Eculizumab to Cemdisiran Switch in aHUS

Sponsor
Mario Negri Institute for Pharmacological Research
Study ID
NCT03999840
Phase
PHASE2
Status
Withdrawn

Conditions

  • Atypical Hemolytic Uremic Syndrome

Eligibility Criteria

Sex
ALL
Age
12 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • cemdisiran — DRUG
    Cemdisiran has been designed to reduce the level of C5 mRNA in the liver, thereby reducing levels of circulating C5 protein, inhibiting terminal complement pathway activity, and preventing formation and deposition of the MAC (C5-b9) on endothelial cells in the kidney.
  • Placebos — DRUG
    The control drug for this study will be a placebo (sodium chloride 0.9% w/v for SC administration). Placebo will be prepared and labelled identically to cemdisiran.

Study Details

Atypical Hemolytic Uremic Syndrome (aHUS) is a rare, lifethreatening, chronic disease of complement-mediated thrombotic microangiopathy (TMA) characterized by acute onset of renal impairment, thrombocytopenia, and microangiopathic hemolytic anemia. The estimated incidence of aHUS is approximately 0.5 per million per year. aHUS affects both adults and children, but is observed primarily in children and young adults. Atypical HUS commonly develops due to dysregulation of the alternative complement pathway and can be sporadic (80%) or familial(20%). The clinical course of aHUS is often unpredictable and can be dependent upon the specific genetic abnormality present within the complement system, if any, and/or triggering events associated with complement activation or inflammation, including autoimmune disease, transplant, pregnancy, infection, metabolic conditions, and drug use. In patients with dysregulated complement activity, such as those with complement mutations commonly observed in aHUS, the kidney vasculature is often the site of thrombosis stemming from endothelial injury. Cemdisiran has been designed to reduce the level of C5 mRNA in the liver, thereby reducing levels of circulating C5 protein, inhibiting terminal complement pathway activity, and preventing formation and deposition of the MAC (C5-b9) on endothelial cells in the kidney. As a result, complement-mediated endothelial cell damage in patients with aHUS and subsequent progression to End Stage Renal Disease (ESRD) may be reduced.

Key Dates

Start date
Jan 31, 2021
Status verified
Mar 2021
Primary completion
Jan 31, 2024
Completion
Mar 31, 2024

Study Design

Enrollment
0 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: IMP
    Cemdisiran (600 mg) or placebo will be administered subcutaneously every four weeks up to week 32 (end of the Core Study).
  • Placebo Comparator: Placebo
    Cemdisiran (600 mg) or placebo will be administered subcutaneously every four weeks up to week 32 (end of the Core Study).

Primary Outcome Measure

Ex vivo complement activation on the surface of cultured microvascular endothelial cells exposed to patient sera [ Time Frame: Changes from baseline and 16,32,44,60, 84 and 108 weeks after randomization. ]

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