Pozelimab and Cemdisiran Combination Treatment in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy

Phase 2

Completed

• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Interventions: Drug: Pozelimab; Drug: Cemdisiran

• Registration Number: NCT04811716
• Lead Sponsor: Regeneron Pharmaceuticals

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-03-19
• Study First Submitted QC: 2021-03-19
• Study First Posted: 2021-03-23
• Study Start: 2021-07-29
• Primary Completion: 2022-10-25
• Study Completion: 2023-10-18
• Disposition First Submitted: 2023-10-24
• Disposition First Posted: 2023-10-26
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

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

Key

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pozelimab Q4W + Cemdisiran	Cemdisiran	-
Pozelimab Q2W + Cemdisiran	Pozelimab	-
Pozelimab Q2W + Cemdisiran	Cemdisiran	-
Pozelimab Q4W + Cemdisiran	Pozelimab	-

Primary Outcome Measures

Name	Time	Method
Incidence and severity of treatment emergent adverse events (TEAEs)	Through Week 28	Open Label Treatment Period (OLTP)

Secondary Outcome Measures

Name	Time	Method
Concentrations of cemdisiran in plasma	Up to Week 52	OLEP
Percent change of LDH from pre-treatment to end-of-treatment period	End of treatment period, approximately 28 Weeks	OLTP Pre-treatment (mean of LDH values prior to combination dosing); End-of-treatment (mean of LDH value at week 24- through week 28)
Maintenance of adequate control of hemolysis	Day 1 through Week 52	OLEP
Breakthrough hemolysis	Day 1 through Week 52	OLEP
Hemoglobin stabilization	Day 1 through Week 52	OLEP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels
Change in hemoglobin levels	Day 1 to Week 52	OLEP
Transfusion avoidance	Day 1 through Week 52	OLEP Not requiring a RBC transfusion as per protocol algorithm
Rate of RBCs transfused	Day 1 to Week 52	OLEP
Number of units of RBCs transfused	Day 1 to Week 52	OLEP
Adequate control of hemolysis	Day 1 through Week 52	OLEP
Change in CH50	Day 1 to Week 52	OLEP
AUC of LDH over time	Day 1 through Week 52	OLEP
Normalization of LDH	Day 1 through week 52
Area under the curve (AUC) of LDH over time	Day 1 through Week 28	OLTP
Change in GHS/QoL on the EORTC QLQ-C30	Day 1 to Week 52	OLEP
Change in PF scores on the EORTC QLQ-C30	Day 1 to Week 52	OLEP
Incidence and severity of TEAEs	Up to Week 52	OLEP
Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale	Day 1 to Week 52	OLEP
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)	Baseline to Week 28	OLTP EORTC QLQ-C30 comprises 30 items (i.e. single questions), 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. The remaining six single-item (dyspnoea, appetite loss, sleep disturbance, constipation, diarrhoea and the financial impact) scales assess symptoms. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).
Change in physical function (PF) scores on the EORTC QLQ-C30	Baseline to Week 28	OLTP
Concentrations of total pozelimab in serum	Up to Week 52	OLEP
Change from baseline in concentration of total C5	Baseline through Week 28	OLTP
Incidence of pozelimab anti-drug antibody (ADA) responses over time	Up to Week 52	OLEP
Incidence of cemdisiran anti-drug antibody (ADA) responses over time	Up to Week 52	OLEP
Incidence and severity of TEAEs for participants who received treatment intensification	Through Week 28	OLTP
Change of LDH	Day 1 to Week 52	OLEP
Percent change of LDH	Day 1 to Week 52	OLEP
Percent change in CH50	Day 1 to Week 52	OLEP
Concentrations of total C5	Up to Week 52	OLEP

Trial Locations

Locations (13)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Hospital Sibu; 🇲🇾 Sibu, Sarawak, Malaysia

Yonsei University College of Medicine, Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Pusan National University Hospital; 🇰🇷 Busan, Korea, Republic of

Prince of Wales Hospital; 🇭🇰 Hong Kong, New Territories, Hong Kong

Hospital Sultanah Nur Zahirah; 🇲🇾 Kuala Terengganu, Terengganu, Malaysia

Ewha Womans University Medical Centre; 🇰🇷 Seoul, Korea, Republic of

Hospital Miri; 🇲🇾 Miri, Sarawak, Malaysia

Chang Gung Memorial Hospital; 🇨🇳 Taoyuan City, Taiwan

D l Pesti Centrumk rh z Orsz gos Hematol giai s Infektol giai Int zet; 🇭🇺 Budapest, Nagyvárad Tér 1, Hungary

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

St. James's University Hospital; 🇬🇧 Leeds, West Yorkshire, United Kingdom

Samsung Medical Center; 🇰🇷 Seoul, Seoul Teugbyeolsi, Korea, Republic of