Efficacy and Safety Study of Apremilast to Treat Active Ulcerative Colitis (UC)

Amgen

Status and phase: Completed; Phase 2

Conditions: Ulcerative Colitis

Treatments: Drug: Placebo; Drug: Apremilast

Study type: Interventional

Funder types: Industry

Identifiers

NCT02289417

2014-002981-64 (EudraCT Number)

CC-10004-UC-001

Details and patient eligibility

About

The purpose of the study is to evaluate the clinical efficacy, safety and tolerability of apremilast (30 mg twice daily [BID] and 40 mg BID), compared with placebo, in participants with active Ulcerative Colitis (UC).

Full description

Approximately 165 participants (55 subjects per arm) will be randomized in a 1:1:1 ratio to receive oral apremilast (30 mg BID or 40 mg BID), or identically appearing placebo BID for up to 12 weeks, followed by 40 weeks of blinded treatment with apremilast (30 mg BID or 40 mg BID).

At the end of the Blinded Active-treatment Phase (Week 52), participants who have a Mayo endoscopy score ≤ 1 will have the opportunity to participate in the Extension Phase. Participants enrolled in the Extension Phase will receive apremilast for an additional 52 weeks (Weeks 52 to 104). With the implementation of Amendment 4, participants entering the Extension Phase will receive apremilast 30 mg BID. Subjects currently in the Extension Phase who are receiving apremilast 40 mg BID will be switched to 30 mg BID at the next scheduled visit.

Enrollment: 170 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Subjects must satisfy the following criteria to be enrolled in the study:

• Male or female aged 18 and over at the time of signing the informed consent.
• Must understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.
• Diagnosis of ulcerative colitis (UC) with a duration of at least 3 months prior to the Screening Visit..
• Total Mayo Score (TMS) ≥ 6 to ≤ 11 (range: 0-12) at baseline, prior to randomization in the study.
• Endoscopic subscore ≥ 2 (range: 0-3) on the Mayo score prior to randomization in the study.
• Subjects must have had a therapeutic failure, been intolerant to, or have a contraindication to, at least one of the following: oral aminosalicylates (ie, 5-aminosalicylic acid [5-ASA] compounds or sulfasalazine [SSZ]), budesonide, systemic corticosteroids, or immunosuppressants (eg, 6-mercaptopurine [6-MP], azathioprine [AZA], or methotrexate [MTX]).

Exclusion criteria

The presence of any of the following will exclude a subject from enrollment:

• Diagnosis of Crohn's disease, indeterminate colitis, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis.
• Ulcerative colitis restricted to the distal 15 cm or less (eg, ulcerative proctitis).
• Subjects who have had surgery as a treatment for UC or who, in the opinion of the Investigator, are likely to require surgery for UC during the study.
• Clinical signs suggestive of fulminant colitis or toxic megacolon.
• Prior use of any tumor necrosing factor (TNF) inhibitor (or any biologic agent).
• Prior use of mycophenolic acid, tacrolimus, sirolimus, cyclosporine or thalidomide.
• Use of intravenous (IV) corticosteroids within 2 weeks of the Screening Visit.
• Use of immunosuppressants (AZA, 6-MP or MTX) within 8 weeks of the Screening Visit.
• Use of topical treatment with 5-ASA or corticosteroid enemas or suppositories within 2 weeks of the Screening Visit.
• History of any clinically significant neurological, renal, hepatic, gastrointestinal, pulmonary, metabolic, cardiovascular, psychiatric, endocrine, hematological disorder or disease, or any other medical condition that, in the investigator's opinion, would preclude participation in the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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170 participants in 3 patient groups, including a placebo group

Apremilast 30 mg PO BID

Experimental group

Description:

Apremilast 30 mg by mouth (PO) twice a day (BID) for 12 weeks After 12 weeks: * Participants who achieve at least a 20% decrease from baseline in the total Mayo score (TMS) will continue to receive apremilast 30 mg BID for an additional 40 weeks. (Wk 52) * Participants who do not achieve at least a 20% decrease from baseline in the TMS will receive apremilast 40 mg BID for an additional 40 weeks (Wk 52) After 52 weeks, participants who are eligible for the Extension Phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)

Treatment:

Drug: Apremilast

Apremilast 40 mg PO BID

Experimental group

Description:

Apremilast 40 mg by mouth (PO) twice a day (BID) for 12 weeks After 12 weeks, participants assigned to the 40 mg BID dose of apremilast at baseline will continue to receive apremilast 40 mg BID for an additional 40 weeks (Wk 52) After 52 weeks, participants who are eligible for the extension Phase will continue to receive apremilast 40 mg BID for an additional 52 weeks (Wk 104)

Treatment:

Drug: Apremilast

Placebo BID

Placebo Comparator group

Description:

Identically matching placebo by mouth (PO) twice a day (BID) for 12 weeks. After 12 weeks all participants randomized to placebo at baseline will be re-randomized to receive apremilast 30 mg or 40 mg BID for an additional 40 weeks (Wk 52) After Wk 52, participants who are eligible for the extension phase will continue to receive the same dose of apremilast assigned at Wk 12 (30 mg BID or 40 mg BID) for an additional 52 weeks (Wk 104)

Treatment:

Drug: Placebo

Drug: Apremilast