Ravulizumab for people with clinical aHUS

Multicenter, Open-label, Single-arm, Post-Marketing Clinical Study to Evaluate the Efficacy and Safety of Ravulizumab in Participants Clinically Diagnosed as Atypical Hemolytic Uremic Syndrome

This study will test whether ravulizumab raises platelet counts in people diagnosed with clinical atypical hemolytic uremic syndrome (aHUS), including those with certain infections (excluding pneumococcal and STEC), pregnancy/postpartum, recent kidney transplant, malignant hypertension, or autoimmune conditions.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Alexion Pharmaceuticals, Inc. (Industry-sponsored)
• Drugs / interventions: ravulizumab
• Locations: 12 sites (Bunkyō City and 11 other locations)
• Trial ID: NCT07308574 on ClinicalTrials.gov

What this trial studies

This is a post-marketing, phase 4 interventional study enrolling participants clinically diagnosed with aHUS to receive ravulizumab. The primary objective is to measure platelet count response after treatment; eligible participants must weigh at least 20 kg and meet laboratory signs of thrombotic microangiopathy such as platelet count <150,000/µL, hemoglobin <10 g/dL, and acute kidney injury by specified creatinine changes. The protocol includes people with complicating conditions (infections except pneumococcal and STEC, pregnancy or postpartum, post-renal transplant, malignant hypertension, or connective tissue diseases) and those whose TMA has not improved after treatment for secondary TMA. Platelet counts and clinical markers of hemolysis and renal function will be followed over time to document response to ravulizumab.

Who should consider this trial

Good fit: Ideal candidates are people with a clinical diagnosis of aHUS who weigh at least 20 kg and show thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury per the study's laboratory criteria, including those with the specified comorbid conditions.

Not a fit: People whose TMA is clearly due to pneumococcal infection or Shiga toxin–producing E. coli, or who do not meet the platelet, anemia, or kidney-injury entry criteria, may be ineligible and unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, ravulizumab could increase platelet counts and help control thrombotic microangiopathy, potentially protecting kidney function and reducing the need for intensive interventions.

How similar studies have performed: Complement C5 inhibitors such as eculizumab and ravulizumab have demonstrated benefit in aHUS in prior clinical trials and real-world experience, supporting this post-marketing evaluation.

Eligibility criteria

Inclusion Criteria:

* Body weight ≥20 kilograms (kg)
* Participants clinically diagnosed as aHUS who have any of diseases/conditions listed below (including participants in whom Thrombotic microangiopathy (TMA) has not been improved even after treatment for the pathogenesis of diagnosed secondary TMA and therefore, diagnosis of aHUS was made).
* Infection (except for pneumococcal infection and Siga toxin-producing Escherichia coli infection)
* During pregnancy or postpartum
* Post-renal transplantation
* Hypertensive crisis/malignant hypertension
* Systemic lupus erythematosus and related diseases (e.g. dermatomyositis, mixed connective tissue disease, etc.)
* Participants with the following three signs:
* Thrombocytopenia: Platelet count \<150,000/microliter (μL)
* Microangiopathic haemolytic anaemia: Hb \< 10 grams per deciliter (g/dL) (\*)
* Acute kidney injury: one of the following is fulfilled; 1. ΔsCr ≥ 0.3 milligrams per deciliter (mg/dL) (within 48 hours), 2. 1.5-fold increase from baseline sCr (within 7 days), 3. urinary output ≤ 0.5 mL/kg/hour for ≥ 6 hours.
* No prior treatment with complement inhibitors.
* The investigator plans to provide the participant with 26-week treatment with ravulizumab in accordance with the treatment policy in clinical practice.
* Ravulizumab treatment is planned to be initiated within 14 days after onset of the latest TMA episode.
* Participants consenting to meningococcal vaccine administration and appropriate antibiotic prophylaxis (if required).

Exclusion Criteria:

* Participants with TTP, STEC-HUS, secondary TMA that is obviously unrelated to complement abnormality.
* Participants with TMA caused by malignant tumors, abnormal Cobalamin C metabolism, Streptococcus pneumoniae, drugs, autoimmune diseases other than systemic lupus erythematosus and related diseases (e.g. scleroderma etc.), or hematopoietic stem cell transplantation
* Participants with pathological complement gene variants (CFH, CFI , CD46 (MCP), C3, CFB, THBD, DGKE) associated with the development of aHUS at enrolment
* Participants with positive anti-factor H antibodies
* More than 14 day from onset of TMA to the planned start of ravulizumab treatment
* Chronic kidney disease or irreversible renal impairment that requires chronic dialysis
* Presence of unresolved meningococcal disease
* Judgement by the investigator that the participant is not eligible for the study

Where this trial is running

Bunkyō City and 11 other locations

• Research Site — Bunkyō City, Japan (Not_yet_recruiting)
• Research Site — Hirakata-shi, Japan (Not_yet_recruiting)
• Research Site — Iruma-Gun, Japan (Recruiting)
• Research Site — Kyoto, Japan (Not_yet_recruiting)
• Research Site — Matsumoto-shi, Japan (Not_yet_recruiting)
• Research Site — Miyazaki, Japan (Not_yet_recruiting)
• Research Site — Nagoya, Japan (Recruiting)
• Research Site — Nara, Japan (Not_yet_recruiting)
• Research Site — Nerima-ku, Japan (Not_yet_recruiting)
• Research Site — Sapporo, Japan (Not_yet_recruiting)
• Research Site — Shinjuku-ku, Japan (Not_yet_recruiting)
• Research Site — Tsu, Japan (Recruiting)

Study contacts

• Study coordinator: Alexion Pharmaceuticals, Inc. (Sponsor)

Conditions aHUS; Atypical Hemolytic Uremic Syndrome; atypical hemolytic uremic syndrome; ravulizumab