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

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03748823
• Other study ID #: ALXN1210-PNH-303
• Secondary ID: 2017-002370-39
• Status: Completed
• Phase: Phase 3
• Start date: February 19, 2019
• Est. completion date: August 31, 2023

Study information

• Verified date: June 2024
• Source: Alexion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 139
• Est. completion date: August 31, 2023
• Est. primary completion date: February 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Intervention

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

Biological:
• Ravulizumab
Administered by IV infusion. Ravulizumab IV doses will be based on participant body weight.

Locations

Country	Name	City	State
Australia	Research Site	Liverpool
Australia	Research Site	Parkville
Austria	Research Site	Vienna
Belgium	Research Site	Antwerpen
Belgium	Research Site	Bruxelles
Belgium	Research Site	Hasselt
Belgium	Research Site	Leuven
Brazil	Research Site	Botucatu
Brazil	Research Site	Ribeirão Preto
Brazil	Research Site	Rio De De Janeiro
Brazil	Research Site	Salvador
Brazil	Research Site	Sao Paulo
Brazil	Research Site	São Paulo
Canada	Research Site	Toronto	Ontario
Finland	Research Site	Helsinki
France	Research Site	Amiens
France	Research Site	Brest
France	Research Site	Lille
France	Research Site	Montpellier Cedex 5
France	Research Site	Nantes cedex 01
France	Research Site	Nice
France	Research Site	Paris
France	Research Site	Pessac
France	Research Site	Pierre Benite Cedex
France	Research Site	Poitiers
France	Research Site	Rennes Cedex 9
France	Research Site	Strasbourg
France	Research Site	Tours
Italy	Research Site	Catania
Italy	Research Site	Milano
Italy	Research Site	Roma
Italy	Research Site	Rome
Netherlands	Research Site	Maastricht
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint-Petersburg
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Donostia
Spain	Research Site	Las Palmas de Gran Canaria
Spain	Research Site	Madrid
Spain	Research Site	Majadahonda
Spain	Research Site	Sevilla
Sweden	Research Site	Uppsala
Turkey	Research Site	Adana
Turkey	Research Site	Istambul
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
United States	Research Site	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Finland,  France,  Italy,  Netherlands,  Russian Federation,  Spain,  Sweden,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ctrough Serum Concentration of Ravulizumab		Predose at Day 71
Secondary	Ctrough Serum Concentration of Ravulizumab at Day 351		Predose at Day 351
Secondary	Free Serum Complement Component 5 (C5) Concentrations at Day 71		Predose at Day 71
Secondary	Free Serum Complement Component 5 (C5) Concentrations at Day 351		Predose at Day 351
Secondary	Percent Change From Baseline in Lactate Dehydrogenase (LDH) Levels at Day 71	Baseline was defined as the last assessment prior to first study drug dose. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.	Baseline, Day 71
Secondary	Percent Change From Baseline in Lactate Dehydrogenase Levels at Day 351	Subcutaneous baseline was defined as the last assessment prior to first dose of subcutaneous treatment. Lactate dehydrogenase samples impacted by tabletop hemolysis were excluded from the analysis.	Baseline, Day 351
Secondary	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Subscale Version 4 Score at Day 71	FACIT-fatigue subscale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of study drug.	Baseline, Day 71
Secondary	Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale Version 4 Score at Day 351	FACIT-fatigue scale is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the preceding 7 days; total scores range from 0 to 52 with higher score indicating better health-related quality of life. Baseline was defined as the last non-missing value prior to the first dose of subcutaneous treatment.	Baseline, Day 351
Secondary	Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 71	The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.	Baseline, Day 71
Secondary	Change From Baseline in Treatment Administration Satisfaction Questionnaire (TASQ) Score at Day 351	The Treatment Administration Satisfaction Questionnaire (TASQ) is a 19-item questionnaire that assesses treatment administration satisfaction across 5 domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each domain offers up to 5 response options; lower scores indicate a more positive response. Scoring is completed by summing each of the 5 domains. Total TASQ scores during the study ranged from 0 to 367, with a lower score indicating greater satisfaction with treatment administration.	Baseline, Day 351
Secondary	Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 71	Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 grams/deciliter (g/dL)], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH =2*upper limit of normal (ULN). Denominator for a percentage was participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess breakthrough hemolysis.	Baseline up to Day 71
Secondary	Percentage of Participants Who Experienced Breakthrough Hemolysis up to Day 351	Breakthrough hemolysis was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 g/dL], major adverse vascular event [MAVE, including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH =2*ULN. Denominator for a percentage was participants with at least one post-baseline data for the period.	Baseline up to Day 351
Secondary	Percentage of Participants Who Achieved Transfusion Avoidance up to Day 71	Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Percentages are based on participants with any post-baseline data for the period. For Through Day 71, only visits with data were used to assess transfusion avoidance.	Baseline up to Day 71
Secondary	Percentage of Participants Who Achieved Transfusion Avoidance up to Day 351	Transfusion Avoidance was defined as participants who remained transfusion free and did not require a transfusion after the first dose of study drug through the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period.	Baseline up to Day 351
Secondary	Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 71	Stabilized hemoglobin (SHg) was defined as the avoidance of a =2 g/dL decrease in hemoglobin level from Baseline (defined as the last assessment prior to the first dose of the study drug) in the absence of transfusion to the end of the period of interest. Percentages were based on participants with at least one post-baseline data for the period. For Through Day 71, only visits with data were used to assess SHg.	Baseline up to Day 71
Secondary	Percentage of Participants Who Maintained Stabilized Hemoglobin up to Day 351	SHg was defined as the avoidance of a =2 g/dL decrease in hemoglobin level from SC Baseline (defined as the last assessment prior to the first dose of SC treatment) in the absence of transfusion to the end of the period of interest. Denominator for a percentage was participants with at least one post-baseline data for the period. Visits were based on the number of days since first dose of SC treatment.	Baseline up to Day 351