Avacostar - (PASS) (Avacostar)

Avacostar - A Post Authorization Safety Study (PASS) to Evaluate the Incidence of Safety Events of Interest in Patients Treated With Avacopan for ANCA-associated Vasculitis (AAV)

The Avacostar PASS is a non-interventional, multi-national, prospective cohort study that will collect data from 2 cohorts of patients: those treated with avacopan for active severe AAV, and a second cohort treated with a cyclophosphamide or rituximab-based induction regimen without avacopan for active severe AAV. The overall study duration is anticipated to be up to 7 years, including a recruitment period of approximately 3 years.

Study Overview

• Status: Recruiting
• Conditions: ANCA-associated Vasculitis

Detailed Description

The Avacostar PASS is a non-interventional, multi-national, prospective cohort study that will collect data from 2 cohorts of patients: those treated with avacopan for active severe AAV, and a second cohort treated with a cyclophosphamide or rituximab-based induction regimen without avacopan for active severe AAV. The overall study duration is anticipated to be up to 7 years, including a recruitment period of approximately 3 years. Enrolled patients will be followed until the last patient last visit (LPLV) milestone, which will be 4 years after the last participant is enrolled.

Germany and the United Kingdom (UK) have been selected for the study. Additional countries may be considered according to availability of avacopan and suitability for the study. Patients will be enrolled prospectively, but up to 6 months of data may be collected retrospectively if necessary. Baseline visit is defined as the day that induction treatment (avacopan or non-avacopan standard of care (SoC) cyclophosphamide or rituximab) is started for active severe AAV. Patients who started avacopan/SoC induction therapy for active severe AAV within 6 months of the enrolment visit and fulfil eligibility criteria may be enrolled in the PASS. Individual participant follow-up data will be collected periodically at routine clinic visits until the LPLV, which will be 4 years after the last participant is enrolled.

The primary objective of the study is:

To evaluate the incidence of defined Medical Events of Special Interest (MESIs) in patients with AAV commencing avacopan.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Avacostar Study Team; Phone Number: +41 58 851 80 00; Email: clinicaltrials@cslbehring.com

Study Locations

• Germany
  • Berlin, Germany
    • Recruiting
    • Charité University Medicine
  • Cologne, Germany
    • Not yet recruiting
    • University Hospital of Cologne
  • Dresden, Germany
    • Not yet recruiting
    • Municipal Hospital Dresden
  • Essen, Germany
    • Not yet recruiting
    • University Hospital Essen
  • Freiburg, Germany
    • Recruiting
    • University Hospital Freiburg
  • Göttingen, Germany
    • Recruiting
    • University Medical Center Göttingen
  • Hamburg, Germany
    • Not yet recruiting
    • University Hospital Eppendorf
  • Hannover, Germany
    • Recruiting
    • KRH Klinikum Siloah
  • Herne, Germany
    • Not yet recruiting
    • Rheumazentrum Ruhrgebiet
  • Munich, Germany
    • Not yet recruiting
    • LMU
  • Plochingen, Germany
    • Recruiting
    • Medius Kliniken
  • Sendenhorst, Germany
    • Not yet recruiting
    • St. Josef-Stift Sendenhorst
• United Kingdom
  • Birmingham, United Kingdom
    • Recruiting
    • UHB NHS Foundation Trust
  • Bristol, United Kingdom
    • Recruiting
    • North Bristol NHS Trust
  • Cambridge, United Kingdom
    • Recruiting
    • Addenbrookes Hospital
  • Canterbury, United Kingdom
    • Recruiting
    • East Kent Hospitals University NHS FT
  • Cardiff, United Kingdom
    • Recruiting
    • Cardiff and Vale UHB
  • Carshalton, United Kingdom
    • Recruiting
    • Epsom & St. Helier NHS Trust
  • Coventry, United Kingdom
    • Recruiting
    • University Hospitals Coventry and Warwickshire
  • Exeter, United Kingdom
    • Recruiting
    • Royal Devon University Healthcare NHS Foundation Trust
  • Glasgow, United Kingdom
    • Recruiting
    • NHS Greater Glasgow & Clyde
  • Leicester, United Kingdom
    • Recruiting
    • University Hospitals Of Leicester Nhs Trust
  • London, United Kingdom
    • Recruiting
    • Hammersmith Hospital, Imperial College Healthcare NHS Trust
  • London, United Kingdom
    • Recruiting
    • Barts Health
  • London, United Kingdom
    • Not yet recruiting
    • Royal Free
  • London, United Kingdom
    • Not yet recruiting
    • St Thomas' Hospital
  • Manchester, United Kingdom
    • Not yet recruiting
    • Manchester University NHS Foundation Trust
  • Nottingham, United Kingdom
    • Recruiting
    • Nottingham University Hospitals Nhs Trust
  • Oxford, United Kingdom
    • Recruiting
    • Rheumatology Department, Oxford University Hospitals NHS Foundation Trust
  • Portsmouth, United Kingdom
    • Not yet recruiting
    • Portsmouth Hospitals University NHS Trust
  • Reading, United Kingdom
    • Recruiting
    • Royal Berkshire NHS foundation trust
  • Salford, United Kingdom
    • Recruiting
    • Northern Care Alliance
  • Swansea, United Kingdom
    • Recruiting
    • Swansea Bay University LHB
  • York, United Kingdom
    • Recruiting
    • York & Scarborough Teaching Hospitals NHS FT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The Avacostar PASS is a non-interventional, multi-national, prospective cohort study that will collect data from 2 cohorts of patients: those treated with avacopan for active severe AAV, and a second cohort treated with a cyclophosphamide or rituximab-based induction regimen without avacopan for active severe AAV.

