Ulcerative Colitis Clinical Trial
Official 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
NCT number | NCT02647866 |
Other study ID # | 4083-002 |
Secondary ID | |
Status | Completed |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | June 2016 |
Est. completion date | October 2018 |
Verified date | April 2024 |
Source | Kyowa Kirin Co., Ltd. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 66 |
Est. completion date | October 2018 |
Est. primary completion date | September 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Serbia | Bežanija Kosa | Belgrade |
Lead Sponsor | Collaborator |
---|---|
Kyowa Kirin, Inc. |
United States, Czechia, Hungary, Poland, Romania, Russian Federation, Serbia,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Subjects With Treatment-related Adverse Events | To determine the safety and tolerability of KHK4083 | Up to 52 weeks | |
Primary | Number of Subjects With Treatment-related Serious Adverse Events | To determine the safety and tolerability of KHK4083 | Up to 52 weeks | |
Primary | 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 | |
Primary | 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 | Number of Subjects With Confirmed Anti-KHK4083 Antibodies (Immunogenicity) | The immunogenicity was assessed by determination of the development of anti-drug antibodies (ADA) against KHK4083. | 52 weeks | |
Secondary | Number of Subjects Who Achieve Mucosal Healing at Week 12 | The endoscopic Mayo Score (Mayo endoscopic subscore) evaluates ulcerative colitis stage, based only on endoscopic exploration. The scale ranges from 0 to 3, with higher scores = more severe activity. Mucosal healing is defined as modified Mayo endoscopy sub-score (mMES) of 0 or 1 at Week 12. | 12 weeks | |
Secondary | Number of Subjects Who Achieve Mucosal Healing at Week 52 | The endoscopic Mayo Score (Mayo endoscopic subscore) evaluates ulcerative colitis stage, based only on endoscopic exploration. The scale ranges from 0 to 3, with higher scores = more severe activity. Mucosal healing is defined as modified Mayo endoscopy sub-score (mMES) of 0 or 1. | 52 weeks | |
Secondary | Number of Subjects Who Achieve Clinical Improvement at Week 12 | The Mayo Clinic Score is comprised of 4 parts: stool frequency, rectal bleeding, endoscopic findings and physician's global assessment, each scored from 0-3. The total score ranges from 0-12 with higher scores indicating increased severity of disease. Improvement will be based on a reduction in the total Mayo Clinic score. | 12 weeks | |
Secondary | Change From Baseline in Total Mayo Scale Score at Week 52 | The Mayo Clinic Score is comprised of 4 parts: stool frequency, rectal bleeding, endoscopic findings and physician's global assessment, each scored from 0-3. The total score ranges from 0-12 with higher scores indicating increased severity of disease. Improvement was based on a reduction (mean change from Baseline [Week 0] to Week 52) in the total Mayo Clinic score. | 52 weeks | |
Secondary | Number of Subjects Who Achieve a Clinical Response at Week 12 | The Mayo Clinic Score is comprised of 4 parts: stool frequency, rectal bleeding, endoscopic findings and physician's global assessment, each scored from 0-3. The total score ranges from 0-12 with higher scores indicating increased severity of disease. Clinical Response is a reduction in the total Mayo Clinic score of at least 3 points. | 12 weeks | |
Secondary | Number of Subjects Who Achieve a Clinical Response at Week 52 | The Mayo Clinic Score is comprised of 4 parts: stool frequency, rectal bleeding, endoscopic findings and physician's global assessment, each scored from 0-3. The total score ranges from 0-12 with higher scores indicating increased severity of disease. Clinical Response indicates the change from Baseline in the Total Mayo Clinic score <= -3 and the percentage change from Baseline in the Total Mayo Clinic score <= -30% to Week 12, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of <= 1. | 52 weeks | |
