Zibotentan Better Renal Scleroderma Outcome Study (ZEBRA)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2014 by University College, London
Sponsor:
Collaborator:
Medical Research Council
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT02047708
First received: January 22, 2014
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

Many patients with scleroderma have damage to their kidneys caused by the disease. There is limited evidence for treatments to prevent this damage or stop it progressing. Blocking a substance in the blood called endothelin has helped treat some aspects of scleroderma. The purpose of this study is to see how effective a new endothelin blocker called Zibotentan is in treating patients who have scleroderma and have gone on to develop reduced kidney function as a complication. It will be given in addition to the accepted treatments used for scleroderma. There will be three parts to this study each for a different group of patients:

  • ZEBRA 1 for patients with mild or moderate kidney disease caused by scleroderma
  • ZEBRA 2A for patients with a more severe, acute form of kidney disease caused by scleroderma (scleroderma renal crisis) who do not require dialysis
  • ZEBRA 2B for patients who have had scleroderma renal crisis and are on dialysis

Condition Intervention Phase
Scleroderma
Scleroderma Renal Crisis
Chronic Kidney Disease
Drug: Zibotentan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Single Centre, Randomised, Placebo-controlled, 3-part Trial to Assess the Safety, Tolerability and Efficacy of Zibotentan in Patients With Renal Disease Secondary to Scleroderma

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • sVCAM 1 ​soluble Vascular Cell Adhesion Molecule [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    sVCAM1 is a biomarker of renal involvement in scleroderma


Estimated Enrollment: 72
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Zibotentan
    Selective endothelin-A antagonist
    Other Name: ZD4054
Detailed Description:

This is a 3-part study (Zebra 1, 2A and 2B) that will explore safety and therapeutic potential of Zibotentan in acute and chronic renal complications of Scleroderma. Trial duration will be 52 weeks for Zebra 1 and 2A (1 or 2 weeks for ZEBRA 2B with 1 year follow up data). Scleroderma (Systemic sclerosis) is a multisystem rheumatic disease that results in vascular damage and fibrosis of target organs.This project will focus specifically on the evaluation and treatment of renal disease in scleroderma.

Renal involvement in Scleroderma occurs with a variety of different pathologies; hypertensive scleroderma renal crisis (SRC) being the most dramatic manifestation but milder forms of chronic renal disease are frequent and represent an important clinical feature.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults with scleroderma and:
  2. CKD 2/3 (ZEBRA 1)
  3. Renal crisis not on dialysis (ZEBRA 2A)
  4. Renal crisis on dialysis (ZEBRA 2B)

Exclusion Criteria:

  1. Previous use of an endothelin receptor antagonist within 3 months of the study start
  2. Significant abnormalities in liver function testing (ALT, ALP, Bilirubin) more than three times upper limit of normal)
  3. Patients with body weight <40kg.
  4. Patients with conditions which prevent compliance with the protocol or failure to adhere to therapy.
  5. Patients with any other life threatening condition.
  6. Patients with known hypersensitivity to Zibotentan or its excipients
  7. Previous history of epilepsy or other CNS AEs, neurologic symptoms or signs consistent with acute or evolving spinal cord compression, and CNS metastases
  8. Patients with a baseline left ventricular ejection fraction < 40% (prior to any scleroderma renal crisis), patients with acute myocardial infarction within six months or patients who are judged by the trial clinician to be at unacceptable risk from cardiac complications.
  9. History of chronic alcohol or drug abuse or any condition associated with poor compliance as judged by the investigator
  10. Patients receiving cyclosporin A within 1 week of screening or expecting to receive this agent during the study.
  11. Patients who have received an investigational agent in the month prior to screening. These patients may be eligible if after a month of washout period, they are still within 112 months of the onset of the Scleroderma renal crisis.
  12. Active malignancy or neoplastic disease in the previous 12 months
  13. Women who rely on oestrogencontaining contraceptives (due to potential drug interaction with Zibotentan).
  14. Females who are pregnant or breastfeeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02047708

Locations
United Kingdom
Royal Free London NHS Foundation Trust Not yet recruiting
London, United Kingdom, NW32QG
Contact: Edward Stern, MBBS       e.stern@ucl.ac.uk   
Principal Investigator: Christopher Denton, PhD         
Sponsors and Collaborators
University College, London
Medical Research Council
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT02047708     History of Changes
Other Study ID Numbers: 2013-003200-39
Study First Received: January 22, 2014
Last Updated: January 27, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Urologic Diseases
Renal Insufficiency
Connective Tissue Diseases
Skin Diseases

ClinicalTrials.gov processed this record on September 22, 2014