Description

Inclusion Criteria:

• Diagnosis of AAV (MPA or GPA), as determined by the Investigator according to their usual practice.
• Active, severe AAV at the time of commencing avacopan or non-avacopan SoC induction therapy, in the opinion of the Investigator.
• Age ≥18 years of either sex.
• Has provided written informed consent.
• Has commenced within the previous 6 months, or is planned to commence avacopan, cyclophosphamide or rituximab for the treatment of severe, active AAV outside of an interventional clinical study.

Exclusion Criteria:

• Concurrent participation in an interventional study, unless prospectively discussed and agreed with the Medical Monitor.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Treated with avacopan for active AAV; The study will enrol approximately 250 adult patients diagnosed with AAV (MPA or GPA) treated with avacopan for active severe AAV.
Treated with a cyclophosphamide or rituximab-based induction regimen without avacopan for active AAV; The study will enrol approximately 250 adult patients diagnosed with AAV (MPA or GPA) treated with a cyclophosphamide or rituximab-based induction regimen without avacopan for active severe AAV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the incidence of defined MESIs	To evaluate the incidence of defined MESIs in patients with AAV commencing avacopan. MESIs include liver injury, cardiac safety, serious infection, and malignancy.	up to 7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rates of AE in the avacopan and non-avacopan groups		up to 7 years
AEs leading to discontinuation of therapy in the avacopan group		up to 7 years
Incidence of SAEs in the avacopan and non-avacopan groups		up to 7 years
Incidence of ADRs in the avacopan group		up to 7 years
Incidence of SADRs in the avacopan group		up to 7 years
Change in eGFR over time in the avacopan and non-avacopan groups		up to 7 years
Change in IgG over time in the avacopan and non-avacopan groups		up to 7 years
Change in CPK over time in the avacopan and non-avacopan groups		up to 7 years
Change in ALT over time in the avacopan and non-avacopan groups		up to 7 years
Change in AST over time in the avacopan and non-avacopan groups		up to 7 years
Change in billirubin over time in the avacopan and non-avacopan groups		up to 7 years
Change in WBC over time in the avacopan and non-avacopan groups		up to 7 years
Change Albumin over time in the avacopan and non-avacopan groups		up to 7 years
Time to first flare over time in the avacopan and non-avacopan groups	A flare is defined in the BVAS as a score of more than 0. No flare is defined as a BVAS score equal to 0	up to 7 years
Change in VDI scores over time in the avacopan and non-avacopan groups		up to 7 years
Incidence of MESIs in the non-avacopan group		up to 7 years
Incidence rates of SAEs and MESIs in the avacopan group compared to the non-avacopan group,		up to 7 years
Incidence rates of MESIs in the avacopan group compared to the non-avacopan group,		up to 7 years
Use of concomitant immunosuppression over time and cumulative by treatment group,		up to 7 years
Duration of GC-free periods		up to 7 years
Proportion of GC-free patients over time by treatment group.		up to 7 years
Duration of treatment with avacopan by reason for treatment discontinuation.		up to 7 years

Collaborators and Investigators

• Sponsor: Vifor Fresenius Medical Care Renal Pharma

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2023
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: June 1, 2023
• First Submitted That Met QC Criteria: June 1, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: anti-neutrophil cytoplasmic antibody (ANCA)-AAV
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vascular; Systemic Vasculitis; Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Other Study ID Numbers: CS-AVA-2022-0016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• product manufactured in and exported from the U.S.: Yes