Clinical trial NCT03748823: Ravulizumab Subcutaneous (SC) Versus Ravulizumab Intravenous (IV) in Adults With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: PNH
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-11-21
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Ctrough Serum Concentration of Ravulizumab
timeFrame: Predose at Day 71
Secondary outcomes:
measure: Ctrough Serum Concentration of Ravulizumab at Day 351
timeFrame: Predose at Day 351
measure: Free Serum Complement Component 5 (C5) Concentrations at Day 71
timeFrame: Predose at Day 71
measure: Free Serum Complement Component 5 (C5) Concentrations at Day 351
timeFrame: Predose at Day 351
measure: Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71
timeFrame: Baseline, Day 71
measure: Percent Change From Baseline in LDH Levels at Day 351
timeFrame: Baseline, Day 351
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71
timeFrame: Baseline, Day 71
measure: Change From Baseline in FACIT-Fatigue Scale Version 4 Score at Day 351
timeFrame: Baseline, Day 351
measure: Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71
timeFrame: Baseline, Day 71
measure: Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351
timeFrame: Baseline, Day 351
measure: Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71
timeFrame: Baseline up to Day 71
measure: Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351
timeFrame: Baseline up to Day 351
measure: Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71
timeFrame: Baseline up to Day 71
measure: Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351
timeFrame: Baseline up to Day 351
measure: Percentage of Participants Who Maintained Stabilized Hemoglobin (SHg) up to Day 71
timeFrame: Baseline up to Day 71
measure: Percentage of Participants Who Maintained SHg up to Day 351
timeFrame: Baseline up to Day 351
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Liverpool
country: Australia
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: Vienna
country: Austria
facility: Research Site
city: Antwerpen
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Hasselt
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Botucatu
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Rio De De Janeiro
country: Brazil
facility: Research Site
city: Salvador
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Helsinki
country: Finland
facility: Research Site
city: Amiens
country: France
facility: Research Site
city: Brest
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Montpellier Cedex 5
country: France
facility: Research Site
city: Nantes cedex 01
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Pessac
country: France
facility: Research Site
city: Pierre Benite Cedex
country: France
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Rennes Cedex 9
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Tours
country: France
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Maastricht
country: Netherlands
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Donostia
country: Spain
facility: Research Site
city: Las Palmas de Gran Canaria
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Istambul
country: Turkey
facility: Research Site
city: İstanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
Study officials:
References:
citation: Yenerel MN, Sicre de Fontbrune F, Piatek C, Sahin F, Fureder W, Ortiz S, Ogawa M, Ozol-Godfrey A, Sierra JR, Szer J. Phase 3 Study of Subcutaneous Versus Intravenous Ravulizumab in Eculizumab-Experienced Adult Patients with PNH: Primary Analysis and 1-Year Follow-Up. Adv Ther. 2023 Jan;40(1):211-232. doi: 10.1007/s12325-022-02339-3. Epub 2022 Oct 22.