ALXN1210 Versus Eculizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab

Alexion Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)

Treatments: Biological: Ravulizumab; Biological: Eculizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03056040

2016-002026-36 (EudraCT Number)

ALXN1210-PNH-302

Details and patient eligibility

About

The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult participants with PNH who were clinically stable after having been treated with eculizumab for at least 6 months.

Full description

The study consisted of a 4-week Screening Period and a 26-week Randomized Treatment Period (Primary Evaluation Period). After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants will receive ravulizumab for up to 4 years.

Enrollment: 197 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female ≥18 years of age.
2. Treated with eculizumab for PNH for at least 6 months prior to Day 1.
3. Lactate dehydrogenase level ≤1.5 times the upper limit of normal (ULN) at screening.
4. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.
5. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
6. Female participants of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
7. Willing and able to give written informed consent and comply with study visit schedule.

Exclusion criteria

1. History of bone marrow transplantation.
2. Body weight <40 kilograms at screening.
3. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation.
4. Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleeding, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, or coexisting chronic anemia unrelated to PNH).
5. Female participants who are pregnant, breastfeeding, or who have a positive pregnancy test at screening or Day 1.
6. Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study treatment on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Parallel Assignment

Masking: None (Open label)

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197 participants in 2 patient groups

Ravulizumab

Experimental group

Description:

On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 milligrams (mg). Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 4 years.

Treatment:

Biological: Ravulizumab

Eculizumab

Active Comparator group

Description:

Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 4 years.

Treatment:

Biological: Eculizumab

Biological: Ravulizumab