Phase 3
N=331
A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis
ANCA-Associated Vasculitis
Bottom Line
View on ClinicalTrials.gov: NCT02994927 ↗Enrolled (actual)
331
Serious AEs
43.6%
Results posted
Sep 2022
Primary outcome: Primary: Percentage of Subjects Achieving Disease Remission at Week 26 — 70.1; 72.3 percentage of participants — p=< 0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Avacopan (Drug); Prednisone (Drug); Cyclophosphamide (Drug); Rituximab (Biological); Azathioprine (Drug)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- Amgen
- Primary completion
- Sep 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Subjects Achieving Disease Remission at Week 26 |
70.1; 72.3 | < 0.0001 sig |
| PRIMARY Percentage of Subjects Achieving Sustained Disease Remission at Week 52 |
54.9; 65.7 | < 0.0001 sig |
| SECONDARY Subject Incidence of Treatment-emergent SAEs, AEs, and Withdrawals Due to AEs |
161; 164; 2139; 1779; 74; 70 | — |
| SECONDARY Glucocorticoid-induced Toxicity as Measured by Change From Baseline Over the First 26 Weeks in the GTI |
36.6; 25.7; 56.6; 39.7; 23.2; 9.9 | — |
| SECONDARY Percentage of Participants With BVAS of 0 at Week 4, Regardless of Whether the Subjects Received Glucocorticoids During This Period of Time and Based on Assessment by the Blinded AC |
68.9; 62.7 | — |
| SECONDARY Change From Baseline Over 52 Weeks in Health-related Quality of Life as Measured by the Domains and Component Scores of the SF-36v2 and EQ-5D-5L VAS and Index |
1.344; 4.445; 2.626; 4.980; 1.88; 7.31 | — |
| SECONDARY Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving Remission at Week 26 in the Study |
12.2; 7.5 | — |
| SECONDARY Percentage of Subjects and Time to Experiencing a Relapse After Previously Achieving BVAS=0 at Any Time During the Treatment Period |
21.0; 10.1 | — |
| SECONDARY In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Change in eGFR From Baseline Over 52 Weeks |
2.9; 5.8; 4.1; 7.3 | — |
| SECONDARY In Subjects With Renal Disease and Albuminuria at Baseline (Based in the BVAS Renal Component), the Percent Change in UACR From Baseline Over 52 Weeks |
0; -40; -70; -63; -77; -74 | — |
| SECONDARY In Subjects With Renal Disease at Baseline (Based in the BVAS Renal Component), the Percent Change in Urinary MCP-1:Creatinine Ratio From Baseline Over 52 Weeks |
-64; -67; -71; -73 | — |
| SECONDARY Change in the VDI From Baseline Over 52 Weeks, Including the Week 26 and Week 52 Time Points |
0.97; 1.06; 1.15; 1.17 | — |
| SECONDARY Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (1/5) |
-5.69; -5.94; -5.54; -5.62; -5.10; -5.24 | — |
| SECONDARY Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (2/5) |
0.07; 0.07; 0.05; 0.07; -0.01; -0.00 | — |
| SECONDARY Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (3/5) |
0.226; 0.252; 0.244; 0.279 | — |
| SECONDARY Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (4/5) |
1.07; 1.10; 1.20; 1.27 | — |
| SECONDARY Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Hematology (5/5) |
2.6; 2.7; 3.0; 3.2 | — |
| SECONDARY Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (1/2) |
2.3; -6.1; -8.6; -10.7; -0.6; -3.9 | — |
| SECONDARY Change From Baseline and Shifts From Baseline in All Safety Laboratory Parameters - Serum Chemistry (2/2) |
-0.105; -0.195; -0.200; -0.244; -9.4; -11.0 | — |
| SECONDARY Change From Baseline in Vital Signs (1/5) |
-2.5; -2.6; -2.4; -1.0; 2.7; 0.5 | — |
| SECONDARY Change From Baseline in Vital Signs (2/5) |
2.2; 0.9; -1.3; -0.3 | — |
| SECONDARY Change From Baseline in Vital Signs (3/5) |
-0.03; -0.11; 0.04; -0.11 | — |
| SECONDARY Change From Baseline in Vital Signs (4/5) |
3.33; 1.93; 3.27; 2.59 | — |
| SECONDARY Change From Baseline in Vital Signs (5/5) |
1.13; 0.67; 1.12; 0.94 | — |
| SECONDARY Number of Subjects With Clinically Significant ECG Changes From Baseline |
8; 12 | — |
| SECONDARY Number of Subjects Where a Relationship Between Avacopan/Placebo, Glucocorticoid Use, Cyclophosphamide, Rituximab, and Azathioprine or Mycophenolate Use to an AE Was Determined by the Investigator |
103; 100; 131; 107; 30; 31 | — |
| SECONDARY Certain Safety Endpoints of Interest: Infections, Hepatic System Abnormalities, WBC Count Decreases, and Hypersensitivity |
124; 113; 25; 22; 10; 12 | — |
| SECONDARY Number of Subjects Experiencing a Relapse After Previously Achieving BVAS=0 During the Study |
33; 16 | — |
Summary
The primary objective is to evaluate the efficacy of CCX168 (avacopan) to induce and sustain remission in patients with active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), when used in combination with cyclophosphamide followed by azathioprine, or in combination with rituximab.
Eligibility Criteria
Inclusion Criteria
- Clinical diagnosis of granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis
- Male and female subjects, aged at least 18 years, with newly-diagnosed or relapsed associated vasculitis (AAV) where treatment with cyclophosphamide or rituximab is needed; where approved by Regulatory Agencies, adolescents (12-17 year old) may be enrolled
- Use of adequate contraception
- Positive test for anti-proteinase 3 (PR3) or anti-myeloperoxidase (MPO)
- At least 1 major item, or at least 3 non-major items, or at least the 2 renal items of proteinuria and hematuria on Birmingham Vasculitis Activity Score (BVAS)
- Estimated glomerular filtration rate ≥15 mL/minute/1.73 m^2 at screening
Exclusion Criteria
- Pregnant or breast-feeding
- Alveolar hemorrhage requiring pulmonary ventilation support at screening
- Any other known multi-system autoimmune disease
- Required dialysis or plasma exchange within 12 weeks prior to screening
- Have a kidney transplant
- Received cyclophosphamide within 12 weeks prior to screening; if on azathioprine, mycophenolate mofetil or methotrexate at the time of screening, these drugs must be withdrawn prior to receiving the cyclophosphamide or rituximab dose on Day 1
- Received intravenous glucocorticoids, >3000 mg methylprednisolone equivalent, within 4 weeks prior to screening
- Have been taking an oral daily dose of a glucocorticoid of more than 10 mg prednisone-equivalent for more than 6 weeks continuously prior to screening
- Received rituximab or other B-cell antibody within 52 weeks of screening or 26 weeks provided B cell reconstitution has occurred (i.e., CD19 count > 0.01x10^9/L); received anti-tumor necrosis factor (TNF) treatment, abatacept, alemtuzumab, intravenous immunoglobulin (IVIg), belimumab, tocilizumab, or eculizumab within 12 weeks prior to screening
- For patients scheduled to receive cyclophosphamide treatment, urinary outflow obstruction, active infection (especially varicella zoster infection), or platelet count <50,000/μL before start of dosing
- Participated previously in a CCX168 study
Data sourced from ClinicalTrials.gov (NCT02994927). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.