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NCT03946748

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

Completed Phase 2 Results posted Last updated 26 June 2023
What this trial tests

Phase 2 trial testing REGN3918 in Paroxysmal Nocturnal Hemoglobinuria (PNH) in 24 participants. Completed in 10 June 2021.

Timeline
16 May 2019
Primary endpoint
9 June 2021
10 June 2021

Quick facts

Lead sponsorRegeneron Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsequential
Maskingnone
Primary purposetreatment
Enrollment24
Start date16 May 2019
Primary completion9 June 2021
Estimated completion10 June 2021
Sites12 locations across Hong Kong, Malaysia, United Kingdom, Hungary, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Paroxysmal Nocturnal Hemoglobinuria (PNH). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis Primary · Week 4 through Week 26

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

GroupValue95% CI
REGN391875.057.7 – 92.3
Percentage of Participants Who Achieved Transfusion Avoidance Primary · Up to 26 Weeks

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).

GroupValue95% CI
REGN391887.574.3 – 100.0
Percentage of Participants Who Had Breakthrough Hemolysis (BTH) Secondary · Baseline up to 26 Weeks

Breakthrough hemolysis was defined as the measurement of LDH ≥ 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).

GroupValue95% CI
REGN391800 – 0
Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis Secondary · Week 4 through Week 26

A participant was considered to have achieved normalization of intravascular hemolysis if their LDH readings between Week 4 through Week 26 inclusive had values ≤ 1.0 ULN. A participant must have ≥ 50% of scheduled LDH measures in those weeks, must not have had \> 2 consecutive visits without LDH measures, must not have experienced breakthrough hemolysis, and must not have discontinued study treatment early. A participant was considered not to have achieved normalization of intravascular hemolysis if they failed any of these criteria.

GroupValue95% CI
REGN391816.71.8 – 31.6
Time to First Lactate Dehydrogenase (LDH) ≤1.5 x ULN Secondary · Up to Week 26

A time-to-first-event analysis was used to estimate the proportion of participants achieving transfusion avoidance at Week 26.

GroupValue95% CI
REGN391813.625± 3.6927
Percentage of Days With LDH ≤ 1.5 ULN From Week 4 Through Week 26 Secondary · Week 4 through Week 26

Percentage of days was calculated as number of days with LDH ≤ 1.5 x ULN divided by the participant's total treatment duration (total number of days on treatment from Week 4 through Week 26). LDH ≤ 1.5 x ULN was used as an indicator of adequate control of intravascular hemolysis.

GroupValue95% CI
REGN391893.4± 18.76
Change From Baseline in LDH Levels at Week 26 Secondary · Baseline, Week 26

Change from baseline in LDH levels at Week 26 was reported.

GroupValue95% CI
REGN3918-5.070± 0.1467
Percent Change From Baseline in LDH Levels at Week 26 Secondary · Baseline, Week 26

Percent change from baseline in LDH levels at Week 26 was reported.

GroupValue95% CI
REGN3918-81.72± 1.847
Rate of Transfusion With Red Blood Cells (RBCs) Secondary · Baseline up to Week 26

The rate of transfusion with RBCs for a participant was the total number of transfusions divided by total person-years of time on treatment.

GroupValue95% CI
REGN39181.0390.187 – 5.772
Number of Units of Transfusion With RBCs Secondary · Baseline up to Week 26

Transfusions with RBCs proceeded according to the following predefined criteria that triggered a transfusion; however, the actual number of units to be transfused is at the discretion of the investigator: • Transfuse with RBC(s) if the post-baseline hemoglobin level is \<9 g/dL with symptoms resulting from anemia or • Transfuse with RBC(s) if the post-baseline hemoglobin level is \<7 g/dL.

GroupValue95% CI
REGN39183.625± 4.274
Change From Baseline in RBC Hemoglobin Levels at Week 26 Secondary · Baseline, Week 26

Hemoglobin levels in participants with PNH was measured. Change from baseline in RBC hemoglobin at Week 26 was reported.

GroupValue95% CI
REGN391815.0± 3.24
Change From Baseline in Free Hemoglobin Levels at Week 26 Secondary · Baseline, Week 26

Change from baseline in free hemoglobin levels at Week 26 was assessed.

GroupValue95% CI
REGN3918-9.19± 16.264

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose to Week 26. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

REGN3918
Serious: 0/24 (0%)
Deaths: 0/24
Other adverse events (6 terms — click to expand)

ReactionSystemREGN3918
HeadacheNervous system disorders
Abdominal painGastrointestinal disorders
NasopharyngitisInfections and infestations
Injection site reactionGeneral disorders
NauseaGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations

Data from ClinicalTrials.gov NCT03946748 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2023.
    Kaplon H, Crescioli S, Chenoweth A, Visweswaraiah J, et al · · 2023 · cited 204× · PMID 36472472 · DOI 10.1080/19420862.2022.2153410
  2. How we('ll) treat paroxysmal nocturnal haemoglobinuria: diving into the future.
    Risitano AM, Peffault de Latour R. · · 2022 · cited 48× · PMID 34355382 · DOI 10.1111/bjh.17753
  3. Inhibition of complement pathway activation with Pozelimab, a fully human antibody to complement component C5.
    Latuszek A, Liu Y, Olsen O, Foster R, et al · · 2020 · cited 34× · PMID 32384086 · DOI 10.1371/journal.pone.0231892
  4. Treatment of Rare Inflammatory Kidney Diseases: Drugs Targeting the Terminal Complement Pathway.
    Anliker-Ort M, Dingemanse J, van den Anker J, Kaufmann P. · · 2020 · cited 33× · PMID 33362783 · DOI 10.3389/fimmu.2020.599417
  5. Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Expert Opinion from Central Europe on Special Patient Populations.
    Bodó I, Amine I, Boban A, Bumbea H, et al · · 2023 · cited 15× · PMID 37072660 · DOI 10.1007/s12325-023-02510-4
  6. Pharmacokinetics and pharmacodynamics of pozelimab alone or in combination with cemdisiran in non-human primates.
    Devalaraja-Narashimha K, Huang C, Cao M, Chen YP, et al · · 2022 · cited 15× · PMID 35709087 · DOI 10.1371/journal.pone.0269749
  7. Innovative trial design in precision oncology.
    Tsimberidou AM, Müller P, Ji Y. · · 2022 · cited 14× · PMID 33022355 · DOI 10.1016/j.semcancer.2020.09.006
  8. A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going?
    Griffin M, Kelly R, Pike A. · · 2020 · cited 12× · PMID 37180495 · DOI 10.1177/2633004020959349

Verify or expand the search:

Other trials of REGN3918

Trials testing the same drug.

Other recruiting trials for Paroxysmal Nocturnal Hemoglobinuria (PNH)

Currently open trials in the same condition.

Other Regeneron Pharmaceuticals trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing