Trial Outcomes & Findings for REGN3918 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) to Evaluate Its Long Term Safety, Efficacy and Tolerability. (NCT NCT04162470)

NCT ID: NCT04162470

Last Updated: 2023-06-12

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 24 participants
• Primary outcome timeframe: Baseline up to Week 104
• Results posted on: 2023-06-12

Participant Flow

During the study, the sponsor made an administrative decision to terminate the pozelimab monotherapy program, all participants were withdrawn from this study.

Participant milestones

Measure	REGN3918 Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 milligrams (mg) subcutaneous (SC) injection once weekly (QW) for up to 104 weeks.
Overall Study STARTED	24
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	24

Reasons for withdrawal

Measure	REGN3918 Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 milligrams (mg) subcutaneous (SC) injection once weekly (QW) for up to 104 weeks.
Overall Study Withdrawn due to sponsor's decision	24

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	REGN3918 n=24 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Age, Continuous	45.8 Years STANDARD_DEVIATION 17.26 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	21 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 104

Population: SAF included all enrolled participants who received any study drug.

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.

Outcome measures

Measure	REGN3918 n=24 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with TEAEs	15 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Participants with Serious TEAEs	2 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 26

Population: Full Analysis Set (FAS) included all enrolled participants who received any study drug. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	REGN3918 n=23 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Percentage of Participants Who Achieved Lactate Dehydrogenase (LDH) Less Than or Equal to (≤) 1.5* ULN From Baseline to Week 26	95.7 Percentage of participants Interval 87.3 to 100.0

SECONDARY outcome

Timeframe: At Week 26 and 78

Population: FAS included all enrolled participants who received any study drug. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at the specified time points.

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).

Outcome measures

Measure	REGN3918 n=23 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Percentage of Participants Who Had Breakthrough Hemolysis Through Week 26 and 78 At Week 26	0 Percentage of participants Interval 0.0 to 0.0
Percentage of Participants Who Had Breakthrough Hemolysis Through Week 26 and 78 At Week 78	0 Percentage of participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline up to Week 26

Population: FAS included all enrolled participants who received any study drug.

The overall rate of transfusion for a participant was calculated based on the duration of treatment exposure of the participant.

Outcome measures

Measure	REGN3918 n=24 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Overall Rate of Transfusion With Red Blood Cell (RBCs) Through Week 26	0.164 Transfusion per person-year of treatment Interval 0.006 to 4.678

SECONDARY outcome

Timeframe: At Week 26 and 78

Population: FAS included all enrolled participants who received any study drug. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at the specified time points.

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).

Outcome measures

Measure	REGN3918 n=23 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Percentage of Participants Who Are Transfusion-free (With RBCs) Through Week 26 and 78 At Week 26	95.7 Percentage of participants Interval 87.3 to 100.0
Percentage of Participants Who Are Transfusion-free (With RBCs) Through Week 26 and 78 At Week 78	93.8 Percentage of participants Interval 81.9 to 100.0

SECONDARY outcome

Timeframe: Baseline up to Week 78

Population: FAS included all enrolled participants who received any study drug. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.

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.

Outcome measures

Measure	REGN3918 n=16 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Percentage of Participants Who Achieved Adequate Control of Intravascular Hemolysis Through Week 78	93.8 Percentage of participants Interval 81.9 to 100.0

SECONDARY outcome

Timeframe: Baseline, Week 26 and 78

Population: FAS included all enrolled participants who received any study drug. Here, "number analyzed" signifies those participants who were evaluable at the specified time points.

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.

Outcome measures

Measure	REGN3918 n=24 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78 At Week 26	75.0 Percentage of participants Interval 57.7 to 92.3
Percentage of Participants Who Achieved Normalization of Intravascular Hemolysis Through Week 26 and Week 78 At Week 78	55.0 Percentage of participants Interval 33.2 to 76.8

SECONDARY outcome

Timeframe: Baseline, Week 26, 78, and 104

Population: FAS included all enrolled participants who received any study drug. Here, "number analyzed" signifies those participants who were evaluable at the specified time points.

Change from baseline in LDH levels at Week 26, 78, and 104 was reported. Reported baseline is from R3918-PNH-1852 study.

Outcome measures

Measure	REGN3918 n=24 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Changes From Baseline in LDH Levels at Week 26, 78, and 104 At Week 26	-5.098 Units per liter (U/L) Standard Deviation 2.5695
Changes From Baseline in LDH Levels at Week 26, 78, and 104 At Week 78	-5.395 Units per liter (U/L) Standard Deviation 2.8468
Changes From Baseline in LDH Levels at Week 26, 78, and 104 At Week 104	-5.270 Units per liter (U/L) Standard Deviation 2.9057

SECONDARY outcome

Timeframe: Baseline, Week 26, 78, and 104

Population: FAS included all enrolled participants who received any study drug. Here, "number analyzed" signifies those participants who were evaluable at the specified time points.

