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Zibotentan Better Renal Scleroderma Outcome Study (ZEBRA)

Primary Purpose

Scleroderma, Scleroderma Renal Crisis, Chronic Kidney Disease

Status

Completed

Phase

Phase 2

Locations

United Kingdom

Study Type

Interventional

Intervention

Zibotentan

About this trial

This is an interventional treatment trial for Scleroderma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Previous use of an endothelin receptor antagonist within 3 months of the study start
Significant abnormalities in liver function testing (ALT, ALP, Bilirubin) more than three times upper limit of normal)
Patients with body weight <40kg.
Patients with conditions which prevent compliance with the protocol or failure to adhere to therapy.
Patients with any other life threatening condition.
Patients with known hypersensitivity to Zibotentan or its excipients
Previous history of epilepsy or other CNS AEs, neurologic symptoms or signs consistent with acute or evolving spinal cord compression, and CNS metastases
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.
History of chronic alcohol or drug abuse or any condition associated with poor compliance as judged by the investigator
Patients receiving cyclosporin A within 1 week of screening or expecting to receive this agent during the study.
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.
Active malignancy or neoplastic disease in the previous 12 months
Women who rely on oestrogencontaining contraceptives (due to potential drug interaction with Zibotentan).
Females who are pregnant or breastfeeding.

Sites / Locations

Royal Free London NHS Foundation Trust

Outcomes

Primary Outcome Measures

sVCAM 1 soluble Vascular Cell Adhesion Molecule

sVCAM1 is a biomarker of renal involvement in scleroderma

Secondary Outcome Measures

Full Information

NCT ID

NCT02047708

First Posted

January 22, 2014

Last Updated

October 30, 2017

Sponsor

University College, London

Collaborators

Medical Research Council

1. Study Identification

Unique Protocol Identification Number

NCT02047708

Brief Title

Zibotentan Better Renal Scleroderma Outcome Study

Acronym

ZEBRA

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Completed

Study Start Date

October 2014 (undefined)

Primary Completion Date

October 2017 (Actual)

Study Completion Date

October 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University College, London

Collaborators

Medical Research Council

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Scleroderma, Scleroderma Renal Crisis, Chronic Kidney Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Zibotentan

Other Intervention Name(s)

ZD4054

Intervention Description

Selective endothelin-A antagonist

Primary Outcome Measure Information:

Title

sVCAM 1 soluble Vascular Cell Adhesion Molecule

Description

sVCAM1 is a biomarker of renal involvement in scleroderma

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adults with scleroderma and: CKD 2/3 (ZEBRA 1) Renal crisis not on dialysis (ZEBRA 2A) Renal crisis on dialysis (ZEBRA 2B) Exclusion Criteria: Previous use of an endothelin receptor antagonist within 3 months of the study start Significant abnormalities in liver function testing (ALT, ALP, Bilirubin) more than three times upper limit of normal) Patients with body weight <40kg. Patients with conditions which prevent compliance with the protocol or failure to adhere to therapy. Patients with any other life threatening condition. Patients with known hypersensitivity to Zibotentan or its excipients Previous history of epilepsy or other CNS AEs, neurologic symptoms or signs consistent with acute or evolving spinal cord compression, and CNS metastases 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. History of chronic alcohol or drug abuse or any condition associated with poor compliance as judged by the investigator Patients receiving cyclosporin A within 1 week of screening or expecting to receive this agent during the study. 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. Active malignancy or neoplastic disease in the previous 12 months Women who rely on oestrogencontaining contraceptives (due to potential drug interaction with Zibotentan). Females who are pregnant or breastfeeding.

Facility Information:

Facility Name

Royal Free London NHS Foundation Trust

City

London

ZIP/Postal Code

NW32QG

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

35650639

Citation

Stern EP, Host LV, Wanjiku I, Escott KJ, Gilmour PS, Ochiel R, Unwin R, Burns A, Ong VH, Cadiou H, O'Keeffe AG, Denton CP. Zibotentan in systemic sclerosis-associated chronic kidney disease: a phase II randomised placebo-controlled trial. Arthritis Res Ther. 2022 Jun 1;24(1):130. doi: 10.1186/s13075-022-02818-6.

Results Reference

derived

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Zibotentan Better Renal Scleroderma Outcome Study

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