Study to evaluate efficacy and safety of Ravulizumab in adult patients with thrombotc microangiopathy

Phase 1

• Conditions: Trombotic Microangiopathy associated with a trigger; MedDRA version: 20.0Level: PTClassification code 10043645Term: Thrombotic microangiopathySystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 20.0Level: PTClassification code 10062198Term: MicroangiopathySystem Organ Class: 10047065 - Vascular disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-005328-13-IT
• Lead Sponsor: ALEXION PHARMACEUTICALS INCORPORATED

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-08
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 100

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.Diagnosis of TMA (platelet count, LDH, and acute kidney injury) associated with a trigger such as autoimmune, solid organ transplant or drug induced
5.Vaccinated against meningococcal infection (N 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 79
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 21

Exclusion Criteria

1.Any known gene mutation that causes aHUS
2.Postpartum aHUS
3.Known CKD with eGFR = 45 mL/min/1.73 m2 by CKD-EPI equation (Levey, 2009) due to any cause
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
10.Diagnosis of disseminated intravascular coagulation (DIC)
11.Presence of sepsis according 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of ravulizumab versus placebo;Secondary Objective: To assess Safety and tolerability of ravulizumab and additional efficacy measures;Primary end point(s): Complete TMA response;Timepoint(s) of evaluation of this end point: throughout week 26

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Time to complete TMA repsonse<br>2. Hematologic response<br>3. Renal response<br>4. TMA response duration and TMA relapse<br>5. Change in kidney function;Timepoint(s) of evaluation of this end point: Week 26 and Week 52