A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Multiple Ascending Dose Study (Induction Therapy) & Long-term Extension Therapy of an Anti-OX40 Monoclonal Antibody (KHK4083) in Subjects With Moderately Active UC
Overview
- Phase
- Phase 2
- Intervention
- KHK4083
- Conditions
- Ulcerative Colitis
- Sponsor
- Kyowa Kirin, Inc.
- Enrollment
- 66
- Locations
- 1
- Primary Endpoint
- Number of Subjects With Treatment-related Adverse Events
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to determine the safety and tolerability of administration of multiple ascending doses of KHK4083 and to select the highest dose tolerated by subjects with moderately active Ulcerative Colitis (UC) followed by a Long-term Extension Therapy (LTE) phase for eligible subjects with a clinical response.
Detailed Description
A Phase 2, double-blind clinical study of multiple ascending doses of KHK4083 (or placebo) with an Long-term Extension Therapy (LTE) phase will be conducted in approximately 60 randomized adult subjects with moderately active UC who have a documented unsuccessful previous treatment. The Treatment Period includes double-blind Induction Therapy (12 weeks) and Open-label Therapy (OLE) phase (40 weeks) for eligible subjects at Week 12. Subjects already enrolled in the double-blind, long-term extension (LTE) under preceding versions of the protocol who worsen may be eligible to transition to the OLE up to Week 28. The Follow Up Period after the last administration will be for up to 16 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject is able and willing to comply with study procedures, and to adhere to dosing, visit schedules and follow-up procedures as described in the protocol and ICF;
- •Subject voluntarily signs/dates an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF in accordance with regulatory and Institutional Guidelines;
- •Male and female subjects ≥ 18 years of age at the time of enrollment;
- •Subject has UC that was diagnosed at least 6 months prior to the Screening visit;
- •Subject has moderately active UC with a total Mayo score of 4-9 and an endoscopic sub-score of at least 2, with disease that extends at least 15 cm from the anal verge;
- •Subject has had previous treatment (within 5 years prior to Screening) with one or more of the following: corticosteroids, immunosuppressive medications or TNF antagonist therapy that was unsuccessful because of a lack of efficacy response.
- •Female subjects (WOCBP) must have a negative pregnancy test at Screening and Baseline. WOCBP must agree to use effective contraception;
- •Male subjects (including those who have had a vasectomy) must use adequate contraception during the study and for at least 6 months after the last dose of investigational product.
Exclusion Criteria
- •Subject, who, for any reason, is judged by the Investigator to be inappropriate for this study;
- •Subject has a medical history of other clinically significant diseases/disorders;
- •Two or more biologic treatments with different mechanisms of action (e.g., infliximab, vedolizumab and golimumab) or Three or more anti-TNF biologics e.g. infliximab, adalimumab
- •Subject requires prescription treatment for UC, except for the stable, oral treatment of UC for 4 weeks prior to screening.
- •Subject has received any of the following prior treatments or treatments within the specified time prior to the Baseline visit:
- •Natalizumab, efalizumab, rituximab or other lymphocyte-depleting treatments, including but not limited, to alkylating agents (such as cyclophosphamide or chlorambucil) and total lymphoid irradiation at any time;
- •TNF antagonists within 8 weeks, or 5 half-lives (up to 12 weeks);
- •Vedolizumab within 16 weeks;
- •Methotrexate, cyclosporine, mycophenolate, tacrolimus, thalidomide, or other immune altering drugs within 4 weeks (ophthalmologic preparations are permitted);
- •5-ASA enema, steroid enema or suppository use within 2 weeks ; and/or Investigational agents within 8 weeks or 5 half-lives (whichever is longer).
Arms & Interventions
KHK4083 Cohort 1
Subjects received one 1.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
Intervention: KHK4083
KHK4083 Cohort 2
Subjects received one 3.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
Intervention: KHK4083
KHK4083 Cohort 3
Subjects received one 10.0 mg/kg IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
Intervention: KHK4083
KHK4083 Cohort 4
Subjects received one maximum tolerated dose (10.0 mg/kg) IV infusion treatment of KHK4083 every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48.
Intervention: KHK4083
Placebo
Subjects received one IV infusion treatment of Placebo every two weeks from Week 0 to Week 10 of Induction Therapy. Subjects who chose to continue into extension therapy and were eligible received one IV infusion every 4 weeks (at the same dose as Induction Therapy) from Week 12 to Week 48. Subjects who participated in Open-Label Therapy received KHK4083 instead of placebo.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Subjects With Treatment-related Adverse Events
Time Frame: Up to 52 weeks
To determine the safety and tolerability of KHK4083
Number of Subjects Who Show Improvement in the Mucosa at Week 12
Time Frame: 12 weeks
Measured by the modified Mayo endoscopy sub-score (mMES), which ranges from 0-3 with higher scores = more severe disease.
Number of Subjects With Treatment-related Serious Adverse Events
Time Frame: Up to 52 weeks
To determine the safety and tolerability of KHK4083
Proportion of Subjects Who Show Improvement in the Mucosa at Week 52
Time Frame: 52 weeks
Measured by the modified Mayo endoscopy sub-score (mMES), which ranges from 0-3 with higher scores = more severe disease.
Secondary Outcomes
- Number of Subjects Who Achieve Mucosal Healing at Week 12(12 weeks)
- Number of Subjects With Confirmed Anti-KHK4083 Antibodies (Immunogenicity)(52 weeks)
- Number of Subjects Who Achieve Mucosal Healing at Week 52(52 weeks)
- Number of Subjects Who Achieve Clinical Improvement at Week 12(12 weeks)
- Change From Baseline in Total Mayo Scale Score at Week 52(52 weeks)
- Number of Subjects Who Achieve a Clinical Response at Week 12(12 weeks)
- Number of Subjects Who Achieve a Clinical Response at Week 52(52 weeks)
- Number of Subjects Who Achieve Clinical Remission at Week 12(12 weeks)
- Number of Subjects Who Achieve Clinical Remission at Week 52(52 weeks)