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PROPOSAL OF STUDY TO DETERMINE IF THE ORAL ADMINISTRATION OF CCX168 INHIBITS THE ACTIVITY 'COMPLEMENT AND THE FORMATION OF CLOTS IN PATIENTS WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME IN DIALYSIS

Phase 1
Conditions
Atypical Hemolytic Uremic Syndrome
MedDRA version: 20.0Level: LLTClassification code 10019515Term: Hemolytic uremic syndromeSystem Organ Class: 100000004851
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
Registration Number
EUCTR2014-004261-24-IT
Lead Sponsor
IRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
10
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.
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

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.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To evaluate whether in vivo CCX168 treatment dampens the ex vivo prothrombogenic properties of<br>serum from ten chronic dialysis patients with aHUS on cultured microvascular endothelial cells.;Secondary Objective: To evaluate the effects of in vivo CCX168 treatment on:<br>i. Biomarkers of complement and disease activity<br>ii. Clinical parameters including pre-dialysis and intradialytic<br>blood pressure and heart rate<br>iii. Safety and tolerability parameters<br>iv. Patient health-related quality of life<br>v. CCX168 pharmacokinetic (PK) profile.;Primary end point(s): Ex vivo thrombogenesis.;Timepoint(s) of evaluation of this end point: Day 0, 3, 14,16 and 21.
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): Patient health-related quality of life.;Timepoint(s) of evaluation of this end point: Day 0, 14 and 21.
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