Complement Inhibition in aHUS Dialysis Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT02464891
• Date of registration: 26/05/2015
• Prospective Registration: Yes
• Primary sponsor: Mario Negri Institute for Pharmacological Research
• Public title: Complement Inhibition in aHUS Dialysis Patients ACCESS
• Scientific 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
• Date of first enrolment: June 4, 2015
• Target sample size: 6
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02464891
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Italy

Contacts

• Name: Giuseppe Remuzzi, MD
• Affiliation: IRCCS - Mario Negri Institute for Pharmacological Research/A.O. Papa Giovanni XXIII- BG

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Atypical Hemolytic Uremic Syndrome

Intervention(s)

Drug: CCX168

Primary Outcome(s)

Ex vivo thrombogenesis. [Time Frame: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).]

Secondary Outcome(s)

Complement Factor H. [Time Frame: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).]

Changes in heart rate. [Time Frame: The participants will be followed for the duration of the study up to 21 days.]

Complement component 5a. [Time Frame: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).]

Patient health-related quality of life as measured by administration of EQ-5D-5L questionnaire. [Time Frame: Changes from baseline at 14 and 21 day.]

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 [Time Frame: Changes from Baseline at 4,9,11 and 15 day.]

Ex vivo C5b-9 deposition on microvascular endothelial cells [Time Frame: At baseline.]

Safety and tolerability parameters including serious and non serious events [Time Frame: The participants will be followed for the duration of the study up to 21 days.]

Changes in pre-dialysis and intradialytic blood pressure. [Time Frame: The participants will be followed for the duration of the study up to 21 days.]

Complement component 3 serum levels. [Time Frame: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).]

Complement component 4 serum levels. [Time Frame: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).]

Complement component 5 serum levels. [Time Frame: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).]

Soluble thrombomodulin. [Time Frame: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).]

Fibrin split products.. [Time Frame: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).]

Secondary ID(s)

2014-004261-24

CL006_168

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

ChemoCentryx