Back to resultsEfficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (ACCESS 2)
Primary Purpose
Paroxysmal Nocturnal Hemoglobinuria
Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Cemdisiran
Eculizumab
Pozelimab
Ravulizumab
Sponsored by
About this trial
This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria focused on measuring PNH
Eligibility Criteria
Key Inclusion Criteria:
- Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
- Treated with eculizumab or ravulizumab prior to screening visit as described in the protocol Note: Biosimilars are not permitted, unless approved by the Sponsor
Key Exclusion Criteria:
- Patients with a screening LDH >1.5 × ULN who have not taken their C5 inhibitor within the labeled dose interval at the dose prior to the screening LDH assessment
- Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
- Body weight < 40 kilograms at screening visit
- Any use of complement inhibitor therapy other than eculizumab or ravulizumab in the 26 weeks prior to the screening visit or planned use during the study with the exception of study treatments
- Not meeting meningococcal vaccination requirements for eculizumab or ravulizumab according to the current local prescribing information (where available) and at a minimum documentation of meningococcal vaccination within 5 years prior to screening visit.
- Any contraindication for receiving Neisseria meningitidis vaccination.
- Positive for hepatitis B, and/ or hepatitis C as described in the protocol
- History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
- Participation in another interventional clinical study (except R3918-PNH-2021) or use of any experimental therapy within 30 days before screening visit or within 5 half-lives of that investigational product, whichever is greater, with the exception of eculizumab or ravulizumab.
- Patients with functional or anatomic asplenia
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Sites / Locations
- Regeneron Research Facility
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Pozelimab and Cemdisiran
Anti-C5 standard-of-care
Arm Description
Randomized 1:1
Randomized 1:1
Outcomes
Primary Outcome Measures
Percent change in lactate dehydrogenase (LDH)
Secondary Outcome Measures
Proportion of patients with transfusion avoidance
Patients who do not receive an RBC transfusion as per protocol algorithm based on post baseline hemoglobin values
Proportion of patients with transfusion avoidance
Patients who do not receive an RBC transfusion as per protocol algorithm based on post baseline hemoglobin values
Proportion of patients with breakthrough hemolysis
Patients with an increase in LDH with concomitant signs or symptoms associated with hemolysis as described in the protocol
Proportion of patients with breakthrough hemolysis
Patients with an increase in LDH with concomitant signs or symptoms associated with hemolysis as described in the protocol
Proportion of patients with hemoglobin stabilization
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level as defined in the protocol
Proportion of patients with hemoglobin stabilization
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level as defined in the protocol
Proportion of patients with adequate control of LDH
Proportion of patients with adequate control of LDH as defined in the protocol
Proportion of patients with adequate control of LDH
Proportion of patients with adequate control of LDH as defined in the protocol
Proportion of patients with normalization of LDH
Proportion of patients with normalization of LDH as defined in the protocol
Proportion of patients with normalization of LDH
Proportion of patients with normalization of LDH as defined in the protocol
Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale
The FACIT-Fatigue is a 13 item, self-administered clinical outcome assessment (COA) assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health related quality of life (QoL) in patients with cancer and other chronic illnesses. The FACIT-Fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.
Change in Physical Function (PF) score on the European organization for research and treatment of cancer quality-of-Life questionnaire Core 30 Items (EORTC-QLQ-C30)
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
Change in global health status (GHS)/QoL scale score on the EORTC-QLQ-C30
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
Rate of RBCs transfused per protocol algorithm
Per protocol algorithm
Rate of RBCs transfused per protocol algorithm
Per protocol algorithm
Number of units of RBCs transfused per protocol algorithm
Per protocol algorithm
Number of units of RBCs transfused per protocol algorithm
Per protocol algorithm
Change in hemoglobin levels
Per protocol algorithm
Incidence and severity of treatment emergent serious adverse events (SAEs)
Treatment period and safety follow up period
Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest
Treatment period and safety follow up period
Incidence and severity TEAEs leading to treatment discontinuation
Treatment period and safety follow up period
Change in total CH50
Percent change in total CH50
Concentration of total C5 in plasma
Treatment period and safety follow up period
Concentrations of total pozelimab in serum
Treatment period and safety follow up period
Concentrations of total cemdisiran in plasma
Treatment period
Concentrations of total eculizumab in serum
Treatment period
Concentrations of total ravulizumab in plasma
Treatment period
Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab
Treatment period and safety follow up period
Incidence of treatment emergent ADAs to cemdisiran
Treatment period and safety follow up period
Full Information
NCT ID
NCT05131204
First Posted
November 12, 2021
Last Updated
August 14, 2023
Sponsor
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05131204
Brief Title
Efficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria
Acronym
ACCESS 2
Official Title
A Randomized, Open-Label, Eculizumab and Ravulizumab Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Currently Treated With Eculizumab or Ravulizumab
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision not related to efficacy or safety.
