Back to resultsPozelimab and Cemdisiran Combination Treatment in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy
Primary Purpose
Paroxysmal Nocturnal Hemoglobinuria
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Pozelimab
Cemdisiran
Sponsored by
About this trial
This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria focused on measuring PNH
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:
- 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
Sites / Locations
- Prince of Wales Hospital
- D l Pesti Centrumk rh z Orsz gos Hematol giai s Infektol giai Int zet
- Samsung Medical Center
- Pusan National University Hospital
- Seoul National University Hospital
- Yonsei University College of Medicine, Severance Hospital
- Ewha Womans University Medical Centre
- Hospital Miri
- Hospital Sibu
- Hospital Sultanah Nur Zahirah
- National Taiwan University Hospital
- Chang Gung Memorial Hospital
- St. James's University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Pozelimab Q4W + Cemdisiran
Pozelimab Q2W + Cemdisiran
Arm Description
Outcomes
Primary Outcome Measures
Incidence and severity of treatment emergent adverse events (TEAEs)
Open Label Treatment Period (OLTP)
Secondary Outcome Measures
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)
Maintenance of adequate control of hemolysis
OLTP
Maintenance of adequate control of hemolysis
OLTP
Adequate control of hemolysis
OLTP
Normalization of LDH
OLTP
Area under the curve (AUC) of LDH over time
OLTP
AUC of LDH over time
OLTP
Breakthrough hemolysis
OLTP
Hemoglobin stabilization
OLTP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels
Change in hemoglobin levels
OLTP
Transfusion avoidance
OLTP Not requiring a RBC transfusion as per protocol algorithm
Rate of RBCs transfused
OLTP
Number of units of RBCs transfused
OLTP
Change in CH50
OLTP
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
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).
Change in physical function (PF) scores on the EORTC QLQ-C30
OLTP
Concentrations of total pozelimab in serum
OLTP
Concentrations of cemdisiran in plasma
OLTP
Change from baseline in concentration of total C5
OLTP
Incidence of pozelimab anti-drug antibody (ADA) responses over time
OLTP
Incidence of cemdisiran anti-drug antibody (ADA) responses over time
OLTP
Incidence and severity of TEAEs for participants who received treatment intensification
OLTP
Change of LDH
Optional Open-Label Extension Period (OLEP)
Percent change of LDH
OLEP
Change of LDH
OLEP
Percent change of LDH
OLEP
Maintenance of adequate control of hemolysis
OLEP
Maintenance of adequate control of hemolysis
OLEP
Adequate control of hemolysis
OLEP
Normalization of LDH
AUC of LDH over time
OLEP
Breakthrough hemolysis
OLEP
Breakthrough hemolysis
OLEP
Hemoglobin stabilization
OLEP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels
Hemoglobin stabilization
OLEP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels
Change in hemoglobin levels
OLEP
Change in hemoglobin levels
OLEP
Transfusion avoidance
OLEP Not requiring a RBC transfusion as per protocol algorithm
Transfusion avoidance
OLEP Not requiring a RBC transfusion as per protocol algorithm
Rate of RBCs transfused
OLEP
Rate of RBCs transfused
OLEP
Number of units of RBCs transfused
OLEP
Number of units of RBCs transfused
OLEP
Change in CH50
OLEP
Change in CH50
OLEP
Change in CH50
OLEP
Percent change in CH50
OLEP
Percent change in CH50
OLEP
Percent change in CH50
OLEP
Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale
OLEP
Change in GHS/QoL on the EORTC QLQ-C30
OLEP
Change in PF scores on the EORTC QLQ-C30
OLEP
Incidence and severity of TEAEs
OLEP
Concentrations of total pozelimab in serum
OLEP
Concentrations of total C5
OLEP
Concentrations of cemdisiran in plasma
OLEP
Incidence of pozelimab anti-drug antibody (ADA) responses over time
OLEP
Incidence of cemdisiran anti-drug antibody (ADA) responses over time
OLEP
Full Information
NCT ID
NCT04811716
First Posted
March 19, 2021
Last Updated
April 18, 2023
Sponsor
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04811716
Brief Title
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
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 28, 2021 (Actual)
Primary Completion Date
October 25, 2022 (Actual)
Study Completion Date
October 24, 2024 (Anticipated)
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
