Evaluation of Safety and Efficacy of Avacopan in Subjects With Moderate to Severe Hidradenitis Suppurativa (AURORA)

Amgen435 enrolled

Overview

Phase 2 study of Avacopan in Subjects with Moderate to Severe Hidradenitis Suppurativa

A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 2 study in subjects with moderate to severe Hidradenitis Suppurativa. The study is multicenter and will consist of three subject groups. Subjects will be randomized 1:1:1 to a treatment of 10mg avacopan twice daily, 30 mg avacopan twice daily or placebo twice daily for 12 weeks. Following the 12 weeks double-blind treatment period, subjects on placebo will be re-randomized 1:1 to receive 10 mg or 30 mg avacopan twice daily for additional 24 weeks. Subjects treated with avacopan will continue to receive the same dose (either 10 mg or 30 mg twice daily) for additional 24 weeks. Subjects will be on study treatment for 36 weeks and will be followed for 44 weeks for assessment of safety and efficacy. Study acquired by Amgen and all disclosures were done by previous sponsor ChemoCentryx. Primary efficacy analysis will be at 12 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

435

Conditions

Hidradenitis Suppurativa Acne Inversa

Interventions

AvacopanDRUG

Active treatment

PlaceboOTHER

Placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * At least 18 years of age * Clinical diagnosis of HS (Hurley Stage II or III), confirmed by a dermatologist, for at least 6 months prior to Screening * HS lesions are present in at least 2 distinct anatomic areas * Inadequate or loss of response to a systemic course of antibiotics typically of at least 90 days * Must have at least 5 inflammatory nodules or abscesses at screening * Use adequate birth control for subject and partners of child bearing potential * Willing and able to give written Informed Consent Exclusion Criteria: * Pregnant or breast-feeding * Any other skin disease that may interfere with the assessment of HS * Rapidly progressive, expanding HS within 30 days prior to screening * More than 20 draining fistulae at screening * Any anti-TNF-α treatment for HS or for other conditions prior to Day 1 visit will be prohibited. Exception: Subjects who were previously treated with an anti-TNF-α drug and discontinued treatment \>12 weeks prior to Day 1 visit are allowed for enrollment * Systemic antibiotics are generally excluded * Topical antibiotics use within 14 days prior to Day 1 is excluded * Have started a topical prescription medicine for HS within 14 days prior to screening * A systemic medicine for HS, including biologics and other systemic therapies * Have received within 14 days prior to Day 1 visit or is expected to require oral or transdermal opioid analgesics (except for tramadol) for any reason

Locations (91)

Outcomes

Primary Outcomes

Percentage of Subjects Achieving Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12.

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.

Time frame: Baseline to Week 12

Secondary Outcomes

Change From Baseline in Total AN Count at Week 12

The Change from Baseline in total AN (abscess and inflammatory nodule) count at Week 12 using MMRM and OC in the ITT1 population. 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. MMRM - mixed effects model for repeated measures; OC- observed case

Time frame: Baseline to Week 12

Number of Responders Achieving at Least 30% Reduction and at Least 1 Unit Reduction From Baseline in the Subject's Global Assessment of Skin Pain (NRS30) in Subjects With a Baseline NRS of at Least 3, Evaluated at Week 12

NRS30 = The number of responders achieving at least 30% reduction and at least 1 unit reduction from baseline in the subject's global assessment of skin pain score. Percentage is based on the number of subjects with a baseline pain score of at least 3 in each treatment group. Weekly averages of daily pain will be calculated based on subjects' daily diary recording of the worst pain experienced in the previous 24 hours. 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

Time frame: Baseline to Week 12

Data from ClinicalTrials.gov

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Clinical Site

Birmingham, Alabama, United States

Clinical Site

Birmingham, Alabama, United States

Clinical Site

Mobile, Alabama, United States

Clinical Site

Phoenix, Arizona, United States

Clinical Site

Scottsdale, Arizona, United States

Clinical Site

Fort Smith, Arkansas, United States

Clinical Site

Rogers, Arkansas, United States

Clinical Site

Fountain Valley, California, United States

Clinical Site

Fremont, California, United States

Clinical Site

Fullerton, California, United States

...and 81 more locations

Area Under the Curve From Time 0-3hrs (AUC 0-3hrs) of Metabolite M1 Plasma Concentration on Day 1

The Area under the curve from Time 0-3hrs (AUC 0-3hrs) of Metabolite M1 plasma concentration on Day 1 in the PK population. PK- pharmacokinetics

Time frame: Day 1

Number of Responders With Baseline Hurley Stage II Who Achieved an AN Count of 0, 1, or 2 at Week 12

The number of responders With Baseline Hurley Stage II Who Achieved an Abscess and Inflammatory Nodule (AN) Count of 0, 1, or 2 at Week 12 using the NRI-CMH Test in the ITT1 population. Hurley Stage II disease is defined as having 1 or more widely separated recurrent abscesses with tract formation and scars. 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.

Time frame: Baseline and Week 12

Change of IHS4 Score Relative to Baseline at Week 12.

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. IHS4 score (points) = (number of nodules multiplied by 1) + (number of abscesses multiplied by 2) + \[number of draining tunnels (fistulae/sinuses) multiplied by 4\]. A score of 3 or less signifies mild HS, a score of 4-10 signifies moderate HS and a score of 11 or higher signifies severe HS. IHS4- International HS Severity Scoring System

Time frame: Baseline and Week 12

Change From Baseline in Inflammatory Nodule Count at Week 12

A reduction in AN signifies improvement. 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.

Time frame: Baseline and Week 12

Change From Baseline in Abscess Count at Week 12

A reduction in abscess count signifies improvement. 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.

Time frame: Baseline and Week 12

Change From Baseline in Draining Fistula Count at Week 12

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.

Time frame: Baseline and Week 2, Week 4, Week 8 and Week 12

Change From Baseline to Week 12 in the Modified Sartorius Score to Quantify the Severity Change of HS

Twelve body areas will be evaluated to calculate the Sartorius and modified Sartorius scores: left and right axillae, left and right inframammary areas, intermammary area, left and right buttocks, left and right inguinocrural folds, perianal area, perineal area, and other. The presence of nodules, abscesses, fistulae, scars, and other findings will be recorded. The longest distance between two lesions and whether lesions are separated by normal skin is recorded. A score of 4 indicates the least severe disease, and higher scores indicate increasingly severe disease. There is no upper limit in the score. 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.

Time frame: Baseline and Week 2, Week 4, Week 8 and Week 12