Study Start Date
October 6, 2022 (Actual)
Primary Completion Date
July 12, 2023 (Actual)
Study Completion Date
July 12, 2023 (Actual)
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of the study is:
To evaluate the effect of pozelimab and cemdisiran combination therapy on hemolysis, as assessed by lactate dehydrogenase (LDH), after 36 weeks of treatment, in patients with PNH who switch from eculizumab or ravulizumab therapy versus patients who continue their eculizumab or ravulizumab therapy
The secondary objectives of the study are to:
Evaluate the effect of pozelimab and cemdisiran combination treatment versus anti-C5 standard-of-care treatment (eculizumab or ravulizumab) on the following:
Transfusion requirements and transfusion parameters
Measures of hemolysis: LDH control, breakthrough hemolysis, and inhibition of CH50
Hemoglobin levels
Fatigue as assessed by Clinical Outcome Assessments (COAs)
Health-related quality of life (HRQoL) as assessed by COAs
Safety and tolerability
To assess the concentrations of total pozelimab and either total eculizumab or total ravulizumab in serum and total cemdisiran and total C5 protein in plasma
To assess the immunogenicity of 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 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pozelimab and Cemdisiran
Arm Type
Experimental
Arm Description
Randomized 1:1
Arm Title
Anti-C5 standard-of-care
Arm Type
Experimental
Arm Description
Randomized 1:1
Intervention Type
Drug
Intervention Name(s)
Cemdisiran
Other Intervention Name(s)
ALN-CC5
Intervention Description
Administered per protocol
Intervention Type
Drug
Intervention Name(s)
Eculizumab
Other Intervention Name(s)
Soliris
Intervention Description
Administered per protocol
Intervention Type
Drug
Intervention Name(s)
Pozelimab
Other Intervention Name(s)
REGN3918
Intervention Description
Administered per protocol
Intervention Type
Drug
Intervention Name(s)
Ravulizumab
Other Intervention Name(s)
ALXN1210, Ultomiris
Intervention Description
Administered per protocol
Primary Outcome Measure Information:
Title
Percent change in lactate dehydrogenase (LDH)
Time Frame
From baseline to week 36
Secondary Outcome Measure Information:
Title
Proportion of patients with transfusion avoidance
Description
Patients who do not receive an RBC transfusion as per protocol algorithm based on post baseline hemoglobin values
Time Frame
Day 1 through week 36
Title
Proportion of patients with transfusion avoidance
Description
Patients who do not receive an RBC transfusion as per protocol algorithm based on post baseline hemoglobin values
Time Frame
Week 4 through week 36
Title
Proportion of patients with breakthrough hemolysis
Description
Patients with an increase in LDH with concomitant signs or symptoms associated with hemolysis as described in the protocol
Time Frame
Day 1 through week 36
Title
Proportion of patients with breakthrough hemolysis
Description
Patients with an increase in LDH with concomitant signs or symptoms associated with hemolysis as described in the protocol
Time Frame
Week 4 (day 29) through week 36
Title
Proportion of patients with hemoglobin stabilization
Description
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level as defined in the protocol
Time Frame
Day 1 through week 36
Title
Proportion of patients with hemoglobin stabilization
Description
Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level as defined in the protocol
Time Frame
Week 4 (day 29) through week 36
Title
Proportion of patients with adequate control of LDH
Description
Proportion of patients with adequate control of LDH as defined in the protocol
Time Frame
Day 1 through week 36
Title
Proportion of patients with adequate control of LDH
Description
Proportion of patients with adequate control of LDH as defined in the protocol
Time Frame
Week 8 (day 57) through week 36
Title
Proportion of patients with normalization of LDH
Description
Proportion of patients with normalization of LDH as defined in the protocol
Time Frame
Day 1 through week 36
Title
Proportion of patients with normalization of LDH
Description
Proportion of patients with normalization of LDH as defined in the protocol
Time Frame
Week 8 (day 57) through week 36
Title
Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale
Description
The FACIT-Fatigue is a 13 item, self-administered clinical outcome assessment (COA) assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health related quality of life (QoL) in patients with cancer and other chronic illnesses. The FACIT-Fatigue assesses the level of fatigue using a Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue.