Data Monitoring Committee
No
5. Study Description
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
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 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pozelimab Q4W + Cemdisiran
Arm Type
Experimental
Arm Title
Pozelimab Q2W + Cemdisiran
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Pozelimab
Other Intervention Name(s)
REGN3918
Intervention Description
Administered Sub-cutaneous (SC) per protocol
Intervention Type
Drug
Intervention Name(s)
Cemdisiran
Other Intervention Name(s)
ALN-CC5
Intervention Description
Administered SC per protocol
Primary Outcome Measure Information:
Title
Incidence and severity of treatment emergent adverse events (TEAEs)
Description
Open Label Treatment Period (OLTP)
Time Frame
Through Week 28
Secondary Outcome Measure Information:
Title
Percent change of LDH from pre-treatment to end-of-treatment period
Description
OLTP Pre-treatment (mean of LDH values prior to combination dosing); End-of-treatment (mean of LDH value at week 24- through week 28)
Time Frame
End of treatment period, approximately 28 Weeks
Title
Maintenance of adequate control of hemolysis
Description
OLTP
Time Frame
Day 1 through Week 28
Title
Maintenance of adequate control of hemolysis
Description
OLTP
Time Frame
Week 4 through Week 28
Title
Adequate control of hemolysis
Description
OLTP
Time Frame
Day 1 through Week 28
Title
Normalization of LDH
Description
OLTP
Time Frame
Day 1 through Week 28
Title
Area under the curve (AUC) of LDH over time
Description
OLTP
Time Frame
Day 1 through Week 28
Title
AUC of LDH over time
Description
OLTP
Time Frame
Week 4 through Week 28
Title
Breakthrough hemolysis
Description
OLTP
Time Frame
Baseline through Week 28
Title
Hemoglobin stabilization
Description
OLTP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels
Time Frame
Baseline through Week 28
Title
Change in hemoglobin levels
Description
OLTP
Time Frame
Baseline to Week 28
Title
Transfusion avoidance
Description
OLTP Not requiring a RBC transfusion as per protocol algorithm
Time Frame
Baseline to Week 28
Title
Rate of RBCs transfused
Description
OLTP
Time Frame
Baseline to Week 28
Title
Number of units of RBCs transfused
Description
OLTP
Time Frame
Baseline to Week 28
Title
Change in CH50
Description
OLTP
Time Frame
Baseline to Week 28
Title
Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale
Description
OLTP FACIT fatigue is a 13 item scale and for each item 4 is not at all fatigued to 0 very much fatigued
Time Frame
Baseline to Week 28
Title
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)
Description
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).
Time Frame
Baseline to Week 28
Title
Change in physical function (PF) scores on the EORTC QLQ-C30
Description
OLTP
Time Frame
Baseline to Week 28
Title
Concentrations of total pozelimab in serum
Description
OLTP
Time Frame
Up to Week 28
Title
Concentrations of cemdisiran in plasma
Description
OLTP
Time Frame
Up to Week 28
Title
Change from baseline in concentration of total C5
Description
OLTP
Time Frame
Baseline through Week 28
Title
Incidence of pozelimab anti-drug antibody (ADA) responses over time
Description
OLTP
Time Frame
Up to Week 28
Title
Incidence of cemdisiran anti-drug antibody (ADA) responses over time
Description
OLTP
Time Frame
Up to Week 28
Title
Incidence and severity of TEAEs for participants who received treatment intensification
Description
OLTP
Time Frame
Through Week 28
Title
Change of LDH
Description
Optional Open-Label Extension Period (OLEP)
Time Frame
Day 1 to Week 24
Title
Percent change of LDH
Description
OLEP
Time Frame
Day 1 to Week 24
Title
Change of LDH
Description
OLEP
Time Frame
Day 1 to Week 52
Title
Percent change of LDH
Description
OLEP
Time Frame
Day 1 to Week 52
Title
Maintenance of adequate control of hemolysis
Description
OLEP
Time Frame
Day 1 through Week 24
Title
Maintenance of adequate control of hemolysis
Description
OLEP
Time Frame
Day 1 through Week 52
Title
Adequate control of hemolysis
Description
OLEP
Time Frame
Day 1 through Week 52
Title
Normalization of LDH
Time Frame
Day 1 through week 52
Title
AUC of LDH over time
Description
OLEP
Time Frame
Day 1 through Week 52
Title
Breakthrough hemolysis
Description
OLEP
Time Frame
Day 1 through Week 24
Title
Breakthrough hemolysis
Description
OLEP
Time Frame
Day 1 through Week 52
