Ravulizumab for Thrombotic Microangiopathy

Recruiting at 232 trial locations

Overseen By Alexion Pharmaceuticals, Inc. (Sponsor)

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion

Must not be taking: Complement inhibitors

Disqualifiers: HIV, Pregnancy, Heart failure, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

146 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab in adult and adolescent participants with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA). In Stage 1, an open-label, single-arm period, the dosing regimen will be confirmed. In Stage 2, participants will be randomized to receive either blinded ravulizumab plus best supportive care or matching placebo plus best supportive care. The treatment period is 26 weeks (open-label for Stage 1, and randomized, double-blind, and placebo-controlled for Stage 2) followed by a 26-week follow-up period.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What makes the drug Ravulizumab unique for treating thrombotic microangiopathy?

Ravulizumab is unique because it is a long-acting medication that requires less frequent dosing compared to other treatments, which can improve convenience and adherence for patients. It works by inhibiting a part of the immune system called the complement system, which is involved in the disease process of thrombotic microangiopathy. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults and teens (12+) who've had a stem cell transplant in the last year and are now facing a complication called TMA that hasn't improved after initial treatment. They must weigh at least 30 kg, be vaccinated against meningococcal infections or on antibiotics if they can't get the vaccine, and use effective birth control if necessary. People with certain heart conditions, severe infections, HIV, or previous complement inhibitor treatments can't join.

Inclusion Criteria

My TMA diagnosis has lasted for over 72 hours despite treatment.

I am vaccinated against meningococcal infections or taking antibiotics if I can't be vaccinated.

You have been diagnosed with a condition called thrombotic microangiopathy (TMA) within the last two weeks.

Exclusion Criteria

I am HIV positive.

I have been diagnosed with a blood clotting disorder.

I have an ongoing meningococcal infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Stage 1: Open-label, single-arm period to confirm dosing regimen. Stage 2: Randomized, double-blind, placebo-controlled period with ravulizumab or placebo plus best supportive care

26 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

26 weeks

Treatment Details

Interventions

• Ravulizumab

Trial Overview The study tests Ravulizumab's effectiveness for HSCT-TMA patients. Initially, everyone gets Ravulizumab to confirm dosing (Stage 1). Then participants are randomly assigned to either continue with Ravulizumab plus supportive care or switch to a placebo plus supportive care for six months (Stage 2), followed by another six months of monitoring.

Participant Groups

Group I: Ravulizumab Experimental Treatment 2 Interventions

In Stage 1, all participants will receive open-label ravulizumab plus Best Supportive Care (BSC). In Stage 2, participants will receive blinded ravulizumab plus Best Supportive Care (BSC).

Group II: Placebo Placebo Group 2 Interventions

In Stage 2, participants randomized to the placebo arm will receive matching placebo plus BSC.

Ravulizumab is already approved in United States, European Union for the following indications:

Approved in United States as Ultomiris for:

• Paroxysmal nocturnal hemoglobinuria (PNH)
• Atypical hemolytic uremic syndrome (aHUS)

Approved in European Union as Ultomiris for:

• Paroxysmal nocturnal haemoglobinuria (PNH)

Who Is Running the Clinical Trial?

Alexion

Lead Sponsor

Trials

247

Recruited

38,600+

Marc Dunoyer

Alexion

Chief Executive Officer since 2021

PhD in Molecular Biology, University of Brussels

Christophe Hotermans

Alexion

Chief Medical Officer since 2021

MD, University of Leuven

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Alexion Pharmaceuticals

Lead Sponsor

Trials

231

Recruited

36,700+

Marc Dunoyer

Alexion Pharmaceuticals

Chief Executive Officer since 2021

B.A. in Psychology from the University of New Hampshire

Christophe Hotermans

Alexion Pharmaceuticals

Chief Medical Officer since 2023

MD

Findings from Research

In a study of 54 eyes with macular edema due to branch retinal vein occlusion (BRVO), treatment with ranibizumab resulted in an average improvement of +16.5 letters in visual acuity after 12 months, with 72% of eyes achieving a final best corrected visual acuity (BCVA) of ≥ 4/8 ETDRS.

The treatment involved an average of 4.8 injections of ranibizumab, and significant anatomical improvements were observed, with 33.3% of eyes achieving a central retinal thickness (CRT) of ≤ 250 μm after one year, indicating effective management of macular edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of the first 12 months treatment of macular edema complicating BRVO in patients treated with ranibizumab. Lalinská, L., Krásný, J., Studený, P., et al.[2019]

A 66-year-old patient developed a rapid progression from a thin epiretinal membrane to a macular pucker within 14 days after receiving an intravitreal ranibizumab injection for branch retinal vein occlusion, highlighting a potential complication of this treatment.

Post-treatment monitoring is crucial for patients with branch retinal vein occlusion, particularly those with pre-existing epiretinal membranes, as they may be at higher risk for complications like macular pucker.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid formation of macular pucker following intravitreal ranibizumab injection for branch retinal vein occlusion. Oshiro, A., Imanaga, N., Koizumi, H.[2022]

In a study of 141 patients treated with Razumab for chorioretinal vascular diseases, significant improvements in corrected distance visual acuity (CDVA) and central foveal thickness (CFT) were observed as early as 1 month and maintained at 3 months, indicating its efficacy.

Razumab was found to be safe, with no significant increases in intraocular pressure or evidence of ocular toxicity or systemic adverse events during the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of Razumab® (CESAR) study: Our experience with the world's first biosimilar Ranibizumab. Verma, L., Thulasidas, M., Purohit, A., et al.[2023]

Ranibizumab is more cost-effective than aflibercept for treating visual impairment due to macular edema from branch retinal vein occlusion (BRVO), with a lifetime cost of £15,273 compared to £17,347 for aflibercept.

Patients treated with ranibizumab gained slightly more health benefits, resulting in an incremental increase of 0.0120 quality-adjusted life-years (QALYs) and cost savings of £2074, making it the preferred option from a UK healthcare payer's perspective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Ranibizumab Versus Aflibercept for Macular Edema Secondary to Branch Retinal Vein Occlusion: A UK Healthcare Perspective. Adedokun, L., Burke, C.[2018]

In Turkey, a total of 291 applications for off-label use of anti-VEGF drugs (aflibercept and ranibizumab) and corticosteroid implants for retinal vein occlusion (RVO) were approved in 2018, with aflibercept being the most commonly requested treatment.

As of 2019, a new stepwise therapy protocol was established, requiring the administration of three doses of intravitreal bevacizumab before considering other licensed treatments, which reflects a significant change in treatment practices for RVO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of off-label anti-vascular endothelial growth factor and steroid implant medication uses in macular edema due to retinal vein occlusion in Turkey. Yilmaz, M., Citirik, M., Rahmanlar, H., et al.[2022]

References

1. Czech Republic pubmed.ncbi.nlm.nih.gov

Results of the first 12 months treatment of macular edema complicating BRVO in patients treated with ranibizumab. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Rapid formation of macular pucker following intravitreal ranibizumab injection for branch retinal vein occlusion. [2022]

3. India pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of Razumab® (CESAR) study: Our experience with the world's first biosimilar Ranibizumab. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Ranibizumab Versus Aflibercept for Macular Edema Secondary to Branch Retinal Vein Occlusion: A UK Healthcare Perspective. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Evaluation of off-label anti-vascular endothelial growth factor and steroid implant medication uses in macular edema due to retinal vein occlusion in Turkey. [2022]