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

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04811716
• Other study ID #: R3918-PNH-2092
• Secondary ID: 2020-005005-17
• Status: Completed
• Phase: Phase 2
• Start date: July 29, 2021
• Est. completion date: October 18, 2023

Study information

• Verified date: November 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: October 18, 2023
• Est. primary completion date: October 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Intervention

Drug:
• Pozelimab
Administered Sub-cutaneous (SC) per protocol
• Cemdisiran
Administered SC per protocol

Locations

Country	Name	City	State
Hong Kong	Prince of Wales Hospital	Hong Kong	New Territories
Hungary	D l Pesti Centrumk rh z Orsz gos Hematol giai s Infektol giai Int zet	Budapest	Nagyvárad Tér 1
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Ewha Womans University Medical Centre	Seoul
Korea, Republic of	Samsung Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University College of Medicine, Severance Hospital	Seoul
Malaysia	Hospital Sultanah Nur Zahirah	Kuala Terengganu	Terengganu
Malaysia	Hospital Miri	Miri	Sarawak
Malaysia	Hospital Sibu	Sibu	Sarawak
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital	Taoyuan City
United Kingdom	St. James's University Hospital	Leeds	West Yorkshire

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

Hong Kong,  Hungary,  Korea, Republic of,  Malaysia,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of treatment emergent adverse events (TEAEs)	Open Label Treatment Period (OLTP)	Through Week 28
Secondary	Percent change of LDH from pre-treatment to end-of-treatment period	OLTP Pre-treatment (mean of LDH values prior to combination dosing); End-of-treatment (mean of LDH value at week 24- through week 28)	End of treatment period, approximately 28 Weeks
Secondary	Maintenance of adequate control of hemolysis	OLTP	Day 1 through Week 28
Secondary	Maintenance of adequate control of hemolysis	OLTP	Week 4 through Week 28
Secondary	Adequate control of hemolysis	OLTP	Day 1 through Week 28
Secondary	Normalization of LDH	OLTP	Day 1 through Week 28
Secondary	Area under the curve (AUC) of LDH over time	OLTP	Day 1 through Week 28
Secondary	AUC of LDH over time	OLTP	Week 4 through Week 28
Secondary	Breakthrough hemolysis	OLTP	Baseline through Week 28
Secondary	Hemoglobin stabilization	OLTP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels	Baseline through Week 28
Secondary	Change in hemoglobin levels	OLTP	Baseline to Week 28
Secondary	Transfusion avoidance	OLTP Not requiring a RBC transfusion as per protocol algorithm	Baseline to Week 28
Secondary	Rate of RBCs transfused	OLTP	Baseline to Week 28
Secondary	Number of units of RBCs transfused	OLTP	Baseline to Week 28
Secondary	Change in CH50	OLTP	Baseline to Week 28
Secondary	Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale	OLTP FACIT fatigue is a 13 item scale and for each item 4 is not at all fatigued to 0 very much fatigued	Baseline to Week 28
Secondary	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)	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).	Baseline to Week 28
Secondary	Change in physical function (PF) scores on the EORTC QLQ-C30	OLTP	Baseline to Week 28
Secondary	Concentrations of total pozelimab in serum	OLTP	Up to Week 28
Secondary	Concentrations of cemdisiran in plasma	OLTP	Up to Week 28
Secondary	Change from baseline in concentration of total C5	OLTP	Baseline through Week 28
Secondary	Incidence of pozelimab anti-drug antibody (ADA) responses over time	OLTP	Up to Week 28
Secondary	Incidence of cemdisiran anti-drug antibody (ADA) responses over time	OLTP	Up to Week 28
Secondary	Incidence and severity of TEAEs for participants who received treatment intensification	OLTP	Through Week 28
Secondary	Change of LDH	Optional Open-Label Extension Period (OLEP)	Day 1 to Week 24
Secondary	Percent change of LDH	OLEP	Day 1 to Week 24
Secondary	Change of LDH	OLEP	Day 1 to Week 52
Secondary	Percent change of LDH	OLEP	Day 1 to Week 52
Secondary	Maintenance of adequate control of hemolysis	OLEP	Day 1 through Week 24
Secondary	Maintenance of adequate control of hemolysis	OLEP	Day 1 through Week 52
Secondary	Adequate control of hemolysis	OLEP	Day 1 through Week 52
Secondary	Normalization of LDH		Day 1 through week 52
Secondary	AUC of LDH over time	OLEP	Day 1 through Week 52
Secondary	Breakthrough hemolysis	OLEP	Day 1 through Week 24
Secondary	Breakthrough hemolysis	OLEP	Day 1 through Week 52
Secondary	Hemoglobin stabilization	OLEP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels	Day 1 through Week 24
Secondary	Hemoglobin stabilization	OLEP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels	Day 1 through Week 52
Secondary	Change in hemoglobin levels	OLEP	Day 1 to Week 24
Secondary	Change in hemoglobin levels	OLEP	Day 1 to Week 52
Secondary	Transfusion avoidance	OLEP Not requiring a RBC transfusion as per protocol algorithm	Day 1 through Week 24
Secondary	Transfusion avoidance	OLEP Not requiring a RBC transfusion as per protocol algorithm	Day 1 through Week 52
Secondary	Rate of RBCs transfused	OLEP	Day 1 to Week 24
Secondary	Rate of RBCs transfused	OLEP	Day 1 to Week 52
Secondary	Number of units of RBCs transfused	OLEP	Day 1 to Week 24
Secondary	Number of units of RBCs transfused	OLEP	Day 1 to Week 52
Secondary	Change in CH50	OLEP	Day 1 to Week 16
Secondary	Change in CH50	OLEP	Day 1 to Week 24
Secondary	Change in CH50	OLEP	Day 1 to Week 52
Secondary	Percent change in CH50	OLEP	Day 1 to Week 16
Secondary	Percent change in CH50	OLEP	Day 1 to Week 24
Secondary	Percent change in CH50	OLEP	Day 1 to Week 52
Secondary	Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale	OLEP	Day 1 to Week 52
Secondary	Change in GHS/QoL on the EORTC QLQ-C30	OLEP	Day 1 to Week 52
Secondary	Change in PF scores on the EORTC QLQ-C30	OLEP	Day 1 to Week 52
Secondary	Incidence and severity of TEAEs	OLEP	Up to Week 52
Secondary	Concentrations of total pozelimab in serum	OLEP	Up to Week 52
Secondary	Concentrations of total C5	OLEP	Up to Week 52
Secondary	Concentrations of cemdisiran in plasma	OLEP	Up to Week 52
Secondary	Incidence of pozelimab anti-drug antibody (ADA) responses over time	OLEP	Up to Week 52
Secondary	Incidence of cemdisiran anti-drug antibody (ADA) responses over time	OLEP	Up to Week 52