Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger

Thrombotic Microangiopathy Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Ravulizumab in Adult Participants Who Have Thrombotic Microangiopathy Associated With a Trigger

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04743804
• Other study ID #: ALXN1210-TMA-315
• Status: Terminated
• Phase: Phase 3
• Start date: July 1, 2021
• Est. completion date: December 22, 2022

Study information

• Verified date: November 2023
• Source: Alexion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate the efficacy and safety of ravulizumab compared to placebo in adult participants with thrombotic microangiopathy (TMA) associated with a trigger. Participants will be randomized to receive either ravulizumab plus best supportive care or placebo plus best supportive care. The treatment period is 26 weeks followed by a 26-week off-treatment follow-up period.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: December 22, 2022
• Est. primary completion date: November 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 18 years of age or older

2. Body weight = 30 kilograms

3. 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

4. TMA associated with a trigger (autoimmune disease, infection, solid organ transplant, drugs, and malignant hypertension)

5. Vaccinated against meningococcal infection (Neisseria meningitidis), within 3 years prior to, or at the time of, randomization. Participants who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive appropriate prophylactic antibiotics for at least 2 weeks after the vaccination. If participant cannot receive the meningococcal vaccine, then participant must be willing to receive antibiotic prophylaxis coverage against N. meningitidis during the entire Treatment Period and for 8 months following the final dose of study drug. Additional vaccination (Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae) may be considered based on individual patient condition.

Exclusion Criteria:

1. Any known gene mutation that causes atypical hemolytic uremic syndrome (aHUS)

2. Postpartum aHUS

3. Known chronic kidney disease

4. TMA due to hematopoietic stem cell transplantation = 12 months of Screening

5. Primary and secondary glomerular diseases other than lupus

6. Diagnosis of primary antiphospholipid antibody syndrome

7. Shiga toxin-producing Escherichia coli infections including but not limited to Shiga toxin-related hemolytic uremic syndrome

8. Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13) deficiency (activity < 5%)

9. Positive direct Coombs test which in the judgement of the Investigator is indicative of a clinically significant immune-mediated hemolysis not due to TMA

10. Clinical diagnosis of disseminated intravascular coagulation (DIC) in the judgement of the Investigator

11. Presence of sepsis requiring vasopressors within 7 days prior to or during Screening

12. Presence of monoclonal gammopathy including but not limited to multiple myeloma

13. Known bone marrow insufficiency or failure evidenced by cytopenias

14. Unresolved N. meningitidis infection

15. History of malignancy within 5 years of Screening with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence

16. Use of any complement inhibitors within the past 3 years

17. Respiratory failure requiring mechanical ventilation

Related Conditions & MeSH terms

• Thrombotic Microangiopathies
• Thrombotic Microangiopathy
• Vascular Diseases

Intervention

Biological:
• Ravulizumab
Body weight-based doses of ravulizumab will be administered intravenously as loading dose regimen followed by maintenance dosing every 8 weeks.

Other:
• Placebo
Matching placebo
• Best Supportive Care
Participants will receive medications, therapies, and interventions per standard hospital treatment protocols (unless specifically prohibited by the protocol).

Locations

Country	Name	City	State
Belgium	Clinical Trial Site	Bruxelles
Belgium	Clinical Trial Site	Leuven
Belgium	Clinical Trial Site	Liege
Canada	Clinical Trial Site	Montreal
Canada	Clinical Trial Site	Toronto
France	Clinical Trial Site	Bordeaux
France	Clinical Trial Site	Chambery
France	Clinical Trial Site	Lille
France	Clinical Trial Site	Montpellier
France	Clinical Trial Site	Paris
France	Clinical Trial Site	Tours
Italy	Clinical Trial Site	Bergamo
Italy	Clinical Trial Site	Rome
Japan	Clinical Trial Site	Iruma-gun
Japan	Clinical Trial Site	Miyagi
Japan	Clinical Trial Site	Miyazaki City
Japan	Clinical Trial Site	Nagoya
Japan	Clinical Trial Site	Osaka
Japan	Clinical Trial Site	Sapporo
Japan	Clinical Trial Site	Shinjuku-ku
Japan	Clinical Trial Site	Tokyo
Korea, Republic of	Clinical Trial Site	Daegu
Korea, Republic of	Clinical Trial Site	Gwangju
Korea, Republic of	Clinical Trial Site	Seoul
Netherlands	Clinical Trial Site	Amsterdam
Netherlands	Clinical Trial Site	Nijmegen
Spain	Clinical Trial Site	Barcelona
Spain	Clinical Trial Site	Granada
Spain	Clinical Trial Site	Madrid
Taiwan	Clinical Trial Site	Kaohsiung
Taiwan	Clinical Trial Site	Taichung
Taiwan	Clinical Trial Site	Taipei
United Kingdom	Clinical Trial Site	Liverpool
United Kingdom	Clinical Trial Site	London
United Kingdom	Clinical Trial Site	Newcastle
United Kingdom	Clinical Trial Site	Nottingham
United Kingdom	Clinical Trial Site	Oxford
United Kingdom	Clinical Trial Site	Salford
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Cleveland	Ohio
United States	Clinical Trial Site	Columbus	Ohio
United States	Clinical Trial Site	Gainesville	Florida
United States	Clinical Trial Site	Lexington	Kentucky
United States	Clinical Trial Site	Morgantown	West Virginia
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Orange	California
United States	Clinical Trial Site	Philadelphia	Pennsylvania
United States	Clinical Trial Site	Pittsburgh	Pennsylvania
United States	Clinical Trial Site	Salt Lake City	Utah
United States	Clinical Trial Site	Tucson	Arizona
United States	Clinical Trial Site	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26	TMA response required the following: 1) Normalization of platelet count without transfusion support during the prior 7 days. 2) Normalization of LDH. 3) Improvement in glomerular filtration rate (eGFR) of >= 30% compared to baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, and any measurement in between.	Week 26
Secondary	Time to Complete TMA Response	The Kaplan-Meier estimate of time to event of complete TMA response is reported. TMA response required the following: 1) Normalization of platelet count without transfusion support during the prior 7 days. 2) Normalization of LDH. 3) Improvement in eGFR of >= 30% compared to baseline. Participants must meet each TMA criterion at 2 separate assessments obtained at least 24 hours apart, and any measurement in between. Participants who did not have a response were censored at the date of last visit or study discontinuation at the time when the analysis was performed.	Baseline through Week 26
Secondary	Number of Participants With Hematologic Response at Week 26	Hematologic response required the following: (1) Normalization of platelet count without transfusion support during the prior 7 days, and (2) normalization of LDH.	Week 26
Secondary	Number of Participants With Renal Response at Week 26	Renal response is improvement in eGFR of >= 30% compared to baseline. If a participant is on dialysis =5 days prior to the date of eGFR assessment, the eGFR will be set to 10 milliliter/minute/1.73 meter square (mL/min/1.73 m^2) for that assessment. If a participant is on dialysis during the entire 26 week randomized Treatment Period, or through early discontinuation of study drug, then the change in eGFR was not calculated.	Week 26
Secondary	Number of Participants On Dialysis at Week 26		Week 26
Secondary	Change From Baseline in eGFR at Week 26	If a participant is on dialysis during the entire 26 week randomized Treatment Period, or through early discontinuation of study drug, then the change in eGFR was not calculated.	Baseline, Week 26