A C5 Inhibitor-controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Are Complement Inhibitor Treatment-Naive or Have Not Recently Received Complement Inhibitor Therapy (ACCESS-1)
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| ClinicalTrials.gov Identifier: NCT05133531 |
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Recruitment Status :
Recruiting
First Posted : November 24, 2021
Last Update Posted : April 10, 2024
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Sponsor:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
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Brief Summary:
The study is researching a clinical treatment combination with two experimental drugs called pozelimab and cemdisiran. The study is focused on patients with paroxysmal nocturnal hemoglobinuria (PNH). The aim of the study is to see how safe and effective the pozelimab + cemdisiran combination is for patients with PNH and how the combination compares with 2 existing treatments, one called ravulizumab and the other called eculizumab.
The pozelimab + cemdisiran combination may be referred to as "study drugs". Ravulizumab and eculizumab may also be called the "comparator drug".
The study is looking at several research questions, including:
- How effective is the pozelimab + cemdisiran combination compared to ravulizumab?
- How effective is pozelimab + cemdisiran combination compared to eculizumab?
- What side effects may happen from taking the study drugs?
- How much study drugs are in your blood at different times?
- Whether the body makes antibodies against the study drugs (which could make the study drugs less effective or could lead to side effects)
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Paroxysmal Nocturnal Hemoglobinuria | Drug: Ravulizumab Drug: Pozelimab Drug: Cemdisiran Drug: Eculizumab | Phase 3 |
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 190 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Open-Label, C5 Inhibitor-Controlled Study to Evaluate the Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Are Complement Inhibitor Treatment-Naive or Have Not Recently Received Complement Inhibitor Therapy |
| Actual Study Start Date : | August 1, 2022 |
| Estimated Primary Completion Date : | March 1, 2027 |
| Estimated Study Completion Date : | March 1, 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Paroxysmal nocturnal hemoglobinuria
| Arm | Intervention/treatment |
|---|---|
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Experimental: Cohort A
Randomized 1:1
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Drug: Ravulizumab
Administered Intravenous (IV) per the protocol
Other Names:
Drug: Pozelimab Administered IV and subcutaneous (SC) per the protocol
Other Name: REGN3918 Drug: Cemdisiran Administered SC per the protocol
Other Name: ALN-CC5 |
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Experimental: Cohort B
Randomized 1:1
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Drug: Pozelimab
Administered IV and subcutaneous (SC) per the protocol
Other Name: REGN3918 Drug: Cemdisiran Administered SC per the protocol
Other Name: ALN-CC5 Drug: Eculizumab Administered IV per the protocol
Other Name: Soliris |
Primary Outcome Measures :
- Percent change in lactate dehydrogenase (LDH) [ Time Frame: From baseline to week 26 ]Cohort A
- Transfusion avoidance [ Time Frame: From post-baseline day 1 through week 26 ]Cohort B Not requiring a red blood cell (RBC) transfusion per the protocol
- Maintenance of adequate control of hemolysis [ Time Frame: From week 8 through week 26, inclusive ]Cohort B LDH ≤1.5 × ULN
Secondary Outcome Measures :
- Maintenance of adequate control of hemolysis [ Time Frame: From week 8 through week 26, inclusive ]Cohort A LDH ≤1.5 × ULN
- Breakthrough hemolysis [ Time Frame: From post-baseline day 1 through week 26 ]Cohort A and B LDH ≥2 × ULN per the protocol
- Adequate control of hemolysis [ Time Frame: From week 8 through week 26, inclusive ]Cohort A and B LDH ≤1.5 × ULN
- Hemoglobin stabilization [ Time Frame: From day 1 (post-baseline) through week 26 ]Cohort A and B Patients who do not receive an RBC transfusion and have no decrease in hemoglobin level per the protocol
- Normalization of LDH [ Time Frame: Between week 8 through week 26, inclusive ]Cohort A and B LDH ≤1.0 × ULN per the protocol
- Transfusion avoidance [ Time Frame: Day 1 through week 26 ]Cohort A Not requiring an RBC transfusion as per protocol algorithm based on post-baseline hemoglobin values.
- Change in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale [ Time Frame: From baseline to week 26 ]Cohort A and B FACIT-Fatigue Scale is a 13-item, self-reported PRO measure 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) scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) [ Time Frame: Change from baseline to week 26 ]Cohort A and B 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."
- Change in global health status (GHS)/QoL scale score on the EORTC-QLC-C30 [ Time Frame: From baseline to week 26 ]Cohort A and B 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."
