Efficacy and Safety of the Combination of Pozelimab and Cemdisiran Versus Continued Eculizumab or Ravulizumab Treatment in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (ACCESS 2)

Regeneron Pharmaceuticals

Status and phase: Terminated; Phase 3

Conditions: Paroxysmal Nocturnal Hemoglobinuria

Treatments: Drug: Cemdisiran; Drug: Eculizumab; Drug: Pozelimab; Drug: Ravulizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05131204

2020-002761-33 (EudraCT Number)

R3918-PNH-2022

Details and patient eligibility

About

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

Enrollment: 3 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Diagnosis of PNH confirmed by a history of high-sensitivity flow cytometry from prior testing
2. 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:

1. 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
2. Receipt of an organ transplant, history of bone marrow transplantation or other hematologic transplant
3. Body weight < 40 kilograms at screening visit
4. 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
5. 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.
6. Any contraindication for receiving Neisseria meningitidis vaccination.
7. Positive for hepatitis B, and/ or hepatitis C as described in the protocol
8. 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
9. 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.
10. Patients with functional or anatomic asplenia

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3 participants in 2 patient groups

Pozelimab and Cemdisiran

Experimental group

Description:

Randomized 1:1

Treatment:

Drug: Ravulizumab

Drug: Pozelimab

Drug: Eculizumab

Drug: Cemdisiran

Anti-C5 standard-of-care

Experimental group

Description:

Randomized 1:1

Treatment:

Drug: Ravulizumab

Drug: Eculizumab