NCT04162470

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

Terminated Phase 3 Results posted Last updated 12 June 2023

What this trial tests

Phase 3 trial testing REGN3918 in Paroxysmal Nocturnal Hemoglobinuria in 24 participants. Terminated before completion.

Timeline

3 December 2019

Primary endpoint
7 April 2022

7 April 2022

Quick facts

Lead sponsor	Regeneron Pharmaceuticals
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	24
Start date	3 December 2019
Primary completion	7 April 2022
Estimated completion	7 April 2022
Sites	14 locations across Hong Kong, Malaysia, Taiwan, United Kingdom, Hungary, South Korea

Drugs / interventions tested

• REGN3918 — full drug profile →

Conditions studied

• Paroxysmal Nocturnal Hemoglobinuria — all drugs for Paroxysmal Nocturnal Hemoglobinuria →

Sponsor

Regeneron Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Paroxysmal Nocturnal Hemoglobinuria. 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.

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Primary · 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

Participants with TEAEs

Group	Value	95% CI
REGN3918	15

Participants with Serious TEAEs

Group	Value	95% CI
REGN3918	2

Percentage of Participants Who Achieved Lactate Dehydrogenase (LDH) Less Than or Equal to (≤) 1.5* ULN From Baseline to Week 26 Primary · 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.

Group	Value	95% CI
REGN3918	95.7	87.3 – 100.0

Percentage of Participants Who Had Breakthrough Hemolysis Through Week 26 and 78 Secondary · 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).

At Week 26

Group	Value	95% CI
REGN3918	0	0 – 0

At Week 78

Group	Value	95% CI
REGN3918	0	0 – 0

Overall Rate of Transfusion With Red Blood Cell (RBCs) Through Week 26 Secondary · 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.

Group	Value	95% CI
REGN3918	0.164	0.006 – 4.678

Percentage of Participants Who Are Transfusion-free (With RBCs) Through Week 26 and 78 Secondary · 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).

At Week 26

Group	Value	95% CI
REGN3918	95.7	87.3 – 100.0

At Week 78

Group	Value	95% CI
REGN3918	93.8	81.9 – 100.0

Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis Through Week 78 Secondary · 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.

Group	Value	95% CI
REGN3918	93.8	81.9 – 100.0

Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78 Secondary · 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.

At Week 26

Group	Value	95% CI
REGN3918	75.0	57.7 – 92.3

At Week 78

Group	Value	95% CI
REGN3918	55.0	33.2 – 76.8

Changes From Baseline in LDH Levels at Week 26, 78, and 104 Secondary · 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.

At Week 26

Group	Value	95% CI
REGN3918	-5.098	± 2.5695

At Week 78

Group	Value	95% CI
REGN3918	-5.395	± 2.8468

At Week 104

Group	Value	95% CI
REGN3918	-5.270	± 2.9057

Percent Change From Baseline in LDH Levels at Week 26, 78, and 104 Secondary · 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.

At Week 26

Group	Value	95% CI
REGN3918	-81.900	± 8.9226

At Week 78

Group	Value	95% CI
REGN3918	-84.256	± 8.1412

At Week 104

Group	Value	95% CI
REGN3918	-83.930	± 7.6705

Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104 Secondary · Baseline, Week 26, 78, and 104

Change from baseline in RBC hemoglobin levels at Week 26, 78, and 104 was reported.

At Week 26

Group	Value	95% CI
REGN3918	3.6	± 8.97

At Week 78

Group	Value	95% CI
REGN3918	5.3	± 17.20

At Week 104

Group	Value	95% CI
REGN3918	-2.4	± 16.56

Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104 Secondary · Baseline, Week 26, 78 and 104

Change from baseline in free hemoglobin levels at Week 26, 78 and 104 was reported.

At Week 26

Group	Value	95% CI
REGN3918	-1.39	± 6.929

At Week 78

Group	Value	95% CI
REGN3918	-0.56	± 2.196

At Week 104

Group	Value	95% CI
REGN3918	-0.93	± 1.153

Serum Concentrations of Total REGN3918 Secondary · 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.

Pre-dose (Day 1)

Group	Value	95% CI
REGN3918	423	± 218

Week 13

Group	Value	95% CI
REGN3918	398	± 203

Week 26

Group	Value	95% CI
REGN3918	401	± 212

Week 39

Group	Value	95% CI
REGN3918	420	± 216

Week 52

Group	Value	95% CI
REGN3918	413	± 202

Week 65

Group	Value	95% CI
REGN3918	438	± 207

Week 78

Group	Value	95% CI
REGN3918	433	± 266

Week 91

Group	Value	95% CI
REGN3918	483	± 278

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose to Week 104. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

REGN3918

Serious: 2/24 (8%)

Deaths: 0/24

Serious adverse events (3 terms)

Reaction	System	REGN3918
Abdominal pain	Gastrointestinal disorders	—
Influenza	Infections and infestations	—
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—

Other adverse events (4 terms — click to expand)

Reaction	System	REGN3918
Mouth ulceration	Gastrointestinal disorders	—
Chills	General disorders	—
Headache	Nervous system disorders	—
Rash	Skin and subcutaneous tissue disorders	—

Most-reported serious reactions: Abdominal pain, Influenza, Uterine leiomyoma.

Data from ClinicalTrials.gov NCT04162470 adverse events section.

Sponsor's own description

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

Publications & conference data

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

1. Antibodies to watch in 2021.
   Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
2. 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
3. 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
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. Current Opinions on the Clinical Utility of Ravulizumab for the Treatment of Paroxysmal Nocturnal Hemoglobinuria.
   Gurnari C, Nautiyal I, Pagliuca S. · · 2021 · cited 5× · PMID 34934322 · DOI 10.2147/tcrm.s273360
6. Safety, Efficacy, and Patient-Reported Outcomes From a Phase 2 Randomized Trial of Pozelimab and Cemdisiran Combination in Patients With Paroxysmal Nocturnal Hemoglobinuria.
   Jang JH, Wong RSM, Hartford C, Pavani R, et al · · 2025 · PMID 40708708 · DOI 10.1002/jha2.70095
7. P775: LONG-TERM EFFICACY AND SAFETY OF POZELIMAB MONOTHERAPY IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
   Jang J, Wong R, Weyne J, Chaudhari U, et al · · 2023