A Randomized, Open-label, Two-arm Study to Evaluate the Safety, Efficacy, and Pharmacodynamic Effects of Pozelimab and Cemdisiran Combination Treatment in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy

Regeneron Pharmaceuticals13 sites in 6 countries24 target enrollmentJuly 29, 2021

ConditionsParoxysmal Nocturnal Hemoglobinuria

InterventionsPozelimab Cemdisiran

DrugsPozelimab Cemdisiran

Overview

Phase: Phase 2
Intervention: Pozelimab
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Sponsor: Regeneron Pharmaceuticals
Enrollment: 24
Locations: 13
Primary Endpoint: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objective of the study is to evaluate the safety and tolerability of 2 dosing regimens of pozelimab and cemdisiran combination therapy during the open-label treatment period (OLTP)

The secondary objectives of the study are:

To evaluate the effect of the combination treatment on the following parameters of intravascular hemolysis: lactate dehydrogenase (LDH) control, breakthrough hemolysis, and inhibition of total complement hemolysis activity (CH50)
To evaluate the effect of the combination treatment on hemoglobin levels
To evaluate the effect of the combination treatment on red blood cell (RBC) transfusion requirements
To evaluate the effect of the combination treatment on clinical outcome assessments (COAs) measuring fatigue and health related quality of life
To assess the concentrations of total pozelimab in serum and total complement component (C) 5 and cemdisiran in plasma
To assess immunogenicity to pozelimab and cemdisiran
To evaluate the long-term safety and efficacy of pozelimab and cemdisiran in an optional open-label extension period (OLEP)
To assess safety after treatment intensification with pozelimab and cemdisiran

Registry

clinicaltrials.gov

Start Date

July 29, 2021

End Date

October 18, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Regeneron Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participants with PNH who are receiving treatment with pozelimab monotherapy in the R3918- PNH-1868 study (NCT04162470)

Exclusion Criteria

•Documented, positive polymerase chain reaction (PCR) or equivalent test based on regional recommendations for COVID-19 or suspected SARS-CoV-2 infection as defined in the protocol
•Participants with documented history of liver cirrhosis or participants with liver disease with evidence of currently impaired liver function; or participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) as described in the protocol
•Significant protocol deviation(s) in the parent study based on the investigator's judgment as described in the protocol
•Any new condition or worsening of an existing condition which, in the opinion of the investigator, would make the participant unsuitable for enrollment or would jeopardize the safety of the participant
•Known hypersensitivity to cemdisiran or any component of cemdisiran formulation
•NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Arms & Interventions

Pozelimab Q4W + Cemdisiran

Intervention: Pozelimab

Pozelimab Q4W + Cemdisiran

Intervention: Cemdisiran

Pozelimab Q2W + Cemdisiran

Intervention: Pozelimab

Pozelimab Q2W + Cemdisiran

Intervention: Cemdisiran

Outcomes

Primary Outcomes

Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)

Time Frame: Through Week 28

Open Label Treatment Period (OLTP)

