Safety and Efficacy of TJ301 IV in Participants With Active Ulcerative Colitis

NCT ID: NCT03235752

Last Updated: 2021-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-06
• Study Completion Date: 2020-12-21

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled phase II study.

Detailed Description

is a multicenter, randomized, double-blind, placebo-controlled phase II study. The trial includes a Run-in Period (if stable conventional treatment needed), a 4-week Screening Period, a 12-week Treatment Period, and a 3-week Safety Follow-up Period to Day 105.

90 patients will be centrally, dynamically, randomly assigned to 3 groups (1:1:1) to receive 600mg TJ301 Q2W, 300mg TJ301 Q2W or placebo Q2W.

Conditions

Active Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TJ301 300mg

TJ301 300mg administrations will occur on Days 0, 14, 28, 42, 56, and 70.

Group Type: EXPERIMENTAL

TJ301 300mg

Intervention Type: DRUG

TJ301 300mg IV infusion

TJ301 600mg

TJ301 300mg administrations will occur on Days 0, 14, 28, 42, 56, and 70.

Group Type: EXPERIMENTAL

TJ301 600mg

Intervention Type: DRUG

TJ301 600mg IV infusion

Placebo

Placebo administrations will occur on Days 0, 14, 28, 42, 56, and 70.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo IV infusion

Interventions

TJ301 300mg

TJ301 300mg IV infusion

Intervention Type: DRUG

TJ301 600mg

TJ301 600mg IV infusion

Intervention Type: DRUG

Placebo

Placebo IV infusion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male and female patients 18-70 (inclusive) years of age.

2. Hisory of active UC of more than 3 months. Active UC confirmed by colonoscopy with biopsy or flexible sigmoidoscopy with biopsy at Screening, with extending > 15-cm past the anal verge from endoscopy. Biopsy sample is not necessary if UC is already confirmed.

3. Active UC with a full Mayo score≥5 and a rectal bleeding subscore ≥1 at screening.

4. During Day -28 to Day -6 prior to Randomisation, an endoscopy subscore ≥2.

5. Treated with conventional non-biological UC therapy: with corticosteroids stable for at least 2 weeks prior to Randomization at no more than 20 mg prednisone per day (or equivalent), and/or with medications containing 5-aminosalicylates (5-ASA) at no less than 2 g 5-ASA per day for at least 3 months and stable for at least 4 weeks prior to Randomization, and/or with azathioprine (AZA) at no less than 0.75 mg/kg/day or mercaptopurine (6-MP) at no less than 0.5 mg/kg/day for at least 6 months and stable for at least 6 weeks prior to Randomization, or MTX no less than 12.5 mg/week and stable for at least 12 weeks prior to Randomization.

6. Male subjects and female subjects of child bearing potential must have been willing to practice effective contraception during the study and been willing and able to continue contraception for 1 month after their last dose of the study treatment.

7. The patient is able and willing to comply with the requirements of this trial protocol.

8. The subject should be able to read and write to understand and fill out Patient Diary.

9. Voluntarily signed Informed Consent obtained before any trial-related procedures are performed.

10. The subject have not received any biologic therapies OR have received 1 biologic drug for the treatment of UC or immune diseases and the last dose must be longer than 8-week or a 5 half-life (whichever is longer) period prior to the first dose of study drug.

Exclusion Criteria

1. Pregnant or breastfeeding women.

2. Contraindication to colonoscopy or sigmoidoscopy.

3. Allergies to any component of TJ301.

4. Subject who is likely to receive surgery for UC treatment within 1 month based on investigator's evaluation.

5. History of colostomy, colectomy or partial colectomy.

6. Current diagnosis of inflammatory bowel disease unclassified, Crohn's disease, ischemic colitis, fulminant colitis and/or toxic megacolon, patients with ulcerative colitis limited to the rectum (ulcerative proctitis), infective enteritis, amebic bowel disease or intestinal schistosomiasis.

7. History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix. If the Screening colonoscopy shows evidence of dysplasia or a malignancy, the patient is not eligible.

8. Primary or secondary immunodeficiency including neutropenia (absolute neutrophil count <1500/μL); or lymphopenia (absolute lymphocyte count <500/μL).

9. Moderate to severe anaemia (haemoglobin <9 g/dL), or thrombocytopenia (platelet count <75 000/μL), or serum creatinine >2 mg/dL.

10. Autoimmune disease besides UC, with the exceptions of Sjogren's syndrome or hypothyroidism.

11. Clostridium (C.) difficile positive at screening visit or treated for C. difficile within the 4 weeks prior to Randomization.

