Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Avacopan · 9 trials · 12 indications
Disease remission at Week 26 was defined as: * Achieving a BVAS of 0 as determined by the Adjudication Committee; * No administration of glucocorticoids given for ANCA-associated vasculitis within 4 weeks prior to Week 26; * No BVAS \>0 during the 4 weeks prior to Week 26 (if collected for an unscheduled assessment).
Sustained remission at Week 52 was defined as: * Disease remission at Week 26 as defined above; * Disease remission at Week 52 defined as a BVAS of 0 at Week 52 as determined by the Adjudication Committee and no administration of glucocorticoids for treatment of ANCA-associated vasculitis within 4 weeks prior to Week 52; * No disease relapse between Week 26 and Week 52 as determined by the Adjudication Committee.
The proportion of patients in ENT remission without relapse in each treatment group at week 52 with no glucocorticoid (GC) exposure 4 weeks prior to week 52, where ENT remission is defined as a score of 0 on GPA ENT disease activity score
The percentage of subjects achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12 in the ITT1 population using the NRI-CMH Test. A response was defined as a reduction of at least 50 in abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count compared with baseline. The ITT1 population was defined as all subjects who were randomized at baseline and received at least 1 dose of investigational product during period 1. NRI- non-responder imputation; CMH- Cochran-Mantel-Haenszel. Percentage values have been reported as opposed to proportion values to allow for statistical analyses.
Change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease activity - Subjects with Elevated C5b-9 (\> 244 ng/mL) in the Intent-to-Treat Population. C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement. C3G=C3 glomerulopathy
Percent change from baseline to Week 26 in the biopsy-based C3G Histologic Index for disease activity - Combined C5b-9 Strata (elevated \[\> 244 ng/mL\] and non-elevated C5b-9) in the Intent-to-Treat Population. C3G Histological Index for Disease Activity Scores can range from 0 to 21. A decrease indicates improvement. C3G=C3 glomerulopathy \* Multiple Imputation: Missing Week 26 values are imputed using the regression method to create 100 complete datasets.
Cmax was obtained using noncompartmental analysis.
Cmax was obtained using noncompartmental analysis.
AUClast was obtained using noncompartmental analysis.
AUClast was obtained using noncompartmental analysis.
AUCinf was obtained using noncompartmental analysis.
AUCinf was obtained using noncompartmental analysis.
AUC0-48 was obtained using noncompartmental analysis.
AUC0-48 was obtained using noncompartmental analysis.
CLD determines how much of the drug is removed by hemodialysis.
CLD determines how much of the drug is removed by hemodialysis.
| Arm | Type | Description |
|---|---|---|
| Avacopan | EXPERIMENTAL | Participants will receive avacopan twice-daily (BID) administered as oral tablets or liquid formula for 52 weeks. |
| Prednisone group | ACTIVE_COMPARATOR | Avacopan-matching placebo plus cyclophosphamide/azathioprine or rituximab plus a full starting dose of prednisone. |
| Avacopan group | EXPERIMENTAL | Avacopan plus cyclophosphamide/azathioprine or rituximab plus prednisone-matching placebo. |
| TAVNEOS | ACTIVE_COMPARATOR | BID dose of 30 mg TAVNEOS |
| Placebo | PLACEBO_COMPARATOR | BID dose of 30 mg TAVNEOS-matching placebo |
| Group A | PLACEBO_COMPARATOR | Placebo twice daily (BID) for Period 1 of the study |
| Group B | EXPERIMENTAL | Avacopan 10 mg twice daily (BID) for Period 1+2 of the study |
| Group C | EXPERIMENTAL | Avacopan 30 mg twice daily (BID) for Period 1+2 of the study |
| Placebo to Avacopan 10 mg | EXPERIMENTAL | Treatment period 2, subjects randomized to placebo during period 1 were rerandomized 1:1 to receive 10 mg or 30 mg avacopan BID in period 2. |
| Placebo to Avacopan 30 mg | EXPERIMENTAL | Treatment period 2, subjects randomized to placebo during period 1 were rerandomized 1:1 to receive 10 mg or 30 mg avacopan BID in period 2. |
| Avacopan Matching Placebo | PLACEBO_COMPARATOR | Matching placebo capsules x 3 administered twice daily during the 26 week blinded treatment period period |
| Group 1: Normal Renal Function | EXPERIMENTAL | Participants in Group 1 will receive a single dose of avacopan on Day 1. |
| Group 2: ESRD Requiring HD | EXPERIMENTAL | Participants in Group 2 will receive a single dose of avacopan on Day 1 in each of 2 treatment periods (Period 1/on HD and Period 2/off HD). |
| Arm 1: Avacopan and Simvastatin | EXPERIMENTAL | A single dose of 40 mg simvastatin will be given orally in the morning on Day 1 and Day 10. The Day 10 dose of simvastatin will be co-administered with the morning dose of avacopan. On Days 3 through 11, avacopan will be given orally at 30 mg BID. |
| Arm 2: Avacopan and Simvastatin | EXPERIMENTAL | A single dose of 40 mg simvastatin will be given orally in the morning on Day 1 and Day 10. The Day 10 dose of simvastatin will be co-administered with the morning dose of avacopan. On Days 3 through 11, avacopan will be given orally at 60 mg BID. |
| Cohort 1: Avacopan | EXPERIMENTAL | Participants will be randomized to receive multiple doses of avacopan orally twice daily (BID): 30 mg for 7 days and 100 mg for 7 days, for a total of 14 dosing days, and placebo for moxifloxacin on Days 1 and 15. |
| Cohort 2A: Moxifloxacin/Placebo | ACTIVE_COMPARATOR | Participants will be randomized to receive moxifloxacin 400 mg orally on Day 1, placebo for avacopan BID on Days 1 to 14, and placebo for moxifloxacin on Day 15. |
| Cohort 2B: Placebo/Moxifloxacin | ACTIVE_COMPARATOR | Participants will be randomized to receive placebo for moxifloxacin orally on Day 1, placebo for avacopan BID on Days 1 to 14, and moxifloxacin 400 mg orally on Day 15. |
| Group 1: Mild Hepatic Impairment | EXPERIMENTAL | Participants with mild hepatic impairment (defined using Child-Pugh Classification of the Severity of Liver Disease \[C-P\] criteria \[C-P Class A, score of 5 to 6 points\]) will receive a single oral dose of 30 mg avacopan on Day 1 in the fasted state. |
| Group 2: Moderate Hepatic Impairment | EXPERIMENTAL | Participants with moderate hepatic impairment (defined using the C-P criteria \[C-P Class B, score of 7 to 9 points\]) will receive a single oral dose of 30 mg avacopan on Day 1 in the fasted state. |
| Group 3: Healthy Control Group | ACTIVE_COMPARATOR | Participants with normal hepatic function (medically normal with no clinically significant illness or disease or abnormal physical examination findings, and with normal laboratory values at screening) will be demographically-matched to participants in Group 1 and Group 2, and will receive a single oral dose of 30 mg avacopan on Day 1 in the fasted state. |
| Name | Type | Description |
|---|---|---|
| Avacopan | DRUG | Oral administration |
| Prednisone | DRUG | Avacopan-matching placebo twice daily orally for 52 weeks (364 days): \- Three avacopan-matching placebo capsules in the morning, preferably with food, and three in the evening, preferably with food, approximately 12 hours after the morning dose. Oral prednisone tapering regimen over 20 weeks (140 days): * Prednisone 60 mg per day if the subject's body weight was ≥55 kg, or 45 mg per day if the subject's body weight was \<55 kg, starting on Day 1 with tapering according to the protocol-specified schedule. * Adolescents who weighed ≤37 kg started at a prednisone dose of 30 mg per day. |
| Cyclophosphamide | DRUG | Orally or intravenously administered |
| Rituximab | BIOLOGICAL | Intravenously administered |
| Azathioprine | DRUG | Orally administered |
| Placebo | DRUG | BID dose of 30mg TAVNEOS-matching placebo (3-10mg capsules) |
| Avacopan Matching Placebo | DRUG | avacopan matching placebo |
| Simvastatin | DRUG | Orally via tablets |
| Moxifloxacin | DRUG | Administered orally. |
| Placebo for avacopan | DRUG | Administered orally. |
| Placebo for moxifloxacin | DRUG | Administered orally. |
Inclusion Criteria: * Male and female children and adolescents from 6 to \< 18 years old of age. * Clinical diagnosis of Granulomatosis with Polyangiitis (GPA) or microscopic polyangiitis (MPA), consistent with Chapel-Hill Consensus Conference definitions (Jennette et al, 2013). * Positive anti-PR3...
Avacopan is an investigational small molecule being developed for ANCA-Associated Vasculitis, Hidradenitis Suppurativa, Vasculitis, Granulomatosis With Polyangiitis, and End-Stage Renal Disease (ESRD). It is also being studied in C3 Glomerulopathy and hepatic impairment. The drug is in Phase 3 clinical development for vasculitis indications.
Avacopan is being developed by Amgen Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol AMGN. The company is conducting clinical trials of Avacopan across multiple indications, including vasculitis and renal impairment, with studies in both adult and pediatric populations.
Avacopan is in Phase 3 clinical development for vasculitis, including a pediatric study in children aged 6 to under 18 years. It has also completed Phase 1 and Phase 2 trials for other conditions. The drug is investigational and not yet approved by regulatory authorities.
Avacopan has been studied in several clinical trials. NCT03301467 was a completed Phase 2 trial in C3 Glomerulopathy with 57 participants. NCT06004934 was a completed Phase 1 pharmacokinetic study in hepatic impairment. NCT06321601 is an active Phase 3 trial in pediatric vasculitis. NCT06468826 was a completed Phase 1 study in ESRD.
Yes, Avacopan is being studied in children. NCT06321601 is an active Phase 3 trial evaluating Avacopan in combination with rituximab or cyclophosphamide-containing regimens in children aged 6 to under 18 years with vasculitis. This trial is currently active but not recruiting participants.
Avacopan is a small molecule immunology therapeutic. It targets the complement system, specifically the C5a receptor, to modulate inflammatory responses. This mechanism is relevant to its study in complement-mediated diseases like C3 Glomerulopathy and ANCA-Associated Vasculitis.