NCT02047708

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
27

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Oct 2014

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 22, 2014

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 28, 2014

Completed
8 months until next milestone

Study Start

First participant enrolled

October 1, 2014

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2017

Completed
Last Updated

October 31, 2017

Status Verified

October 1, 2017

Enrollment Period

3 years

First QC Date

January 22, 2014

Last Update Submit

October 30, 2017

Conditions

SclerodermaScleroderma Renal CrisisChronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

  • sVCAM 1 soluble Vascular Cell Adhesion Molecule

    sVCAM1 is a biomarker of renal involvement in scleroderma

    12 months

Interventions

ZibotentanDRUG

Selective endothelin-A antagonist

Also known as: ZD4054

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Royal Free London NHS Foundation Trust

London, NW32QG, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 35650639DERIVED

MeSH Terms

Conditions

Scleroderma, DiffuseRenal Insufficiency, Chronic

Interventions

ZD4054

Condition Hierarchy (Ancestors)

Scleroderma, SystemicConnective Tissue DiseasesSkin and Connective Tissue DiseasesSkin DiseasesRenal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 22, 2014

First Posted

January 28, 2014

Study Start

October 1, 2014

Primary Completion

October 1, 2017

Study Completion

October 1, 2017

Last Updated

October 31, 2017

Record last verified: 2017-10

Locations

GB(1)