- Percent change in LDH [ Time Frame: From baseline to week 26 ]Cohort B
- Rate of RBC transfused [ Time Frame: Post-baseline Day 1 through week 26 ]Cohort A and B Per protocol algorithm
- Number of units of RBC transfused [ Time Frame: Post-baseline Day 1 through week 26 ]Cohort A and B Per protocol algorithm
- Time to first LDH ≤1.5 × ULN [ Time Frame: Up to Week 26 ]Cohort A and B
- Time to first LDH ≤1.0 × ULN [ Time Frame: Up to Week 26 ]Cohort A and B
- Percentage of days with LDH ≤1.5 × ULN [ Time Frame: Between week 8 and week 26, inclusive ]Cohort A and B
- Change in hemoglobin levels [ Time Frame: From baseline to week 26 ]Cohort A and B
- Incidence and severity of treatment emergent serious adverse events (SAEs) [ Time Frame: Up to 26 weeks ]Cohort A and B
- Incidence and severity of treatment-emergent adverse events (TEAEs) of special interest [ Time Frame: Up to 26 weeks ]Cohort A and B
- Incidence and severity of TEAEs leading to treatment discontinuation [ Time Frame: Up to 26 weeks ]Cohort A and B
- Change in total CH50 [ Time Frame: From baseline to week 26 ]Cohort A and B
- Percent change in total CH50 [ Time Frame: From baseline to week 26 ]Cohort A and B
- Concentration of total C5 in plasma [ Time Frame: Up to 60 weeks ]Cohort A and B
- Concentrations of total pozelimab in serum [ Time Frame: Up to 60 weeks ]Cohort A and B
- Concentrations of cemdisiran in plasma [ Time Frame: Up to 60 weeks ]Cohort A and B
- Concentrations of total ravulizumab in serum [ Time Frame: Up to 34 weeks ]Cohort A
- Concentrations of total eculizumab in serum [ Time Frame: Up to 30 weeks ]Cohort B
- Incidence of treatment emergent anti-drug antibodies (ADAs) to pozelimab [ Time Frame: Up to 52 weeks ]Cohort A and B
- Incidence of treatment emergent ADAs to cemdisiran [ Time Frame: Up to 52 weeks ]Cohort A and B
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria:
- Diagnosis of PNH confirmed by high-sensitivity flow cytometry testing with PNH granulocytes or monocytes as described in the protocol
- Active disease, as defined by the presence of 1 or more PNH-related signs or symptoms as described in the protocol
- LDH level ≥2 × ULN at the screening visit
Key Exclusion Criteria:
- Prior treatment with eculizumab within 3 months prior to screening, ravulizumab within 6 months prior to screening, or other complement inhibitors within 5 half-lives of the respective agent prior to screening
- Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
- Body weight <40 kilograms at screening visit
- Planned use of any complement inhibitor therapy other than study drugs during the treatment period
- Not meeting meningococcal vaccination requirements for ravulizumab (Cohort A) or eculizumab (Cohort B) 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
- Unable to take antibiotics for meningococcal prophylaxis (if required by local ravulizumab [Cohort A] or eculizumab [Cohort B] prescribing information, where available, or national guidelines/local practice or if necessary when vaccination is less than 2 weeks from study treatment initiation)
- Any active, ongoing infection or a recent infection requiring ongoing systemic treatment with antibiotics, antivirals, or antifungals within 2 weeks of screening or during the screening period
- Documented history of active, uncontrolled, ongoing systemic autoimmune diseases
Note: Other protocol-defined Inclusion/ Exclusion Criteria apply
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05133531
Contacts
| Contact: Clinical Trials Administrator | 844-734-6643 | clinicaltrials@regeneron.com |
Locations
Show 48 study locations
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
| Study Director: | Clinical Trial Management | Regeneron Pharmaceuticals |
| Responsible Party: | Regeneron Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT05133531 |
| Other Study ID Numbers: |
R3918-PNH-2021 2020-004486-40 ( EudraCT Number ) |
| First Posted: | November 24, 2021 Key Record Dates |
| Last Update Posted: | April 10, 2024 |
| Last Verified: | September 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) Analytic Code |
| 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. |
| 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 |
| URL: | https://vivli.org/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Regeneron Pharmaceuticals:
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PNH |
Additional relevant MeSH terms:
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Hemoglobinuria Hemoglobinuria, Paroxysmal Proteinuria Urination Disorders Urologic Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Male Urogenital Diseases Urological Manifestations Anemia, Hemolytic |
Anemia Hematologic Diseases Myelodysplastic Syndromes Bone Marrow Diseases Eculizumab Ravulizumab Complement Inactivating Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |