Study of a Monoclonal Antibody KHK4083 in Moderate Ulcerative Colitis

• Register: ClinicalTrials.gov
• Last refreshed on: 6 May 2024
• Main ID: NCT02647866
• Date of registration: 08/12/2015
• Prospective Registration: Yes
• Primary sponsor: Kyowa Kirin, Inc.
• Public title: Study of a Monoclonal Antibody KHK4083 in Moderate Ulcerative Colitis
• Scientific title: 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
• Date of first enrolment: June 2016
• Target sample size: 66
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02647866
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Czech Republic, Czechia, Hungary, Poland, Puerto Rico, Romania, Russian Federation, Serbia, United States

Contacts

• Name: Vincent Strout, MBA
• Affiliation: Kyowa Kirin, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

1. 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;

2. Subject voluntarily signs/dates an Institutional Review Board (IRB)/Independent Ethics
Committee (IEC)-approved ICF in accordance with regulatory and Institutional
Guidelines;

3. Male and female subjects = 18 years of age at the time of enrollment;

4. Subject has UC that was diagnosed at least 6 months prior to the Screening visit;

5. 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;

6. 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.

7. Female subjects (WOCBP) must have a negative pregnancy test at Screening and Baseline.
WOCBP must agree to use effective contraception;

8. 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:

1. Subject, who, for any reason, is judged by the Investigator to be inappropriate for
this study;

2. Subject has a medical history of other clinically significant diseases/disorders;

3. 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

4. Subject requires prescription treatment for UC, except for the stable, oral treatment
of UC for 4 weeks prior to screening.

5. 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).

6. 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;

7. Subject with known colonic dysplasia, adenomas or polyposis;

8. Subject had major surgery within 4 weeks prior to Screening or an anticipated
requirement for major surgery;

9. Subject with enteric pathogens (including Clostridium difficile);

10. Subject with any of the following hematological and chemistry laboratory values:

- Platelet count < 100,000/mm3;

- Neutrophils < 1500/mm3;

- Serum creatinine = 1.6 mg/dL (= 144.4 µmol/L);

- Alkaline phosphatase > 3 times the upper limit of normal (ULN);

- AST or ALT > 2 times ULN;

- Total bilirubin > 2 mg/dL, unless due to Gilbert's Syndrome;

- Serum albumin < 3 g/dL;

- Hemoglobin < 9 g/dL;

- Glycated serum hemoglobin A1c = 9%.

11. Subject has clinically significant cardiac disease;

12. Subject is pregnant or breastfeeding;

13. Subject has had major immunologic reaction;

14. Subject is Hepatitis B core antibody or surface antigen positive and/or Hepatitis C
antibody positive with detectable RNA;

15. Subject has a history of human immunodeficiency virus (HIV) positivity, tests positive
for HIV, or has congenital or acquired immunodeficiency;

16. Subject has or has had active TB, suspected extra-pulmonary TB, a history of
incompletely treated TB, or latent TB or other latent infection. Subjects with latent
TB (clinical findings, purified protein derivative [PPD] or interferon gamma release
assay [IGRA]) may be included in the study if prophylactic therapy for latent TB is
started at least 4 weeks prior to Screening. Subjects with a potentially untreated
other infection (clinical findings) are to be excluded.

17. Subject has bacterial infections requiring treatment with oral or parenteral
antibiotics, within 2 and 4 weeks, respectively.

18. Subject has a history of systemic opportunistic infection or recurrent infections

19. Subject has malignancy or history of malignancy, except for adequately treated basal
cell skin cancer or adequately treated carcinoma in-situ of the cervix without
recurrence at least 5 years.

20. Subject who received a bacille Calmette-Guérin (BCG) vaccine within 6 months of
randomization or live vaccination (e.g., measles, mumps, rubella [MMR]; herpes zoster;
varicella, intranasal influenza; and oral poliomyelitis) within 4 weeks of
randomization.

21. Subject with a history of or active substance abuse.

22. Subject has other severe acute or chronic medical or psychiatric condition or
laboratory abnormality.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Digestive System Diseases

Gastrointestinal Diseases

Colonic Diseases

Inflammatory Bowel Diseases

Abdominal Pain

Autoimmune Disease

Intestinal Diseases

Ulcerative Colitis

Colitis

Colitis, Ulcerative

Intervention(s)

Drug: KHK4083

Drug: Placebo

Primary Outcome(s)

Number of Subjects With Treatment-related Serious Adverse Events [Time Frame: Up to 52 weeks]

Number of Subjects Who Show Improvement in the Mucosa at Week 12 [Time Frame: 12 weeks]

Number of Subjects With Treatment-related Adverse Events [Time Frame: Up to 52 weeks]

Proportion of Subjects Who Show Improvement in the Mucosa at Week 52 [Time Frame: 52 weeks]

Secondary Outcome(s)

Change From Baseline in Total Mayo Scale Score at Week 52 [Time Frame: 52 weeks]

Number of Subjects Who Achieve Clinical Improvement at Week 12 [Time Frame: 12 weeks]

Number of Subjects Who Achieve Clinical Remission at Week 12 [Time Frame: 12 weeks]

Number of Subjects Who Achieve Clinical Remission at Week 52 [Time Frame: 52 weeks]

Number of Subjects Who Achieve a Clinical Response at Week 12 [Time Frame: 12 weeks]

Number of Subjects Who Achieve a Clinical Response at Week 52 [Time Frame: 52 weeks]

Number of Subjects Who Achieve Mucosal Healing at Week 52 [Time Frame: 52 weeks]

Number of Subjects With Confirmed Anti-KHK4083 Antibodies (Immunogenicity) [Time Frame: 52 weeks]

Number of Subjects Who Achieve Mucosal Healing at Week 12 [Time Frame: 12 weeks]

Secondary ID(s)

4083-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/03/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02647866