Secondary | Number of Subjects Who Achieve Clinical Remission at Week 12 | The Mayo Clinic Score is comprised of 4 parts: stool frequency, rectal bleeding, endoscopic findings and physician's global assessment, each scored from 0-3. The total score ranges from 0-12 with higher scores indicating increased severity of disease. Clinical remission is defined as a total Mayo Clinic score of = 2 and no subscores > 1. | 12 weeks | |
Secondary | Number of Subjects Who Achieve Clinical Remission at Week 52 | The Mayo Clinic Score is comprised of 4 parts: stool frequency, rectal bleeding, endoscopic findings and physician's global assessment, each scored from 0-3. The total score ranges from 0-12 with higher scores indicating increased severity of disease. Clinical remission is defined as a total Mayo Clinic score of = 2 and no subscores > 1. | 52 weeks |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05702879 -
Combined Microbiota and Metabolic Signature in Ulcerative Colitis Predicts Anti-Inflammatory Therapy Success
|
||
Not yet recruiting |
NCT05953402 -
A Study of Ozanimod in Pregnant Women With Ulcerative Colitis and Their Offspring
|
||
Recruiting |
NCT05316584 -
A Novel Remote Patient and Medication Monitoring Solution to Improve Adherence and PerSiStence With IBD Therapy
|
N/A | |
Recruiting |
NCT03950232 -
An Extension Study for Treatment of Moderately to Severely Active Ulcerative Colitis
|
Phase 3 | |
Completed |
NCT03124121 -
Study of the Golimumab Exposure-Response Relationship Using Serum Trough Levels
|
Phase 4 | |
Not yet recruiting |
NCT06100289 -
A Study of Vedolizumab in Children and Teenagers With Ulcerative Colitis or Crohn's Disease
|
Phase 3 | |
Withdrawn |
NCT04209556 -
A Study To Evaluate The Safety And Efficacy Of PF-06826647 In Participants With Moderate To Severe Ulcerative Colitis
|
Phase 2 | |
Terminated |
NCT00061282 -
Clotrimazole Enemas for Pouchitis in Children and Adults
|
Phase 1/Phase 2 | |
Recruiting |
NCT04398550 -
SCD vs. Mediterranean Diet Therapy in Ulcerative Colitis
|
N/A | |
Recruiting |
NCT04314375 -
Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Budesonide Extended-release Tablets in Pediatric Subjects Aged 5 to 17 Years With Active, Mild to Moderate Ulcerative Colitis
|
Phase 4 | |
Active, not recruiting |
NCT04857112 -
Study Evaluating Efficacy and Safety of Amiselimod (MT-1303) in Mild to Moderate Ulcerative Colitis
|
Phase 2 | |
Completed |
NCT05051943 -
A Study of the Real-world Use of an Adalimumab Biosimilar and Evaluation of Nutritional Status on the Therapeutic Response
|
||
Active, not recruiting |
NCT04033445 -
A Study of Guselkumab in Participants With Moderately to Severely Active Ulcerative Colitis
|
Phase 2/Phase 3 | |
Recruiting |
NCT05428345 -
A Study of Vedolizumab SC Given to Adults With Moderate to Severe Ulcerative Colitis or Crohn's Disease in South Korea
|
||
Active, not recruiting |
NCT06221995 -
Energy Expenditure in Patients With Ulcerative Colitis Undergoing Surgery
|
||
Recruiting |
NCT04767984 -
Testing Atorvastatin to Lower Colon Cancer Risk in Longstanding Ulcerative Colitis
|
Phase 2 | |
Completed |
NCT02508012 -
Medico-economic Evaluation of the Therapeutic Drug Monitoring of Anti-TNF-α Agents in Inflammatory Bowel Diseases
|
N/A | |
Recruiting |
NCT06071312 -
FMT in Patients With Recurrent CDI and Ulcerative Colitis: Single Infusion Versus Sequential Approach
|
Phase 1/Phase 2 | |
Completed |
NCT03760003 -
Dose-Ranging Phase 2b Study of ABX464 in Moderate to Severe Ulcerative Colitis
|
Phase 2 | |
Not yet recruiting |
NCT05539625 -
Mini-MARVEL - Mitochondrial Antioxidant Therapy in Ulcerative Colitis
|
Phase 2 |