Ravulizumab in Thrombotic Microangiopathy Associated With a Trigger

Study Identifier:
ALXN1210-TMA-315
ClinicalTrials.gov Identifier:
NCT04743804
EudraCT Identifier:
2020-005328-13
EU CT ID:
N/A
Sponsor:
Alexion Pharmaceuticals, Inc.
Study Contact Information:
N/A
Other

Available Documents

ProtocolStatistical Analysis Plan

Study Details

Medical Condition
  • Thrombotic Microangiopathy
Study Drug
  • Biological: Ravulizumab
Date
Jun 2021 - Dec 2022
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 18+ years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • 18 years of age or older
  • Body weight ≥ 30 kilograms
  • 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
  • TMA associated with a trigger (autoimmune disease, infection, solid organ transplant, drugs, and malignant hypertension)
  • 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
  • Any known gene mutation that causes atypical hemolytic uremic syndrome (aHUS)
  • Postpartum aHUS
  • Known chronic kidney disease
  • TMA due to hematopoietic stem cell transplantation ≤ 12 months of Screening
  • Primary and secondary glomerular diseases other than lupus
  • Diagnosis of primary antiphospholipid antibody syndrome
  • Shiga toxin-producing Escherichia coli infections including but not limited to Shiga toxin-related hemolytic uremic syndrome
  • Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13) deficiency (activity \< 5%)
  • Positive direct Coombs test which in the judgement of the Investigator is indicative of a clinically significant immune-mediated hemolysis not due to TMA
  • Clinical diagnosis of disseminated intravascular coagulation (DIC) in the judgement of the Investigator
  • Presence of sepsis requiring vasopressors within 7 days prior to or during Screening
  • Presence of monoclonal gammopathy including but not limited to multiple myeloma
  • Known bone marrow insufficiency or failure evidenced by cytopenias
  • Unresolved N. meningitidis infection
  • 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
  • Use of any complement inhibitors within the past 3 years
  • Respiratory failure requiring mechanical ventilation
Sex
Female & Male
Age
18+ years

Study Details

Medical Condition
  • Thrombotic Microangiopathy
Study Drug
  • Biological: Ravulizumab
Date
Jun 2021 - Dec 2022
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 18+ years years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • 18 years of age or older
  • Body weight ≥ 30 kilograms
  • 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
  • TMA associated with a trigger (autoimmune disease, infection, solid organ transplant, drugs, and malignant hypertension)
  • 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
  • Any known gene mutation that causes atypical hemolytic uremic syndrome (aHUS)
  • Postpartum aHUS
  • Known chronic kidney disease
  • TMA due to hematopoietic stem cell transplantation ≤ 12 months of Screening
  • Primary and secondary glomerular diseases other than lupus
  • Diagnosis of primary antiphospholipid antibody syndrome
  • Shiga toxin-producing Escherichia coli infections including but not limited to Shiga toxin-related hemolytic uremic syndrome
  • Known familial or acquired 'a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13' (ADAMTS13) deficiency (activity \< 5%)
  • Positive direct Coombs test which in the judgement of the Investigator is indicative of a clinically significant immune-mediated hemolysis not due to TMA
  • Clinical diagnosis of disseminated intravascular coagulation (DIC) in the judgement of the Investigator
  • Presence of sepsis requiring vasopressors within 7 days prior to or during Screening
  • Presence of monoclonal gammopathy including but not limited to multiple myeloma
  • Known bone marrow insufficiency or failure evidenced by cytopenias
  • Unresolved N. meningitidis infection
  • 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
  • Use of any complement inhibitors within the past 3 years
  • Respiratory failure requiring mechanical ventilation

Protocol 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.

Trial Locations

Location
Status
Location
Research Site
Tucson, Arizona, United States, 85724
Status
N/A
Location
Research Site
Orange, California, United States, 92868
Status
N/A
Location
Research Site
Washington D.C., District of Columbia, United States, 20007
Status
N/A
Location
Research Site
Gainesville, Florida, United States, 32610
Status
N/A
Location
Research Site
Lexington, Kentucky, United States, 40536
Status
N/A
Location
Research Site
Louisville, Kentucky, United States, 40202
Status
N/A
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