Study of a Monoclonal Antibody KHK4083 in Moderate Ulcerative Colitis

NCT02647866 | Completed Phase 2 Results

• 1 other identifier: 4083-002
• Study Type: interventional
• Target: 66
• Locations: 7 countries
• Sites: 23

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.

Conditions

Ulcerative Colitis; Digestive System Diseases; Colitis, Ulcerative; Colitis; Gastrointestinal Diseases; Inflammatory Bowel Diseases; Intestinal Diseases; Colonic Diseases; Autoimmune Disease; Abdominal Pain

Keywords

4083-002; Intestinal Diseases; Ulcerative Colitis; UC; Mayo Clinic Scoring; Gastrointestinal Tract

Outcome Measures

Primary Outcomes (4)

• Number of Subjects With Treatment-related Adverse Events

  To determine the safety and tolerability of KHK4083

  Up to 52 weeks

• Number of Subjects With Treatment-related Serious Adverse Events

  To determine the safety and tolerability of KHK4083

  Up to 52 weeks

• Number of Subjects Who Show Improvement in the Mucosa at Week 12

  Measured by the modified Mayo endoscopy sub-score (mMES), which ranges from 0-3 with higher scores = more severe disease.

  12 weeks

• Proportion of Subjects Who Show Improvement in the Mucosa at Week 52

  Measured by the modified Mayo endoscopy sub-score (mMES), which ranges from 0-3 with higher scores = more severe disease.

  52 weeks

Secondary Outcomes (9)

• Number of Subjects With Confirmed Anti-KHK4083 Antibodies (Immunogenicity)

  52 weeks

• Number of Subjects Who Achieve Mucosal Healing at Week 12

  12 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

Study Arms (5)

KHK4083 Cohort 1

EXPERIMENTAL

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.

Drug: KHK4083

KHK4083 Cohort 2

EXPERIMENTAL

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.

Drug: KHK4083

KHK4083 Cohort 3

EXPERIMENTAL

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.

Drug: KHK4083

KHK4083 Cohort 4

EXPERIMENTAL

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.

Drug: KHK4083

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

KHK4083 DRUG

IV Infusion

KHK4083 Cohort 1; KHK4083 Cohort 2; KHK4083 Cohort 3; KHK4083 Cohort 4

Placebo DRUG

IV Infusion

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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);
• ASA enema, steroid enema or suppository use within 2 weeks ; and/or Investigational agents within 8 weeks or 5 half-lives (whichever is longer).
• Subject with recent, suspected or confirmed symptomatic stenosis of the colon, abdominal abscess, or ischemic colitis based on clinical or radiographic data; a history of toxic megacolon; or who had any previous surgery for UC;
• Subject with known colonic dysplasia, adenomas or polyposis;
• Subject had major surgery within 4 weeks prior to Screening or an anticipated requirement for major surgery;
• Subject with enteric pathogens (including Clostridium difficile);
• Subject with any of the following hematological and chemistry laboratory values:

Sponsors & Collaborators

• Kyowa Kirin, Inc.: lead

Study Sites (23)

Unknown Facility

Greenville, South Carolina, 29615, United States

Location

Unknown Facility

Hradec Králové, 500 12, Czechia

Location

Unknown Facility

Znojmo, 669 02, Czechia

Location

Unknown Facility

Budapest, 1125, Hungary

Location

Unknown Facility

Budapest, H-1032, Hungary

Location

Unknown Facility

Budapest, H-1083, Hungary

Location

Unknown Facility

Bydgoszcz, 85-168, Poland

Location

Unknown Facility

Rzeszów, 35-302, Poland

Location

Unknown Facility

Sopot, 81-756, Poland

Location

Unknown Facility

Tychy, 43-100, Poland

Location

Unknown Facility

Warsaw, 00-632, Poland

Location

Unknown Facility

Warsaw, 03-580, Poland

Location

Unknown Facility

Warsaw, 54-239, Poland

Location

Unknown Facility

Bucharest, Sector 2, 020125, Romania

Location

Unknown Facility

Krasnoyarsk, 660022, Russia

Location

Unknown Facility

Moscow, 129110, Russia

Location

Unknown Facility

Novosibirsk, 630091, Russia

Location

Unknown Facility

Penza, 440026, Russia

Location

Unknown Facility

Saint Petersburg, 194354, Russia

Location

Unknown Facility

Saint Petersburg, 196247, Russia

Location

Unknown Facility

Zemun, Belgrade, 11080, Serbia

Location

Bežanija Kosa

Belgrade, 11080, Serbia

Location

Unknown Facility

Kragujevac, 34 000, Serbia

Location

MeSH Terms

Conditions

Colitis, Ulcerative; Digestive System Diseases; Colitis; Gastrointestinal Diseases; Inflammatory Bowel Diseases; Intestinal Diseases; Colonic Diseases; Autoimmune Diseases; Abdominal Pain

Interventions

KHK4083

Condition Hierarchy (Ancestors)

Gastroenteritis; Immune System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Digestive

Results Point of Contact

• Title: Kyowa Kirin Pharmaceutical Development
• Organization: Kyowa Kirin Pharmaceutical Development

kkd.clintrial.82@kyowakirin.com

609-919-1100

Study Officials

• Vincent Strout, MBA

  Kyowa Kirin, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind Induction Therapy was separated into Part A for administration of multiple ascending IV doses of KHK4083 (or placebo) to subjects in Cohorts 1-3 and Part B for administration of the maximally tolerated dose (as determined in cohorts 1-3) in expansion cohort 4. Subjects in Part A were prohibited from participating in Part B. Subjects in each cohort were randomly assigned in a 3:1 ratio to receive KHK4083 or placebo by IV infusion over 60 minutes (± 10 min.). Each subject received a total of 6 treatments (1 IV infusion per treatment) every 2 weeks from Week 0 (Day 1) to Week 10. Subjects who completed double-blind Induction Therapy (i.e., at least 5 of 6 treatments) and had a clinical response or mucosal healing, as defined above, were eligible to continue in double-blind Long Term Extension Therapy (Weeks 12-52) \& after protocol amendment all subjects who received at least 5 of 6 treatments were eligible for Open Label Extension Therapy (Weeks 12-52).

Study Record Dates

• First Submitted: December 8, 2015
• First Posted: January 6, 2016
• Study Start: June 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: October 1, 2018
• Last Updated: April 26, 2024
• Results First Posted: March 5, 2020

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (3); PL (7); CZ (2); RO (1); US (1); HU (3); RU (6)