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Atypical Hemolytic Uremic SyndromePhase 2ACCESSNCT02464891

Complement Inhibition in aHUS Dialysis Patients

A Phase 2 study testing CCX168 in people with Atypical Hemolytic Uremic Syndrome, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Atypical Hemolytic Uremic Syndrome
What is being tested?
CCX168
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteItaly
Study dates
4 Jun 2015to 13 Jul 2017
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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);
Show all 12Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • 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

Other trials in Italy

About this study

Official 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

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.

Read the detailed description

Inherited defects that determine uncontrolled activation of the alternative complement pathway have been well documented in atypical Hemolytic Uremic Syndrome (aHUS) patients. Research in recent years has identified more than 120 different mutations, accounting for around 40%-60% of cases, in the genes encoding complement factor H (CFH), membrane cofactor protein (MCP), complement factor I (CFI), C3, complement factor B (CFB), and thrombomodulin (THBD). A therapeutic approach could be the administration of molecules that pharmacologically target complement activation, which is the primary common pathogenic mechanism in all genetic forms of aHUS. Eculizumab has been successfully used as prophylaxis of aHUS recurrences in subjects with plasma dependent or plasma resistant disease or in renal transplant recipients at high risk of recurrence due to CFH, CFI, or C3 complement gene mutations. However the drug must be administered chronically and drug spacing or discontinuance was associated with disease recurrence in the graft. The C5aR receptor antagonist CCX168 could present an appealing alternative to eculizumab for post-transplant prophylaxis of aHUS recurrences since it is orally administrable with lower cost of goods. In addition, CCX168 is theoretically associated with lower risk of infections than eculizumab since the former does not target C5b and leaves the terminal complement pathway intact.

Being tested
CCX168
Keywords
Atypical Hemolytic Uremic Syndrome, CCX168, dialysis, C5aR antagonist
Medical subject headings
Atypical Hemolytic Uremic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CCX168Drug

Study groups in NCT02464891
Study groupRoleWhat they receive
CCX168ExperimentalStudy medication will be administered as hard gelatin capsules containing 10 mg CCX168. Patients will take 30 mg CCX168, given as 3 x 10 mg capsule, twice daily for 15 days.
Receives: Drug: CCX168

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ex vivo thrombogenesis.

    Measured: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).

Secondary outcomes (13)

  1. Complement component 3 serum levels.

    Measured: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).

  2. Complement component 4 serum levels.

    Measured: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).

  3. Complement component 5 serum levels.

    Measured: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).

  4. Complement Factor H.

    Measured: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).

  5. Complement component 5a.

    Measured: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).

  6. Soluble thrombomodulin.

    Measured: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).

  7. Fibrin split products..

    Measured: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).

  8. Ex vivo C5b-9 deposition on microvascular endothelial cells

    Measured: At baseline.

  9. Changes in pre-dialysis and intradialytic blood pressure.

    Measured: The participants will be followed for the duration of the study up to 21 days.

  10. Changes in heart rate.

    Measured: The participants will be followed for the duration of the study up to 21 days.

  11. Safety and tolerability parameters including serious and non serious events

    Measured: The participants will be followed for the duration of the study up to 21 days.

  12. Patient health-related quality of life as measured by administration of EQ-5D-5L questionnaire.

    Measured: Changes from baseline at 14 and 21 day.

  13. 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

    Measured: Changes from Baseline at 4,9,11 and 15 day.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2015 (estimated)
  2. Study start4 Jun 2015
  3. Primary completion13 Jul 2017
  4. Study completion13 Jul 2017

Why it stopped: The study had accomplished its goal with the 6 patients who have been enrolled.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02464891
Sponsor's protocol ID
CL006_168
Other IDs
2014-004261-24, 2014
Acronym
ACCESS
Status last verified
Nov 2017
First submitted
26 May 2015
Last updated
14 Nov 2017
Results posted
No
Data monitoring committee
No

Publications

  • Aiello S, Gastoldi S, Galbusera M, Ruggenenti P, Portalupi V, Rota S, Rubis N, Liguori L, Conti S, Tironi M, Gamba S, Santarsiero D, Benigni A, Remuzzi G, Noris M. C5a and C5aR1 are key drivers of microvascular platelet aggregation in clinical entities spanning from aHUS to COVID-19. Blood Adv. 2022 Jan 8;6(3):866-881. doi: 10.1182/bloodadvances.2021005246.

    PubMed 34852172

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CCX168 in people with Atypical Hemolytic Uremic Syndrome, run by Mario Negri Institute for Pharmacological Research at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study had accomplished its goal with the 6 patients who have been enrolled.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ex vivo thrombogenesis. (time frame: Changes from baseline at day 2,14 (during CCX168 treatment), 16 and 21 (after treatment withdrawal).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02464891, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2017.

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