ETA and AT1 Antagonism in ANCA-vasculitis (SPARVASC)

NCT05630612 | Active Not Recruiting Phase 2

• 1 other identifier: AC22084
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

ANCA-associated vasculitis is an autoimmune disease that causes damage to blood vessels. This leads to organ damage with the number of organs affected and the severity of damage varying significantly between patients. Vasculitis patients also have a very high risk of heart attacks and strokes, called cardiovascular disease. A chemical called 'endothelin', produced by the blood vessels, causes vessels to stiffen and raises blood pressure and this associates with cardiovascular risk. The investigators have previously shown that by blocking the effects of endothelin you reduce vessel stiffness, lower blood pressure and improve vessel function. However, these studies only blocked endothelin for a few hours. Now, the investigators would like to see if it is possible to maintain these benefits by blocking endothelin for longer. Sparsentan is a tablet that blocks endothelin and lowers blood pressure. The investigators plan to give sparsentan to patients with vasculitis for 6 weeks. To determine if any beneficial effects of sparsentan are due to blood pressure lowering the investigators will give another group of vasculitis patients a tablet called irbesartan which lowers blood pressure but does not block endothelin. The investigators will compare the results between the two groups.

Conditions

ANCA Associated Vasculitis; Cardiovascular Diseases; Kidney Diseases

Outcome Measures

Primary Outcomes (1)

• Forearm blood flow

  Change from baseline to week 6 in acetylcholine-mediated forearm blood flow vasodilatation

  Comparing baseline to after 6 weeks of intervention.

Secondary Outcomes (5)

• Fibrinolytic capacity

  Comparing baseline to after 6 weeks of intervention.

• Blood pressure

  Comparing baseline to after 3 and 6 weeks of treatment.

• Arterial stiffness

  Comparing baseline to after 3 and 6 weeks of treatment.

• Systemic haemodynamics

  Comparing baseline to after 3 and 6 weeks of treatment.

• Proteinuria

  Comparing baseline to after 3 and 6 weeks of treatment.

Other Outcomes (3)

• Optical Coherence Tomography (OCT)

  Comparing baseline to after 3 and 6 weeks of treatment.

• Fluorescence-activated cell sorting

  Comparing baseline to after 6 weeks of treatment.

• Endothelin-1 clearance

  Comparing baseline to after 6 weeks of treatment.

Study Arms (2)

Sparsentan

EXPERIMENTAL

20 participants with ANCA-associated vasculitis in long-term disease remission. Participants will undergo a forearm blood flow study where forearm vasodilatation will be assessed in response to acetylcholine (7.5, 15 and 30ug/min) and sodium nitroprusside (1, 2 and 4ug/min). Participants will also receive bradykinin (100, 300 and 1000pmol/min) in order to assess tPA release to measure fibrinolytic capacity. Participants will also have 24h blood pressure assessed as well as measurements of arterial stiffness, systemic haemodynamics and measures of urinary protein. After these baseline measures have been obtained the subject will receive 6 weeks of sparsentan. Finally the subject will undergo the same investigations listed above and we will compare to see if measurements obtained differ after treatment.

Drug: Sparsentan

Irbesartan

ACTIVE COMPARATOR

20 participants with ANCA-associated vasculitis in long-term disease remission. Participants will undergo a forearm blood flow study where forearm vasodilatation will be assessed in response to acetylcholine (7.5, 15 and 30ug/min) and sodium nitroprusside (1, 2 and 4ug/min). Participants will also receive bradykinin (100, 300 and 1000pmol/min) in order to assess tPA release to measure fibrinolytic capacity. Participants will also have 24h blood pressure assessed as well as measurements of arterial stiffness, systemic haemodynamics and measures of urinary protein. After these baseline measures have been obtained the subject will receive 6 weeks of irbesartan. Finally the subject will undergo the same investigations listed above and we will compare to see if measurements obtained differ after treatment.

Drug: Sparsentan

Interventions

Sparsentan DRUG

6 weeks of treatment with sparsentan or irbesartan. This will be administered in a double-blind fashion.

Irbesartan; Sparsentan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• A diagnosis of ANCA-associated vasculitis that has been in remission for ≥6 months.
• The diagnosis of AAV will have been made in accordance with the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides criteria. Remission will be defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 for at least 2 months prior to the screening visit whilst taking prednisolone at daily dose ≤7.5mg, in conjunction with the treating clinician's assessment of clinically silent disease.
• eGFR ≥25ml/min/1.73m2 at screening.
• Women of childbearing potential, beginning at menarche, must agree to the use of one highly reliable method of contraception (ie, a failure rate of \<1% per year) for at least 30 days prior to the first dose of the study medication (ie, for hormonal contraception) or according to manufacturer's recommendation (ie, for an intrauterine device) until 30 days after the last dose of the study medication, and must have a negative pregnancy test at screening. Women of childbearing potential are defined as those who are fertile, following menarche and until becoming postmenopausal, unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as amenorrhea for more than 24 consecutive months without an alternative medical cause; women on hormone replacement therapy must have a documented plasma follicle-stimulating hormone level \>40 mIU/mL.

You may not qualify if:

• Age \<18 years
• Active vasculitis
• Liver disease
• Untreated hypertension (defined as systolic blood pressure \>160 bpm and diastolic blood pressure \>100 bpm)
• eGFR \<25ml/min/1.73m2
• Any organ transplant recipients
• Haemodialysis/peritoneal dialysis patients
• A requirement for any medications contraindicated whilst taking sparsentan
• Congestive heart failure
• Patients not medically fit to attend for study visits
• Patients without mental capacity or willingness to provide informed consent
• History of multiple and/or severe (clinical judgement as determined by the investigator) allergic reactions to drugs, including the study drug or food.
• Patients who are pregnant or breast feeding, or those who plan to become pregnant during the study
• Participation in another clinical trial for 28 days before or 90 days after the study period.

Sponsors & Collaborators

• University of Edinburgh: lead
• Travere Therapeutics, Inc.: collaborator

Study Sites (1)

Centre for Cardiovascular Science, Queen's Medical Research Institute, 47 Little France Crescent

Edinburgh, EH16 4TJ, United Kingdom

Location

Related Publications (1)

• Farrah TE, Melville V, Czopek A, Fok H, Bruce L, Mills NL, Bailey MA, Webb DJ, Dear JW, Dhaun N. Arterial stiffness, endothelial dysfunction and impaired fibrinolysis are pathogenic mechanisms contributing to cardiovascular risk in ANCA-associated vasculitis. Kidney Int. 2022 Nov;102(5):1115-1126. doi: 10.1016/j.kint.2022.07.026. Epub 2022 Aug 20.

  PMID: 35998848 BACKGROUND

MeSH Terms

Conditions

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Cardiovascular Diseases; Kidney Diseases

Interventions

sparsentan

Condition Hierarchy (Ancestors)

Systemic Vasculitis; Vasculitis; Vascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Neeraj Dhaun

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All investigators will be blinded as will the participants.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised, double blind, active control, parallel group study

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: November 29, 2022
• Study Start: December 8, 2022
• Primary Completion: July 18, 2024
• Study Completion (Estimated): September 1, 2027
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)