Time Frame
From baseline to week 36
Title
Change in Physical Function (PF) score on the European organization for research and treatment of cancer quality-of-Life questionnaire Core 30 Items (EORTC-QLQ-C30)
Description
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
Time Frame
From baseline to week 36
Title
Change in global health status (GHS)/QoL scale score on the EORTC-QLQ-C30
Description
EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 7 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, sleep and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
Time Frame
From baseline to week 36
Title
Rate of RBCs transfused per protocol algorithm
Description
Per protocol algorithm
Time Frame
Day 1 through week 36
Title
Rate of RBCs transfused per protocol algorithm
Description
Per protocol algorithm
Time Frame
Week 4 through week 36
Title
Number of units of RBCs transfused per protocol algorithm
Description
Per protocol algorithm
Time Frame
Day 1 through week 36
Title
Number of units of RBCs transfused per protocol algorithm
Description
Per protocol algorithm
Time Frame
Week 4 through week 36
Title
Change in hemoglobin levels
Description
Per protocol algorithm
Time Frame
From baseline to week 36
Title
Incidence and severity of treatment emergent serious adverse events (SAEs)
Description
Treatment period and safety follow up period
Time Frame
Up to 88 weeks
Title
Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest
Description
Treatment period and safety follow up period
Time Frame
Up to 88 weeks
Title
Incidence and severity TEAEs leading to treatment discontinuation
Description
Treatment period and safety follow up period
Time Frame
Up to 88 weeks
Title
Change in total CH50
Time Frame
From baseline to week 36
Title
Percent change in total CH50
Time Frame
From baseline to week 36
Title
Concentration of total C5 in plasma
Description
Treatment period and safety follow up period
Time Frame
Through week 62
Title
Concentrations of total pozelimab in serum
Description
Treatment period and safety follow up period
Time Frame
Through week 62
Title
Concentrations of total cemdisiran in plasma
Description
Treatment period
Time Frame
Through week 32
Title
Concentrations of total eculizumab in serum
Description
Treatment period
Time Frame
Through week 40
Title
Concentrations of total ravulizumab in plasma
Description
Treatment period
Time Frame
Through week 44
Title
Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab
Description
Treatment period and safety follow up period
Time Frame
Through week 62
Title
Incidence of treatment emergent ADAs to cemdisiran
Description
Treatment period and safety follow up period
Time Frame
Through week 62
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
Treated with eculizumab or ravulizumab prior to screening visit as described in the protocol Note: Biosimilars are not permitted, unless approved by the Sponsor
Key Exclusion Criteria:
Patients with a screening LDH >1.5 × ULN who have not taken their C5 inhibitor within the labeled dose interval at the dose prior to the screening LDH assessment
Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
Body weight < 40 kilograms at screening visit
Any use of complement inhibitor therapy other than eculizumab or ravulizumab in the 26 weeks prior to the screening visit or planned use during the study with the exception of study treatments
Not meeting meningococcal vaccination requirements for eculizumab or ravulizumab according to the current local prescribing information (where available) and at a minimum documentation of meningococcal vaccination within 5 years prior to screening visit.
Any contraindication for receiving Neisseria meningitidis vaccination.
Positive for hepatitis B, and/ or hepatitis C as described in the protocol
History of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
Participation in another interventional clinical study (except R3918-PNH-2021) or use of any experimental therapy within 30 days before screening visit or within 5 half-lives of that investigational product, whichever is greater, with the exception of eculizumab or ravulizumab.
Patients with functional or anatomic asplenia
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
Regeneron Research Facility
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
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
Efficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria
We'll reach out to this number within 24 hrs