Ravulizumab dose optimization

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Radboud universitair medisch centrum Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

12 May 2025 → ongoing

Decision date (initial)

2025-02-17

Transition trial

No

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The main objective is to describe the effectiveness of individualized dosing of ravulizumab compared to standard dosing of ravulizumab in adult PNH patients.

Secondary objectives 4

1. To describe the proportion of patients with breakthrough hemolysis
2. To evaluate changes patient preference for dosing strategy
3. To evaluate transfusion requirements between both dosing strategies
4. To evaluate differences in treatment costs between both dosing strategies

Conditions and MedDRA coding

Paroxysmal nocturnal hemoglobinuria (PNH)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. The patient is eligible for treatment with ravulizumab in line with relevant Dutch guidelines or is already being treated with ravulizumab according to the label and Dutch guidelines.
2. Willing to provide written informed consent
3. 16 years or older

Exclusion criteria 6

1. Patients with thrombosis during treatment with complement inhibitors in the medical history
2. Patients with other concomitant hematological diseases, with the exception for aplastic anemia/PNH
3. Unstable medical conditions (e.g. myocardial infarction, bleeding)
4. Pregnant or lactating patients
5. An LDH >1.5x ULN during the 8 weeks prior to screening for inclusion
6. Use of high dose corticosteroids(defined as >30mg prednisolone equivalent daily during the 8 weeks prior to the screening for inclusion)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of change in LDH compared to baseline LDH between standard dosing and individualized dosing
2. Difference in percentage target attainment (Ravulizumab concentration >100 mg/L) between the standard dosing regimen and the individualized dosing regimen

Secondary endpoints 4

1. The proportion of patients with breakthrough hemolysis, defined as at least 1 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 [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2× the ULN after prior reduction of LDH to <1.5× the ULN on treatment
2. Quality of life assessed with the FACIT-Fatigue Scale and patient preference
3. Differences between number of transfusions between both dosing strategies
4. Differences in cumulative ravulizumab dose over 52 weeks, number of infusions and appointments with the physician as surrogate marker for treatment costs.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Radboud universitair medisch centrum Stichting

Sponsor organisation

Radboud universitair medisch centrum Stichting

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Saskia Langemeijer

Public contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Saskia Langemeijer

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications