, 2019
• Primary Completion: June 9, 2021
• Study Completion: June 10, 2021
• Last Updated: June 26, 2023
• Results First Posted: June 26, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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).

Locations

HK (1); HU (2); KR (5); MY (3); GB (1)