Title
Hemoglobin stabilization
Description
OLEP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels
Time Frame
Day 1 through Week 24
Title
Hemoglobin stabilization
Description
OLEP Participants who do not receive RBC transfusion and have no decrease in hemoglobin levels
Time Frame
Day 1 through Week 52
Title
Change in hemoglobin levels
Description
OLEP
Time Frame
Day 1 to Week 24
Title
Change in hemoglobin levels
Description
OLEP
Time Frame
Day 1 to Week 52
Title
Transfusion avoidance
Description
OLEP Not requiring a RBC transfusion as per protocol algorithm
Time Frame
Day 1 through Week 24
Title
Transfusion avoidance
Description
OLEP Not requiring a RBC transfusion as per protocol algorithm
Time Frame
Day 1 through Week 52
Title
Rate of RBCs transfused
Description
OLEP
Time Frame
Day 1 to Week 24
Title
Rate of RBCs transfused
Description
OLEP
Time Frame
Day 1 to Week 52
Title
Number of units of RBCs transfused
Description
OLEP
Time Frame
Day 1 to Week 24
Title
Number of units of RBCs transfused
Description
OLEP
Time Frame
Day 1 to Week 52
Title
Change in CH50
Description
OLEP
Time Frame
Day 1 to Week 16
Title
Change in CH50
Description
OLEP
Time Frame
Day 1 to Week 24
Title
Change in CH50
Description
OLEP
Time Frame
Day 1 to Week 52
Title
Percent change in CH50
Description
OLEP
Time Frame
Day 1 to Week 16
Title
Percent change in CH50
Description
OLEP
Time Frame
Day 1 to Week 24
Title
Percent change in CH50
Description
OLEP
Time Frame
Day 1 to Week 52
Title
Change in fatigue as measured by Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale
Description
OLEP
Time Frame
Day 1 to Week 52
Title
Change in GHS/QoL on the EORTC QLQ-C30
Description
OLEP
Time Frame
Day 1 to Week 52
Title
Change in PF scores on the EORTC QLQ-C30
Description
OLEP
Time Frame
Day 1 to Week 52
Title
Incidence and severity of TEAEs
Description
OLEP
Time Frame
Up to Week 52
Title
Concentrations of total pozelimab in serum
Description
OLEP
Time Frame
Up to Week 52
Title
Concentrations of total C5
Description
OLEP
Time Frame
Up to Week 52
Title
Concentrations of cemdisiran in plasma
Description
OLEP
Time Frame
Up to Week 52
Title
Incidence of pozelimab anti-drug antibody (ADA) responses over time
Description
OLEP
Time Frame
Up to Week 52
Title
Incidence of cemdisiran anti-drug antibody (ADA) responses over time
Description
OLEP
Time Frame
Up to Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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:
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
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
Prince of Wales Hospital
City
Hong Kong
State/Province
New Territories
ZIP/Postal Code
550540
Country
Hong Kong
Facility Name
D l Pesti Centrumk rh z Orsz gos Hematol giai s Infektol giai Int zet
City
Budapest
State/Province
Nagyvárad Tér 1
ZIP/Postal Code
1907
Country
Hungary
Facility Name
Samsung Medical Center
City
Seoul
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Pusan National University Hospital
City
Busan
ZIP/Postal Code
49241
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Yonsei University College of Medicine, Severance Hospital
City
Seoul
ZIP/Postal Code
3722
Country
Korea, Republic of
Facility Name
Ewha Womans University Medical Centre
City
Seoul
ZIP/Postal Code
7985
Country
Korea, Republic of
Facility Name
Hospital Miri
City
Miri
State/Province
Sarawak
ZIP/Postal Code
98000
Country
Malaysia
Facility Name
Hospital Sibu
City
Sibu
State/Province
Sarawak
ZIP/Postal Code
96000
Country
Malaysia
Facility Name
Hospital Sultanah Nur Zahirah
City
Kuala Terengganu
State/Province
Terengganu
ZIP/Postal Code
20400
Country
Malaysia
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Chang Gung Memorial Hospital
City
Taoyuan City
ZIP/Postal Code
333
Country
Taiwan
Facility Name
St. James's University Hospital
City
Leeds
State/Province
West Yorkshire
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
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 made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
IPD Sharing Access Criteria
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
IPD Sharing URL
https://vivli.org/
Learn more about this trial
Pozelimab and Cemdisiran Combination Treatment in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Who Have Received Pozelimab Monotherapy
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