Ravulizumab Subcutaneous (SC) Versus Ravulizumab Intravenous (IV) in Adults With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab

Alexion Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Paroxysmal Nocturnal Hemoglobinuria

Treatments: Biological: Ravulizumab; Combination Product: Ravulizumab OBDS

Study type: Interventional

Funder types: Industry

Identifiers

NCT03748823

ALXN1210-PNH-303

2017-002370-39 (EudraCT Number)

Details and patient eligibility

About

The primary objective of this study is to evaluate pharmacokinetics (PK) of ravulizumab administered subcutaneously via an on-body delivery system (OBDS) compared with intravenously administered ravulizumab in adult participants with PNH who are clinically stable on eculizumab for at least 3 months prior to study entry.

Full description

The study will consist of up to a 30-day Screening Period, a 10-week Randomized Treatment Period, and an Extension Period of up to 172 weeks.

Enrollment: 139 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female ≥18 years of age
• Treated with eculizumab for PNH for at least 3 months prior to Day 1
• LDH level ≤1.5 × upper limit of normal (ULN) at screening
• PNH diagnosis confirmed by documented high-sensitivity flow cytometry.
• Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
• Body weight ≥40 to <100 kilogram (kg)
• 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.
• Willing and able to give written informed consent and comply with study visit schedule.

Exclusion criteria

• More than 1 LDH value > 2 × ULN within the 3 months prior to study entry
• History of bone marrow transplantation.
• History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the Investigator or Sponsor, would preclude participation.
• Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH).
• Females who are pregnant, breastfeeding or who have a positive pregnancy test at screening or Day 1.
• Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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139 participants in 2 patient groups

Ravulizumab SC Treatment Group

Experimental group

Description:

In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by SC maintenance doses of ravulizumab administered via the ravulizumab OBDS on Day 15 and every week (qw) thereafter for a total of 10 weeks of study treatment. In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.

Treatment:

Combination Product: Ravulizumab OBDS

Biological: Ravulizumab

Ravulizumab IV Treatment Group

Active Comparator group

Description:

In the Randomized Treatment Period, participants will receive an IV loading dose of ravulizumab on Day 1 followed by IV maintenance doses of ravulizumab on Day 15. In the Extension Period, ravulizumab SC will be administered via the ravulizumab OBDS from Day 71 qw through Day 1274.

Treatment:

Combination Product: Ravulizumab OBDS

Biological: Ravulizumab