Thrombotic Microangiopathy Clinical Trial
Official title:
A Phase 3, Open-label, Single Arm, Multicenter Study of Ravulizumab in Addition to Best Supportive Care in Pediatric Participants With Thrombotic Microangiopathy (TMA) After Hematopoietic Stem Cell Transplantation (HSCT)
This study will evaluate the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab administered by intravenous infusion to pediatric participants, from 1 month to < 18 years of age, with HSCT-TMA. The treatment period is 26 weeks, followed by a 26-week off-treatment follow-up period.
Status | Recruiting |
Enrollment | 40 |
Est. completion date | May 30, 2025 |
Est. primary completion date | November 29, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 17 Years |
Eligibility | Inclusion Criteria: 1. 1 month of age up to < 18 years of age at the time of signing the informed consent. 2. Received HSCT within the past 12 months. 3. Diagnosis of TMA that persists despite initial management of any triggering condition. 4. Body weight = 5 kilograms. 5. Female participants of childbearing potential and male participants with female partners of childbearing potential must use highly effective contraception starting at Screening and continuing until at least 8 months after the last dose of ravulizumab. 6. Participants must be vaccinated against meningococcal infections if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. Participants must be re-vaccinated against Haemophilus influenzae type b and Streptococcus pneumoniae if clinically feasible, according to institutional guidelines for immune reconstitution after HSCT. All participants should be administered coverage with prophylactic antibiotics according to institutional post-transplant infection prophylaxis guidances, including coverage against Neisseria meningitidis for at least 2 weeks after meningococcal vaccination. Participants who cannot receive meningococcal vaccine should receive antibiotic prophylaxis coverage against Neisseria meningitidis the entire Treatment Period and for 8 months following the final dose of ravulizumab. Exclusion Criteria: 1. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' deficiency (activity < 5%). 2. Known Shiga toxin-related hemolytic uremic syndrome. 3. Positive direct Coombs test. 4. Diagnosis or suspicion of disseminated intravascular coagulation. 5. Known bone marrow/graft failure. 6. Diagnosis of veno-occlusive disease (VOD). 7. Human immunodeficiency virus (HIV) infection (evidenced by HIV-1 or HIV-2 antibody titer). 8. Unresolved meningococcal disease. 9. Presence of sepsis requiring vasopressor support. 10. Pregnancy or breastfeeding. 11. Hypersensitivity to murine proteins or to 1 of the excipients of Ravulizumab. 12. Previously or currently treated with a complement inhibitor. |
Country | Name | City | State |
---|---|---|---|
France | Research Site | BRON Cedex | |
France | Research Site | Nantes cedex 01 | |
France | Research Site | Paris | |
France | Research Site | Paris | |
France | Research Site | Strasbourg Cedex 2 | |
France | Research Site | Vandoeuvre-Les-Nancy | |
Germany | Research Site | Berlin | |
Germany | Research Site | Freiburg | |
Germany | Research Site | Halle (Saale) | |
Germany | Research Site | Tuebingen | |
Germany | Research Site | Wuerzburg | |
Israel | Research Site | Haifa | |
Israel | Research Site | Jerusalem | |
Israel | Research Site | Petach-Tikva | |
Israel | Research Site | Ramat Gan | |
Italy | Research Site | Bologna | |
Italy | Research Site | Brescia | |
Italy | Research Site | Firenze | |
Italy | Research Site | Genova | |
Italy | Research Site | Monza | |
Italy | Research Site | Pavia | |
Italy | Research Site | Roma | |
Italy | Research Site | Roma | |
Italy | Research Site | Torino | |
Italy | Research Site | Verona | |
Japan | Research Site | Fukuoka-shi | |
Japan | Research Site | Fukushima-shi | |
Japan | Research Site | Kobe-shi | |
Japan | Research Site | Nagoya-shi | |
Japan | Research Site | Osaka-shi | |
Japan | Research Site | Osakasayama | |
Japan | Research Site | Saitama-Shi | |
Japan | Research Site | Setagaya-ku | |
Korea, Republic of | Research Site | Goyang-si | |
Korea, Republic of | Research Site | Seoul | |
Korea, Republic of | Research Site | Seoul | |
Korea, Republic of | Research Site | Seoul | |
Korea, Republic of | Research Site | Seoul | |
Korea, Republic of | Research Site | Seoul | |
Spain | Research Site | Barcelona | |
Spain | Research Site | Barcelona | |
Spain | Research Site | Esplugues de Llobregat | |
Spain | Research Site | Madrid | |
Spain | Research Site | Salamanca | |
Spain | Research Site | Valencia | |
United Kingdom | Research Site | Birmingham | |
United Kingdom | Research Site | Bristol | |
United Kingdom | Research Site | Leeds | |
United Kingdom | Research Site | London | |
United Kingdom | Research Site | Newcastle Upon Tyne | |
United States | Research Site | Akron | Ohio |
United States | Research Site | Atlanta | Georgia |
United States | Research Site | Aurora | Colorado |
United States | Research Site | Birmingham | Alabama |
United States | Research Site | Charlotte | North Carolina |
United States | Research Site | Chicago | Illinois |
United States | Research Site | Cleveland | Ohio |
United States | Research Site | Dallas | Texas |
United States | Research Site | Duarte | California |
United States | Research Site | Fort Worth | Texas |
United States | Research Site | Louisville | Kentucky |
United States | Research Site | Madison | Wisconsin |
United States | Research Site | Minneapolis | Minnesota |
United States | Research Site | Phoenix | Arizona |
United States | Research Site | Portland | Oregon |
United States | Research Site | Salt Lake City | Utah |
United States | Research Site | San Francisco | California |
United States | Research Site | Tucson | Arizona |
United States | Research Site | Valhalla | New York |
Lead Sponsor | Collaborator |
---|---|
Alexion Pharmaceuticals, Inc. |
United States, France, Germany, Israel, Italy, Japan, Korea, Republic of, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | TMA Response | 26 weeks (treatment period) | ||
Secondary | Time To TMA Response | 26 weeks (treatment period) | ||
Secondary | TMA Relapse | Follow Up period (183-365 Days after start of study medication) | ||
Secondary | Overall Survival | 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) | ||
Secondary | Hematologic Response | Hematologic Response as assessed by blood tests to measure lactate dehydrogenase (LDH) and platelet count.
If baseline platelet count = 50,000/mm3, all of the following criteria must be met: - Absolute platelet count > 50,000/mm3 without platelet transfusion support during the prior 7 days [or] If baseline platelet count > 50,000/mm3, all of the following criteria must be met: - = 50% increase in platelet count compared to baseline value Normalization of LDH and absence of schistocytes |
26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) | |
Secondary | Proportion of Participants with Platelet Response = 100,000/mm^3 without transfusion support | 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) | ||
Secondary | Number of Participants with a Change from Baseline in TMA-associated Organ Dysfunction in Renal System, Cardiovascular System, Pulmonary System, CNS, and GI System. | 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period)] | ||
Secondary | Proportion of Participants who die due to any cause during the study, with the exception of death due to underlying disease progression or relapse | 26 weeks (treatment period) and 52 weeks (includes treatment period and off-treatment follow-up period) |
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