Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab

Alexion Pharmaceuticals

Status and phase: Completed; Phase 4

Conditions: Paroxysmal Nocturnal Hemoglobinuria

Treatments: Biological: Eculizumab; Biological: Ravulizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04320602

ALXN1210-PNH-401

2019-003440-74 (EudraCT Number)

Details and patient eligibility

About

The primary purpose of this study is to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab in participants who are prescribed and are receiving a higher than approved dose of eculizumab to treat paroxysmal nocturnal hemoglobinuria (PNH).

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation of red blood cells and white blood cells, with granulocyte or monocyte clone size of ≥ 5%.
2. Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening.
3. LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening.
4. To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infections within 3 years prior to initiating study drug.
5. Body weight ≥ 40 kilograms.

Key Exclusion Criteria:

1. History of major adverse vascular events within 6 months of Day 1.

2. History of bone marrow transplantation.

3. Lymphoma, leukemia, myelodysplastic syndrome, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.

4. Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.

5. Concomitant use of any of the following medications and not on a stable regimen (as judged by the Investigator) for the time period indicated prior to Screening:

   • Erythropoietin or immunosuppressants for at least 8 weeks
   • Systemic corticosteroids for at least 4 weeks
   • Vitamin K antagonists (for example, warfarin) with a stable international normalized ratio level for at least 4 weeks
   • Iron supplements or folic acid for 4 weeks

6. Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.

7. More than 1 LDH value > 2 × ULN within the 6 months prior to Day 1.

8. Platelet count < 30,000/cubic millimeter (30 × 10^9/Liter [L]) at Screening.

9. Absolute neutrophil count < 500/microliter (0.5 × 10^9/L) at Screening.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Ravulizumab

Experimental group

Description:

Participants will receive eculizumab during the 3-month Screening Period. Participants will then switch over to and receive weight-based doses of ravulizumab for the duration of the study Treatment Period (351 days).

Treatment:

Biological: Ravulizumab

Biological: Eculizumab