Percent change from baseline in LDH levels at Week 26, 78, and 104 was reported. Reported baseline is from R3918-PNH-1852 study.

Outcome measures

Measure	REGN3918 n=24 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Percent Change From Baseline in LDH Levels at Week 26, 78, and 104 At Week 26	-81.900 Percent change Standard Deviation 8.9226
Percent Change From Baseline in LDH Levels at Week 26, 78, and 104 At Week 78	-84.256 Percent change Standard Deviation 8.1412
Percent Change From Baseline in LDH Levels at Week 26, 78, and 104 At Week 104	-83.930 Percent change Standard Deviation 7.6705

SECONDARY outcome

Timeframe: Baseline, Week 26, 78, and 104

Population: FAS included all enrolled participants who received any study drug. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at the specified time points.

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

Outcome measures

Measure	REGN3918 n=21 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104 At Week 26	3.6 Gram per liter (g/l) Standard Deviation 8.97
Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104 At Week 78	5.3 Gram per liter (g/l) Standard Deviation 17.20
Change From Baseline in Red Blood Cell (RBC) Hemoglobin Levels at Week 26, 78, and 104 At Week 104	-2.4 Gram per liter (g/l) Standard Deviation 16.56

SECONDARY outcome

Timeframe: Baseline, Week 26, 78 and 104

Population: FAS included all enrolled participants who received any study drug. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at the specified time points.

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

Outcome measures

Measure	REGN3918 n=16 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104 At Week 78	-0.56 Milligram per deciliter (mg/dL) Standard Deviation 2.196
Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104 At Week 104	-0.93 Milligram per deciliter (mg/dL) Standard Deviation 1.153
Change From Baseline in Free Hemoglobin Levels at Week 26, 78 and 104 At Week 26	-1.39 Milligram per deciliter (mg/dL) Standard Deviation 6.929

SECONDARY outcome

Timeframe: Pre-dose (Day 1), End of infusion at Week 13, 26, 39, 52, 65, 78, 91 and 104

Population: Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at the specified time points.

Serum Concentrations of total REGN3918 was reported.

Outcome measures

Measure	REGN3918 n=23 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Serum Concentrations of Total REGN3918 Pre-dose (Day 1)	423 Milligrams per liter (mg/L) Standard Deviation 218
Serum Concentrations of Total REGN3918 Week 13	398 Milligrams per liter (mg/L) Standard Deviation 203
Serum Concentrations of Total REGN3918 Week 26	401 Milligrams per liter (mg/L) Standard Deviation 212
Serum Concentrations of Total REGN3918 Week 39	420 Milligrams per liter (mg/L) Standard Deviation 216
Serum Concentrations of Total REGN3918 Week 52	413 Milligrams per liter (mg/L) Standard Deviation 202
Serum Concentrations of Total REGN3918 Week 65	438 Milligrams per liter (mg/L) Standard Deviation 207
Serum Concentrations of Total REGN3918 Week 78	433 Milligrams per liter (mg/L) Standard Deviation 266
Serum Concentrations of Total REGN3918 Week 91	483 Milligrams per liter (mg/L) Standard Deviation 278

SECONDARY outcome

Timeframe: Baseline up to Week 104

Population: Here, "number analyzed" signifies those participants who were evaluable at the specified time points.

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).

Outcome measures

Measure	REGN3918 n=21 Participants Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) to REGN3918	0 Participants

Adverse Events

REGN3918

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	REGN3918 n=24 participants at risk Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Gastrointestinal disorders Abdominal pain	4.2% 1/24 • Number of events 1 • From first dose to Week 104
Infections and infestations Influenza	4.2% 1/24 • Number of events 1 • From first dose to Week 104
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	4.2% 1/24 • Number of events 1 • From first dose to Week 104

Other adverse events

Measure	REGN3918 n=24 participants at risk Participants who completed parent study R3918-PNH-1852 (NCT03946748) received pozelimab 800 mg SC injection QW for up to 104 weeks.
Gastrointestinal disorders Mouth ulceration	8.3% 2/24 • Number of events 2 • From first dose to Week 104
General disorders Chills	8.3% 2/24 • Number of events 2 • From first dose to Week 104
Nervous system disorders Headache	8.3% 2/24 • Number of events 2 • From first dose to Week 104
Skin and subcutaneous tissue disorders Rash	8.3% 2/24 • Number of events 2 • From first dose to Week 104

Additional Information

Clinical Trials Administrator

Regeneron Pharmaceuticals, Inc

Phone: 844-734-6643

Email: clinicaltrials@regeneron.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator has the right to independently publish study results from the investigator's site after a multi-center publication, or a defined period after the completion of the study by all sites. The investigator must provide the sponsor a copy of any such publication derived from the study for review and comment in advance of any submission, and delay publication, if requested, to allow the Sponsor to preserve its proprietary rights.
• Publication restrictions are in place

Restriction type: OTHER