Secondary Outcomes

Concentrations of Cemdisiran in Plasma on Week 28(On Week 28)
Concentrations of Total C5 on Week 28(On Week 28)
Concentrations of Total Pozelimab in Serum on Week 52(On Week 52)
Change of LDH From Baseline (Day 1e) to Week 24e(Baseline (Day 1e) to Week 24e)
Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28(Day 1 through Week 28)
Percent Change of Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period(End of treatment period, approximately 28 Weeks)
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28(Baseline (Day 1) through Week 28)
Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28(Week 4 through Week 28)
Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28(Baseline (Day 1) through Week 28)
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Baseline (Day 1) Through Week 28(Baseline (Day 1) through Week 28)
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Week 4 Through Week 28(Week 4 through Week 28)
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1) Through Week 28(Baseline (Day 1) through Week 28)
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1) Through Week 28(Baseline (Day 1) through Week 28)
Change in Hemoglobin Levels From Baseline (Day 1) Through Week 28(Baseline (Day 1) to Week 28)
Percentage of Participants With Transfusion Avoidance From Baseline (Day 1) Through Week 28(Baseline (Day 1) to Week 28)
Rate of Red Blood Cells (RBCs) Transfused From Baseline (Day 1) to Week 28(Baseline (Day 1) to Week 28)
Number of Per-Protocol RBC Units Transfused From Baseline (Day 1) Through Week 28(Baseline (Day 1) to Week 28)
Change in Total Complement Hemolysis Activity Assay (CH50) From Baseline (Day 1) Through Week 28(Baseline (Day 1) to Week 28)
Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1) Through Week 28(Baseline (Day 1) to Week 28)
Change in Global Health Status/Quality of Life Scale (GHS/QoL) on the European Organization for Research and Treatment of Cancer: Quality-of-Life Questionnaire Core 30 Items (EORTC QLQ-C30) From Baseline (Day 1) Through Week 28(Baseline (Day 1) to Week 28)
Change in Physical Function (PF) Scores on the EORTC QLQ-C30 From Baseline (Day 1) Through Week 28(Baseline (Day 1) to Week 28)
Concentrations of Total Pozelimab in Serum on Week 28(On Week 28)
Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time(Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52]))
Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time(Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52]))
Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification(Through Week 28)
Percent Change of LDH From OLEP Baseline (Day 1e) to Week 24e(Baseline (Day 1e) to Week 24e)
Change of LDH From Baseline (Day 1e) to Week 52e(Baseline (Day 1e) to Week 52e)
Percent Change of LDH From Baseline (Day 1e) to Week 52e(Baseline (Day 1e) to Week 52e)
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 24e(Baseline (Day 1e) through Week 24e)
Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 52e(Baseline (Day 1e) through Week 52e)
Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e(Baseline (Day 1e) through Week 52e)
Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e(Baseline (Day 1e) through week 52e)
Average LDH (U/L) Based on Area Under the Curve (AUC) From OLEP Baseline (Day 1e) Through Week 52e(Baseline (Day 1e) through Week 52e)
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 24e(Baseline (Day 1e) through Week 24e)
Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 52e(Baseline (Day 1e) through Week 52e)
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 24e(Baseline (Day 1e) through Week 24e)
Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 52e(Baseline (Day 1e) through Week 52e)
Change in Hemoglobin Levels From Baseline (Day 1e) to Week 24e(Baseline (Day 1e) to Week 24e)
Change in Hemoglobin Levels From Baseline (Day 1e) to Week 52e(Baseline (Day 1e) to Week 52e)
Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 24e(Baseline (Day 1e) through Week 24e)
Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 52e(Baseline (Day 1e) to Week 52e)
Rate of RBCs Transfused From Baseline (Day 1e) to Week 24e(Baseline (Day 1e) to Week 24e)
Rate of RBCs Transfused From Baseline (Day 1e) to Week 52e(Baseline (Day 1e) to Week 52e)
Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 24e(Baseline (Day 1e) to Week 24e)
Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 52e(Baseline (Day 1e) to Week 52e)
Change in CH50 From Baseline (Day 1e) to Week 16e(Baseline (Day 1e) to Week 16e)
Change in CH50 From Baseline (Day 1e) to Week 24e(Baseline (Day 1e) to Week 24e)
Change in CH50 From Baseline (Day 1e) to Week 52e(Baseline (Day 1e) to Week 52e)
Percent Change in CH50 From Baseline (Day 1e) to Week 16e(Baseline (Day 1e) to Week 16e)
Percent Change in CH50 From Baseline (Day 1e) to Week 24e(Baseline (Day 1e) to Week 24e)
Percent Change in CH50 From Baseline (Day 1e) to Week 52e(Baseline (Day 1e) to Week 52e)
Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1e) to Week 52e(Baseline (Day 1e) to Week 52e)
Change in GHS/QoL on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e(Baseline (Day 1e) to Week 52e)
Change in PF Scores on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e(Baseline (Day 1e) to Week 52e)
Percentage of Participants With TEAEs Up to Week 52(Up to Week 52)
Concentrations of Total C5 on Week 52(On Week 52)
Concentrations of Cemdisiran in Plasma on Week 52(On Week 52)