Clinical trial NCT04811716: Pozelimab and Cemdisiran Combination Treatment in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: PNH
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-03-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Key Inclusion Criteria:

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

Key Exclusion Criteria:

1. 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
2. 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
3. Significant protocol deviation(s) in the parent study based on the investigator's judgment as described in the protocol
4. 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
5. Known hypersensitivity to cemdisiran or any component of cemdisiran formulation

NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply

Primary outcomes:
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Through Week 28
Secondary outcomes:
measure: Percent Change of Lactate Dehydrogenase (LDH) From Pre-treatment to End-of-treatment Period
timeFrame: End of treatment period, approximately 28 Weeks
measure: Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) through Week 28
measure: Percentage of Participants Maintaining Adequate Control of Hemolysis From Week 4 Through Week 28
timeFrame: Week 4 through Week 28
measure: Percentage of Participants With Adequate Control of Hemolysis at Each Visit Day 1 Through Week 28
timeFrame: Day 1 through Week 28
measure: Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) through Week 28
measure: Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) through Week 28
measure: Average LDH (U/L) Based on Area Under the Curve (AUC) From OLTP Week 4 Through Week 28
timeFrame: Week 4 through Week 28
measure: Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) through Week 28
measure: Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) through Week 28
measure: Change in Hemoglobin Levels From Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) to Week 28
measure: Percentage of Participants With Transfusion Avoidance From Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) to Week 28
measure: Rate of Red Blood Cells (RBCs) Transfused From Baseline (Day 1) to Week 28
timeFrame: Baseline (Day 1) to Week 28
measure: Number of Per-Protocol RBC Units Transfused From Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) to Week 28
measure: Change in Total Complement Hemolysis Activity Assay (CH50) From Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) to Week 28
measure: Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) to Week 28
measure: 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
timeFrame: Baseline (Day 1) to Week 28
measure: Change in Physical Function (PF) Scores on the EORTC QLQ-C30 From Baseline (Day 1) Through Week 28
timeFrame: Baseline (Day 1) to Week 28
measure: Concentrations of Total Pozelimab in Serum on Week 28
timeFrame: On Week 28
measure: Concentrations of Cemdisiran in Plasma on Week 28
timeFrame: On Week 28
measure: Concentrations of Total C5 on Week 28
timeFrame: On Week 28
measure: Number of Participants With Pozelimab Anti-Drug Antibody (ADA) Responses Over Time
timeFrame: Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52])
measure: Number of Participants With Cemdisiran Anti-Drug Antibody (ADA) Responses Over Time
timeFrame: Up to Week 52 (OLTP [ Week 0 - Week 28] + OLEP [Week 28 - Week 52])
measure: Percentage of Participants With TEAEs for Participants Who Received Treatment Intensification
timeFrame: Through Week 28
measure: Change of LDH From Baseline (Day 1e) to Week 24e
timeFrame: Baseline (Day 1e) to Week 24e
measure: Percent Change of LDH From OLEP Baseline (Day 1e) to Week 24e
timeFrame: Baseline (Day 1e) to Week 24e
measure: Change of LDH From Baseline (Day 1e) to Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Percent Change of LDH From Baseline (Day 1e) to Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 24e
timeFrame: Baseline (Day 1e) through Week 24e
measure: Percentage of Participants Maintaining Adequate Control of Hemolysis From Baseline (Day 1e) Through Week 52e
timeFrame: Baseline (Day 1e) through Week 52e
measure: Percentage of Participants With Adequate Control of Hemolysis at Each Visit From Baseline (Day 1e) Through Week 52e
timeFrame: Baseline (Day 1e) through Week 52e
measure: Percentage of Participants With Normalization of LDH at Each Visit From Baseline (Day 1e) Through Week 52e
timeFrame: Baseline (Day 1e) through week 52e
measure: Average LDH (U/L) Based on Area Under the Curve (AUC) From OLEP Baseline (Day 1e) Through Week 52e
timeFrame: Baseline (Day 1e) through Week 52e
measure: Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 24e
timeFrame: Baseline (Day 1e) through Week 24e
measure: Percentage of Participants With Breakthrough Hemolysis From Baseline (Day 1e) Through Week 52e
timeFrame: Baseline (Day 1e) through Week 52e
measure: Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 24e
timeFrame: Baseline (Day 1e) through Week 24e
measure: Percentage of Participants With Hemoglobin Stabilization From Baseline (Day 1e) Through Week 52e
timeFrame: Baseline (Day 1e) through Week 52e
measure: Change in Hemoglobin Levels From Baseline (Day 1e) to Week 24e
timeFrame: Baseline (Day 1e) to Week 24e
measure: Change in Hemoglobin Levels From Baseline (Day 1e) to Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 24e
timeFrame: Baseline (Day 1e) through Week 24e
measure: Percentage of Participants With Per-Protocol Transfusion Avoidance From Baseline (Day 1e) Through Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Rate of RBCs Transfused From Baseline (Day 1e) to Week 24e
timeFrame: Baseline (Day 1e) to Week 24e
measure: Rate of RBCs Transfused From Baseline (Day 1e) to Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 24e
timeFrame: Baseline (Day 1e) to Week 24e
measure: Number of Units of RBCs Transfused From Baseline (Day 1e) to Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Change in CH50 From Baseline (Day 1e) to Week 16e
timeFrame: Baseline (Day 1e) to Week 16e
measure: Change in CH50 From Baseline (Day 1e) to Week 24e
timeFrame: Baseline (Day 1e) to Week 24e
measure: Change in CH50 From Baseline (Day 1e) to Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Percent Change in CH50 From Baseline (Day 1e) to Week 16e
timeFrame: Baseline (Day 1e) to Week 16e
measure: Percent Change in CH50 From Baseline (Day 1e) to Week 24e
timeFrame: Baseline (Day 1e) to Week 24e
measure: Percent Change in CH50 From Baseline (Day 1e) to Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Change in Fatigue as Measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale From Baseline (Day 1e) to Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Change in GHS/QoL on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Change in PF Scores on the EORTC QLQ-C30 From Baseline (Day 1e) to Week 52e
timeFrame: Baseline (Day 1e) to Week 52e
measure: Percentage of Participants With TEAEs Up to Week 52
timeFrame: Up to Week 52
measure: Concentrations of Total Pozelimab in Serum on Week 52
timeFrame: On Week 52
measure: Concentrations of Total C5 on Week 52
timeFrame: On Week 52
measure: Concentrations of Cemdisiran in Plasma on Week 52
timeFrame: On Week 52
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
state: New Territories
city: Budapest
country: Hungary
facility: D l Pesti Centrumk rh z Orsz gos Hematol giai s Infektol giai Int zet
state: Nagyvárad Tér 1
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University College of Medicine, Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Medical Centre
city: Miri
country: Malaysia
facility: Hospital Miri
state: Sarawak
city: Sibu
country: Malaysia
facility: Hospital Sibu
state: Sarawak
city: Kuala Terengganu
country: Malaysia
facility: Hospital Sultanah Nur Zahirah
state: Terengganu
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Leeds
country: United Kingdom
facility: St. James's University Hospital
state: West Yorkshire
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: