Atypical Hemolytic Uremic Syndrome Clinical Trial
— ACCESSOfficial title:
An Open-label Phase 2 Study to Assess the Effect of C5aR Antagonist Therapy by CCX168 Oral Administration on ex Vivo Thrombus Formation and Disease Activity in ESRD Patients With Atypical Hemolytic Uremic Syndrome
Verified date | November 2017 |
Source | Mario Negri Institute for Pharmacological Research |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This study evaluates the effect of CCX168, a C5aR Antagonist, Oral Administration on Ex Vivo Thrombus Formation and Disease Activity in ten patients with diagnosis of Atypical Hemolytic Uremic Syndrome with or without genetic abnormalities in the complement system or thrombomodulin, on stable chronic extracorporeal or peritoneal dialysis therapy since at least 6 months.
Status | Terminated |
Enrollment | 6 |
Est. completion date | July 13, 2017 |
Est. primary completion date | July 13, 2017 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Age >18 years; - Diagnosis of aHUS with or without identified genetic abnormalities in the complement system or thrombomodulin; - Stable chronic extracorporeal or peritoneal dialysis therapy since at least 6 months; - Written informed consent. Exclusion Criteria: - Women of childbearing potential or women who are breastfeeding; - Shiga toxin-associated HUS or secondary forms of thrombotic microangiopathy; - ADAMTS13 activity <10 % or circulating anti ADAMTS13 autoantibodies consistent with the diagnosis of thrombotic thrombocytopenic purpura; - Need for specific intervention with plasma therapy and/or complement inhibitors as deemed clinically appropriate; - Plasma therapy or treatment with complement inhibitors or antiplatelet and antithrombotic agents over the last two weeks; - Liver function impairment (serum liver enzymes or bilirubin levels >3 x upper limit of normal); - Neutrophil count < 2000/µL or lymphocyte count < 1000/µL; - Infection requiring antibiotic treatment within the previous 4 weeks prior to screening; - Participated in any clinical study of an investigational product within 30 days prior to screening or within 5 half-lives after taking the last dose; - History or presence of any medical condition or disease which, in the opinion of the Investigator may place the subject at unacceptable risk for study participation; - Inability to understand the potential risks and benefits of the study; - Legal incapacity. |
Country | Name | City | State |
---|---|---|---|
Italy | A.O. Papa Giovanni XXIII - U.O. Nefrologia e Dialisi/IRCCS IRFMN - Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò | Bergamo |
Lead Sponsor | Collaborator |
---|---|
Mario Negri Institute for Pharmacological Research | ChemoCentryx |
Italy,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Ex vivo thrombogenesis. | Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal). | ||
Secondary | Complement component 3 serum levels. | Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal). | ||
Secondary | Complement component 4 serum levels. | Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal). | ||
Secondary | Complement component 5 serum levels. | Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal). | ||
Secondary | Complement Factor H. | Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal). | ||
Secondary | Complement component 5a. | Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal). | ||
Secondary | Soluble thrombomodulin. | Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal). | ||
Secondary | Fibrin split products.. | Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal). | ||
Secondary | Ex vivo C5b-9 deposition on microvascular endothelial cells | At baseline. | ||
Secondary | Changes in pre-dialysis and intradialytic blood pressure. | The participants will be followed for the duration of the study up to 21 days. | ||
Secondary | Changes in heart rate. | The participants will be followed for the duration of the study up to 21 days. | ||
Secondary | Safety and tolerability parameters including serious and non serious events | The participants will be followed for the duration of the study up to 21 days. | ||
Secondary | Patient health-related quality of life as measured by administration of EQ-5D-5L questionnaire. | Changes from baseline at 14 and 21 day. | ||
Secondary | Characterization of CCX168 pharmacokinetic profile after oral administration by determining by maximum plasma concentration, time of maximum plasma concentration and area under the plasma concentration-time curve from time 0 to hour 6 | Changes from Baseline at 4,9,11 and 15 day. |
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