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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03748823




Registration number
NCT03748823
Ethics application status
Date submitted
19/11/2018
Date registered
21/11/2018
Date last updated
19/09/2024

Titles & IDs
Public title
Ravulizumab Subcutaneous (SC) Versus Ravulizumab Intravenous (IV) in Adults With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab
Scientific 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
Secondary ID [1] 0 0
2017-002370-39
Secondary ID [2] 0 0
ALXN1210-PNH-303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Ravulizumab OBDS
Treatment: Other - Ravulizumab

Experimental: Ravulizumab SC Treatment Group - 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.

Active comparator: Ravulizumab IV Treatment Group - 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.


Other interventions: Ravulizumab OBDS
The ravulizumab OBDS is a biological-device combination product consisting of a prefilled cartridge containing ravulizumab SC and an on-body injector.

Treatment: Other: Ravulizumab
Administered by IV infusion. Ravulizumab IV doses will be based on participant body weight.
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Ctrough Serum Concentration of Ravulizumab
Timepoint [1] 0 0
Predose at Day 71
Secondary outcome [1] 0 0
Ctrough Serum Concentration of Ravulizumab at Day 351
Timepoint [1] 0 0
Predose at Day 351
Secondary outcome [2] 0 0
Free Serum Complement Component 5 (C5) Concentrations at Day 71
Timepoint [2] 0 0
Predose at Day 71
Secondary outcome [3] 0 0
Free Serum Complement Component 5 (C5) Concentrations at Day 351
Timepoint [3] 0 0
Predose at Day 351
Secondary outcome [4] 0 0
Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71
Timepoint [4] 0 0
Baseline, Day 71
Secondary outcome [5] 0 0
Percent Change From Baseline in Lactate Dehydrogenase Levels at Day 351
Timepoint [5] 0 0
Baseline, Day 351
Secondary outcome [6] 0 0
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71
Timepoint [6] 0 0
Baseline, Day 71
Secondary outcome [7] 0 0
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Version 4 Score at Day 351
Timepoint [7] 0 0
Baseline, Day 351
Secondary outcome [8] 0 0
Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71
Timepoint [8] 0 0
Baseline, Day 71
Secondary outcome [9] 0 0
Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351
Timepoint [9] 0 0
Baseline, Day 351
Secondary outcome [10] 0 0
Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71
Timepoint [10] 0 0
Baseline up to Day 71
Secondary outcome [11] 0 0
Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351
Timepoint [11] 0 0
Baseline up to Day 351
Secondary outcome [12] 0 0
Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71
Timepoint [12] 0 0
Baseline up to Day 71
Secondary outcome [13] 0 0
Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351
Timepoint [13] 0 0
Baseline up to Day 351
Secondary outcome [14] 0 0
Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 71
Timepoint [14] 0 0
Baseline up to Day 71
Secondary outcome [15] 0 0
Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 351
Timepoint [15] 0 0
Baseline up to Day 351

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/02/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/08/2023
Sample size
Target
Accrual to date
Final
139
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Liverpool
Recruitment hospital [2] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
Austria
State/province [2] 0 0
Vienna
Country [3] 0 0
Belgium
State/province [3] 0 0
Antwerpen
Country [4] 0 0
Belgium
State/province [4] 0 0
Bruxelles
Country [5] 0 0
Belgium
State/province [5] 0 0
Hasselt
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Brazil
State/province [7] 0 0
Botucatu
Country [8] 0 0
Brazil
State/province [8] 0 0
Ribeirão Preto
Country [9] 0 0
Brazil
State/province [9] 0 0
Rio De De Janeiro
Country [10] 0 0
Brazil
State/province [10] 0 0
Salvador
Country [11] 0 0
Brazil
State/province [11] 0 0
Sao Paulo
Country [12] 0 0
Brazil
State/province [12] 0 0
São Paulo
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Finland
State/province [14] 0 0
Helsinki
Country [15] 0 0
France
State/province [15] 0 0
Amiens
Country [16] 0 0
France
State/province [16] 0 0
Brest
Country [17] 0 0
France
State/province [17] 0 0
Lille
Country [18] 0 0
France
State/province [18] 0 0
Montpellier Cedex 5
Country [19] 0 0
France
State/province [19] 0 0
Nantes cedex 01
Country [20] 0 0
France
State/province [20] 0 0
Nice
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
France
State/province [22] 0 0
Pessac
Country [23] 0 0
France
State/province [23] 0 0
Pierre Benite Cedex
Country [24] 0 0
France
State/province [24] 0 0
Poitiers
Country [25] 0 0
France
State/province [25] 0 0
Rennes Cedex 9
Country [26] 0 0
France
State/province [26] 0 0
Strasbourg
Country [27] 0 0
France
State/province [27] 0 0
Tours
Country [28] 0 0
Italy
State/province [28] 0 0
Catania
Country [29] 0 0
Italy
State/province [29] 0 0
Milano
Country [30] 0 0
Italy
State/province [30] 0 0
Roma
Country [31] 0 0
Italy
State/province [31] 0 0
Rome
Country [32] 0 0
Netherlands
State/province [32] 0 0
Maastricht
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Ekaterinburg
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Moscow
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Saint-Petersburg
Country [36] 0 0
Spain
State/province [36] 0 0
Badalona
Country [37] 0 0
Spain
State/province [37] 0 0
Barcelona
Country [38] 0 0
Spain
State/province [38] 0 0
Donostia
Country [39] 0 0
Spain
State/province [39] 0 0
Las Palmas de Gran Canaria
Country [40] 0 0
Spain
State/province [40] 0 0
Madrid
Country [41] 0 0
Spain
State/province [41] 0 0
Majadahonda
Country [42] 0 0
Spain
State/province [42] 0 0
Sevilla
Country [43] 0 0
Sweden
State/province [43] 0 0
Uppsala
Country [44] 0 0
Turkey
State/province [44] 0 0
Adana
Country [45] 0 0
Turkey
State/province [45] 0 0
Istambul
Country [46] 0 0
Turkey
State/province [46] 0 0
Istanbul
Country [47] 0 0
Turkey
State/province [47] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Alexion Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03748823
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03748823