12. serum transaminases >2.5 x upper limit of normal [ULN], alkaline phosphatase >2.5 x ULN.

13. Serious underlying disease other than UC in the opinion of the investigator.

14. History of drug addiction within the last 1 year or current drug addiction or use of illicit drugs.

15. Any indication of the regular use of more than 40 grams of alcohol every day.

16. Smokers who smoke more than 10 cigarettes per day.

17. Known concurrent acute or chronic viral hepatitis B or C infection or human immunodeficiency virus (HIV) infection.

18. Presence or history of active tuberculosis (TB) or latent TB infection, defined as 1) a positive QuantiFERON-TB Gold test at Screening; or 2) a T-spot test within 4 weeks of Randomisation and evidence of current or previous pulmonary tuberculosis by low-dose CT or chest X-ray within 12 weeks of Randomisation. Patients with old TB will also be excluded.

19. Positive immunoglobulin M antibody titres to Epstein-Barr virus (EBV).

20. Subjects with positive results for cytomegalovirus at screening are to be excluded.

21. Receiving any investigational therapy or any approved therapy for investigational use within 30 days or 5 half-lives prior to Randomization (whichever is longer).

22. Currently taking any medications other than those allowed per protocol guidelines.

23. Infections (including diverticulitis) requiring treatment with antibiotics, antivirals, or antifungals within 14 days prior to Randomisation.

24. Received any live (attenuated) vaccines within 30 days prior to Randomisation.

25. Recent treatment with medium-to-high-dose intravenous corticosteroids (methylprednisolone 60 mg/day or hydrocortisone 300 mg/day) within 8 weeks prior to Randomisation or oral corticosteroids of more than 20 mg prednisone per day (or equivalent).

26. Receipt of cyclosporine, tacrolimus, sirolimus, thalidomide, or mycophenolate mofetil within 30 days prior to Randomisation.

27. Treatment with therapeutic enema or suppository, other than required for endoscopy preparation, within 14 days prior to the screening endoscopy and during the remainder of the trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

I-Mab Biopharma HongKong Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Minhu Chen, Doctor

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital, Sun Yat-Sen University

Locations

Peking University First Hospital

Beijing, Beijing Municipality, China

Beijing Friendship Hospital Affiliated to the Capital University of Medical Sciences

Beijing, Beijing Municipality, China

The Seventh Medical Center of PLA Army General Hospital

Beijing, Beijing Municipality, China

West China Hospital of Sichuan University

Sichuan, Chengdu, China

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangzhou, China

Guangdong Provincial People's Hospital

Guangzhou, Guangzhou, China

Nanfang Hospital of SMU

Guangzhou, Guangzhou, China

The First Affiliated Hospital, Sun Yat-sen University

Guanzhou, Guangzhou, China

Hainan General Hospital

Hainan, Hainan, China

Sir Run Run Shaw Hospital Zhejiang University, School of Medicine

Zhejiang, Hangzhou, China

The First Affiliated Hospital of Harbin Medical University

Harbin, Harbin, China

The first Bethune hospital of Jilin university

Jilin, Jilin, China

The first affiliated hospital of Nanchang Univesity

Nanchang, Nanchang, China

Jiangsu Province Hospital

Nanjing, Nanjing, China

The Affiliated Hospital of Nanjing University Medical School

Nanjing, Nanjing, China

Zhongda Hospital Southeast University

Nanjing, Nanjing, China

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Xin Hua Hospital affiliated to Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Shengjing hospital of China medical university

Shenyang, Shenyang, China

Second Hospital of Shanxi Medical University

Shanxi, Taiyuan, China

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, China

Yeungnam University Medical Center

Daegu, , South Korea

CHA Bundang Medical Center, CHA University

Seoul, , South Korea

National Taiwan University Hospital

Kaohsiung City, , Taiwan

Chang Gung Memorial Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Countries

China; South Korea; Taiwan

References

Zhang S, Chen B, Wang B, Chen H, Li Y, Cao Q, Zhong J, Shieh MJ, Ran Z, Tang T, Yang M, Xu B, Wang Q, Liu Y, Ma L, Wang X, Zhang N, Zhang S, Guo W, Huang L, Schreiber S, Chen M. Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis: A Randomized Clinical Trial. JAMA. 2023 Mar 7;329(9):725-734. doi: 10.1001/jama.2023.1084.

Reference Type: DERIVED

PMID: 36881032 (View on PubMed)

Other Identifiers

CTJ301UC201

Identifier Type: -

Identifier Source: org_study_id