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

Back to results

Primary Purpose

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

REGN3918

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria focused on measuring PNH

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

REGN3918

Arm Description

Participants who have completed 1 of the 2 parent studies (R3918-PNH-1852 [NCT03946748] or R3918-PNH-1853)

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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).

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.

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).

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.

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.

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.

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.

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.

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.

Serum Concentrations of Total REGN3918

Serum Concentrations of total REGN3918 was reported.

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).

Full Information

NCT ID

NCT04162470

First Posted

November 11, 2019

Last Updated

May 17, 2023

Sponsor

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04162470

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Terminated

Why Stopped

Business Decision

Study Start Date

December 3, 2019 (Actual)

Primary Completion Date

April 7, 2022 (Actual)

Study Completion Date

April 7, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Regeneron Pharmaceuticals

4. Oversight

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

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Paroxysmal Nocturnal Hemoglobinuria

Keywords

PNH

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

REGN3918

Arm Type

Experimental

Arm Description

Participants who have completed 1 of the 2 parent studies (R3918-PNH-1852 [NCT03946748] or R3918-PNH-1853)

Intervention Type

Drug

Intervention Name(s)

REGN3918

Other Intervention Name(s)

Pozelimab

Intervention Description

Subcutaneous (SC) every week (QW) over the treatment period

Primary Outcome Measure Information:

Title

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

Description

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.

Time Frame

Baseline up to Week 104

Title

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

Description

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.

Time Frame

Baseline up to Week 26

Secondary Outcome Measure Information:

Title

Percentage of Participants Who Had Breakthrough Hemolysis Through Week 26 and 78

Description

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).

Time Frame

At Week 26 and 78

Title

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

Description

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

Time Frame

Baseline up to Week 26

Title

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

Description

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).

Time Frame

At Week 26 and 78

Title

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

Description

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.

Time Frame

Baseline up to Week 78

Title

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

Description

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.

Time Frame

Baseline, Week 26 and 78

Title

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

Description

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

Time Frame

Baseline, Week 26, 78, and 104

Title

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

Description

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

Time Frame

Baseline, Week 26, 78, and 104

Title

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

Description

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

Time Frame

Baseline, Week 26, 78, and 104

Title

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

Description

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

Time Frame

Baseline, Week 26, 78 and 104

Title

Serum Concentrations of Total REGN3918

Description

Serum Concentrations of total REGN3918 was reported.

Time Frame

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

Title

Number of Participants With Treatment-emergent Anti-Drug Antibodies (ADA) to REGN3918

Description

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).

Time Frame

Baseline up to Week 104

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trial Management

Organizational Affiliation

Regeneron Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Regeneron Study Site

City

Sha Tin

Country

Hong Kong

Facility Name

Regeneron Study Site

City

Budapest

ZIP/Postal Code

1907

Country

Hungary

Facility Name

Regeneron Study Site

City

Busan

ZIP/Postal Code

49241

Country

Korea, Republic of

Facility Name

Regeneron Study Site

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

Regeneron Study Site

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Facility Name

Regeneron Study Site

City

Seoul

ZIP/Postal Code

05030

Country

Korea, Republic of

Facility Name

Regeneron Study Site

City

Seoul

ZIP/Postal Code

06351

Country

Korea, Republic of

Facility Name

Regeneron Study Site

City

Seoul

ZIP/Postal Code

07985

Country

Korea, Republic of

Facility Name

Regeneron Study Site

City

Miri

State/Province

Sarawak

ZIP/Postal Code

98000

Country

Malaysia

Facility Name

Regeneron Study Site

City

Sibu

State/Province

Sarawak

ZIP/Postal Code

96000

Country

Malaysia

Facility Name

Regeneron Study Site

City

Kuala Terengganu

State/Province

Terengganu

ZIP/Postal Code

20400

Country

Malaysia

Facility Name

Regeneron Study Site

City

Taipei City

ZIP/Postal Code

10002

Country

Taiwan

Facility Name

Regeneron Study Site

City

Taoyuan City

ZIP/Postal Code

333

Country

Taiwan

Facility Name

Regeneron Study Site

City

Leeds

ZIP/Postal Code

LS97TF

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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 URL

https://vivli.org/

Paroxysmal Nocturnal Hemoglobinuria

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial