Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication TAVNEOS is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. TAVNEOS does not eliminate glucocorticoid use. FDA label
Also known as TAVNEOS, AMG 569, CCX168
Avacopan · 16 trials · 14 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.
The mean change in the slope of the urinary protein:creatinine ratio (UPCR, in mg/g/week) between the 8-week run-in period and the 12-week treatment period
Acronyms use: Adverse Events (AE's) Serious Adverse Events (SAE's)
Acronyms use: Adverse Events (AE's) Serious Adverse Events (SAE's)
This is a safety study to assess the overall rates of treatment-emergent adverse events (TEAEs) across all study arms.
Proportion of Patients achieving 50% reduction in the Birmingham Vasculitis Activity Score \[BVAS\] at Day 85 and no worsening in any body system component at day 85
Disease response is defined as BVAS percentage reduction from baseline of at least 50% plus no worsening in any body system component.
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 |
| CCX168 (Avacopan) | EXPERIMENTAL | CCX168 (Avacopan) plus stable dose of RAAS blocker |
| CCX168 low dose plus standard of care | ACTIVE_COMPARATOR | Capsule, 10 mg, twice daily + standard of care for 12 weeks |
| CCX168 high dose plus standard of care | ACTIVE_COMPARATOR | Capsule, 30 mg, twice daily + standard of care for 12 weeks |
| Placebo, twice daily + standard of care | PLACEBO_COMPARATOR | Capsule, placebo, twice daily + standard of care for 12 weeks |
| CCX168 | EXPERIMENTAL | 30 mg Active study medication, plus either two-thirds reduced dose of oral glucocorticoids for step 1 of the study, or no oral glucocorticoids for step 2 of the study |
| 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). |
| 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. |
| Cohort A: Single Oral Dosing of CCX168 in Japanese Adult Males | EXPERIMENTAL | Healthy Japanese adult males will receive 1 of 3 single oral doses of CCX168 (10 mg, 30 mg or 100 mg) or placebo. Each dose level will be administered under fasted conditions. Single doses of CCX168 30 mg will be administered under fasted and fed conditions. |
| Cohort B: Multiple Oral Dosing of CCX168 in Japanese Adult Males | EXPERIMENTAL | Healthy Japanese adult males will receive 1 of 2 oral doses of CCX168 (30 mg or 50 mg) or placebo twice-daily for 7 days under fed conditions. |
| Cohort C: Single Oral Dosing of CCX168 in Caucasian Adult Males | EXPERIMENTAL | Healthy Caucasian adult males will receive 1 of 2 single oral doses of CCX168 (10 mg or 30 mg) or placebo under fasted conditions. |
| Cohort D: Multiple Oral Dosing of CCX168 in Caucasian Adult Males | EXPERIMENTAL | Healthy Caucasian adult males will receive an oral dose of CCX168 30 mg or placebo twice-daily for 7 days under fed conditions. |
| Cohort A | EXPERIMENTAL | A single dose of 2 mg midazolam (a Cytochrome P450 \[CYP\]3A4 probe drug) and a single dose of 200 mg celecoxib (a CYP2C9 probe drug) will be given orally concurrently on Day 1 and Day 13. On Day 3 through Day 18, CCX168 will be given orally at 30 mg twice daily (b.i.d.), and a single dose of 30 mg CCX168 will be given in the morning on Day 19. On Day 16 through Day 19, a once daily (q.d.) dose of 200 mg itraconazole (a CYP3A4 inhibitor) will be given orally. |
| Cohort B | EXPERIMENTAL | A single dose of 30 mg CCX168 will be given on Day 1 and Day 14, while rifampicin (a CYP3A4 inducer) will be given at 600 mg once daily from Day 4 through Day 17. |
| Cohort 1: Sequence ABCD | EXPERIMENTAL | Participants assigned to sequence ABCD will receive the following treatments: Period 1: Single dose of 30 mg CCX168 after a high-fat, high-calorie meal (Treatment A). Period 2: After a washout period of ≥ 10 days, single dose of 30 mg CCX168 in the fasted state (Treatment B). Period 3: After a washout period of ≥ 10 days, single dose of 3 mg CCX168 in the fasted state (Treatment C). Period 4: 24 hours after the 3 mg CCX168 dose in Period 3, single dose of 100 mg CCX168 on Day 1, and then 100 mg CCX168 twice daily from Day 2 through Day 6. On Day 7, only a morning dose of 100 mg CCX168 (Treatment D). |
| Cohort 2: Sequence BACD | EXPERIMENTAL | Participants assigned to sequence BACD will receive the following treatments: Period 1: Single dose of 30 mg CCX168 in the fasted state (Treatment B). Period 2: After a washout period of ≥ 10 days, single dose of 30 mg CCX168 after a high-fat, high-calorie meal (Treatment A). Period 3: After a washout period of ≥ 10 days, single dose of 3 mg CCX168 in the fasted state (Treatment C). Period 4: 24 hours after the 3 mg CCX168 dose in Period 3, single dose of 100 mg CCX168 on Day 1, and then 100 mg CCX168 twice daily from Day 2 through Day 6. On Day 7, only a morning dose of 100 mg CCX168 (Treatment D). |
| [14C]CCX168 | EXPERIMENTAL | Participants will receive a single oral dose of \[14C\]CCX168 100 mg containing 400 μCi of \[14C\] on Day 1. |
| Cohort 1 | EXPERIMENTAL | During Period 1, participants will receive a single dose of CCX168 1 mg or placebo. During the second study period, participants will receive the same dose as during the first period but once daily (QD) for a period of 7 days continuously. |
| Cohort 2 | EXPERIMENTAL | During Period 1, participants will receive a single dose of CCX168 3 mg or placebo. During the second study period, participants will receive the same dose as during the first period but QD for a period of 7 days continuously. |
| Cohort 3 | EXPERIMENTAL | During Period 1, participants will receive a single dose of CCX168 10 mg or placebo. During the second study period, participants will receive the same dose as during the first period but QD for a period of 7 days continuously. |
| Cohort 4 | EXPERIMENTAL | During Period 1, participants will receive a single dose of CCX168 30 mg or placebo. During the second study period, participants will receive the same dose as during the first period or placebo twice daily (BID) for a period of 7 days continuously. |
| Cohort 5 | EXPERIMENTAL | During Period 1, participants will receive a single dose of CCX168 100 mg or placebo. During the second study period, participants will receive the same dose as during the first period or placebo BID for a period of 7 days continuously. |
| 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 |
| CCX168 | DRUG | CCX168 30 mg, twice daily (b.i.d.) orally for 84 days (12 weeks). The CCX168 dose was taken in the morning, optimally within one hour after breakfast, and in the evening, optimally within one hour after dinner. |
| CCX168 10 mg, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids | DRUG | - |
| CCX168 30 mg, twice daily, cyclophosphamide/rituximab plus glucocorticoids | DRUG | - |
| Placebo, twice daily, plus cyclophosphamide/rituximab plus glucocorticoids | OTHER | - |
| Moxifloxacin | DRUG | Administered orally. |
| Placebo for avacopan | DRUG | Administered orally. |
| Placebo for moxifloxacin | DRUG | Administered orally. |
| Midazolam | DRUG | Administered orally. |
| Celecoxib | DRUG | Administered orally. |
| Itraconazole | DRUG | Administered orally. |
| Rifampicin | DRUG | Administered orally. |
| [14C]CCX168 | 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 used to treat ANCA-associated vasculitis, a group of autoimmune conditions that includes granulomatosis with polyangiitis. It is also being studied in C3 glomerulopathy and in children with ANCA-associated vasculitis. Amgen Inc. develops the drug under the ticker AMGN.
Avacopan targets C5AR1, the C5a receptor 1, and acts as an antagonist. By blocking this receptor, the drug is designed to interfere with the complement-driven inflammation that contributes to ANCA-associated vasculitis and related conditions. It is a small molecule administered as an oral therapy.
Avacopan is developed by Amgen Inc., which trades under the ticker AMGN. Amgen is the company responsible for the clinical development program, including the Phase 3 pediatric study and the earlier-phase pharmacokinetic studies in renal and hepatic impairment.
Avacopan is in Phase 3 development. A Phase 3 trial is evaluating it in combination with a rituximab or cyclophosphamide-containing regimen in children aged 6 to under 18 years with ANCA-associated vasculitis. Earlier Phase 1 and Phase 2 studies have also been conducted.
Avacopan has been studied in several registered trials. These include NCT06321601, a Phase 3 pediatric study in ANCA-associated vasculitis; NCT07176546, a Phase 2 trial in otolaryngologic manifestations of granulomatosis with polyangiitis; NCT06468826, a Phase 1 study in end-stage renal disease; and NCT06004934, a Phase 1 study in hepatic impairment.
Yes, Avacopan is also known as CCX168. The two names refer to the same investigational small-molecule C5AR1 antagonist developed by Amgen Inc. for ANCA-associated vasculitis and related complement-mediated conditions.