A Phase 3, Randomized, Parallel-Group, Multicenter, Open-Label Pharmacokinetic, Noninferiority Study of Ravulizumab Administered Subcutaneously Versus Intravenously in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With Eculizumab

Phase 3

Completed

• Conditions: Paroxysmal Nocturnal Hemoglobinuria; red blood cell disorder; 10038158

• Registration Number: NL-OMON52568
• Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 5

Inclusion Criteria

1. Patients must be at least 18 years of age at the time of signing the
informed consent.
2. Treated with eculizumab according to the labeled dosing recommendation for
PNH (900 mg every 14 days ± 2 days) for at least 3 months prior to study entry
with no missed doses within 2 months prior to study entry and no more than 2
doses outside of the visit window.
3. Lactate dehydrogenase levels <= 1.5 × ULN (upper limit of normal), according
to central laboratory, at Screening. Sample must be obtained within 24 hours of
or immediately prior to a scheduled eculizumab dose administration (ie, at
trough eculizumab level).
4. Documented diagnosis of PNH confirmed by high-sensitivity flow cytometry
evaluation (Borowitz, 2010).
5. Vaccinated against meningococcal infections within 3 years prior to, or at
the time of, initiating study drug to reduce the risk of meningococcal
infection (N meningitidis).
6. Body weight > 40 to < 100 kg, and in the opinion of the Investigator, are
likely to remain within this body weight range for the duration of the study.
7. Female patients of childbearing potential and male patients with female
partners of childbearing potential must follow protocol-specified contraception
guidance while on treatment and for at least 8 months after last dose of study
drug.
8. Patients (or their legally authorized representative) must be willing and
able to give written informed consent and to comply with all study visits and
procedures, including self administration of ravulizumab SC doses, and the use
of any data collection device(s) to directly record patient data.

Exclusion Criteria

1. More than 1 LDH value > 2 × ULN within the 3 months prior to study entry.
2. Major adverse vascular event (MAVE) in the 6 months prior to study entry.
3. Platelet count < 30,000/mm3 (30 × 10*9/L) at Screening.
4. Absolute neutrophil count < 500/µL (0.5 × 10*9/L) at Screening.
5. History of bone marrow transplantation.
6. History of N meningitidis infection.
7. History of unexplained infections.
8. Active systemic bacterial, viral, or fungal infection within 14 days prior
to study drug administration on Day 1.
9. Presence of fever >= 38°C (100.4°F) within 7 days prior to study drug
administration on Day 1.
10. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2
antibody titer).
11. History of malignancy within 5 years of Screening with the exception of
nonmelanoma skin cancer or carcinoma in situ of the cervix that has been
treated with no evidence of recurrence.
12. History of or ongoing major cardiac, pulmonary, renal, endocrine, or
hepatic disease (eg, active hepatitis) that, in the opinion of the Investigator
or Sponsor, precludes the patient*s participation in an investigational
clinical study.
13. Unstable medical conditions (eg, myocardial ischemia, active
gastrointestinal bleed, severe congestive heart failure, anticipated need for
major surgery within 6 months of Day 1, coexisting chronic anemia unrelated to
PNH) that would make patients unlikely to tolerate the requirements of the
protocol).
14. History of hypersensitivity to any ingredient contained in the study drug
including hypersensitivity to murine proteins.
15. Female patients who plan to become pregnant or are currently pregnant or
breastfeeding.
16. Female patients who have a positive pregnancy test result at screening or
on Day 1.
17. Known medical or psychological condition(s) or risk factor that, in the
opinion of the Investigator, might interfere with the patient*s full
participation in the study, pose an additional risk for the patient, or
confound the outcome of the study.
18. Known or suspected history of drug or alcohol abuse or dependence within 1
year prior to Screening.
19. Inability to complete the requirements for SC self-administration.
20. Inability to travel to the clinic for specified visits during the
Randomized Treatment Period or fulfil the logistic requirements of study drug.
21. Concomitant use of anticoagulants is prohibited if not on a stable regimen
for at least 2 weeks prior to study entry.
22. Participation in another 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 (except for
participation in observational studies [eg, PNH Registry]).
23. Received any other experimental C5 antagonist at any time.

Study & Design

• Study Type: Interventional
• Study Design: Not specified