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

A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of TJ301 (FE 999301) Administered Intravenously in Patients With Active Ulcerative Colitis

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

Study Overview

• Status: Completed
• Conditions: Active Ulcerative Colitis
• Intervention / Treatment: Drug: TJ301 300mg; Drug: TJ301 600mg; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China
      • Beijing Friendship Hospital Affiliated to the Capital University of Medical Sciences
    • Beijing, Beijing, China
      • The Seventh Medical Center of PLA Army General Hospital
  • Chengdu
    • Sichuan, Chengdu, China, 610000
      • West China Hospital of Sichuan University
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510655
      • The Sixth Affiliated Hospital of Sun Yat-Sen University
    • Guangzhou, Guangzhou, China
      • Guangdong Provincial People's Hospital
    • Guangzhou, Guangzhou, China
      • Nanfang Hospital of SMU
    • Guanzhou, Guangzhou, China, 510080
      • The First Affiliated Hospital, Sun Yat-sen University
  • Hainan
    • Hainan, Hainan, China
      • Hainan General Hospital
  • Hangzhou
    • Zhejiang, Hangzhou, China
      • Sir Run Run Shaw Hospital Zhejiang University, School of Medicine
  • Harbin
    • Harbin, Harbin, China
      • The First Affiliated Hospital of Harbin Medical University
  • Jilin
    • Jilin, Jilin, China
      • The First Bethune Hospital of Jilin University
  • Nanchang
    • Nanchang, Nanchang, China
      • The first affiliated hospital of Nanchang Univesity
  • Nanjing
    • Nanjing, Nanjing, China
      • Jiangsu Province Hospital
    • Nanjing, Nanjing, China
      • The Affiliated Hospital of Nanjing University Medical School
    • Nanjing, Nanjing, China
      • Zhongda Hospital Southeast University
  • Shanghai
    • Shanghai, Shanghai, China
      • Renji Hospital, Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China
      • Xin Hua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
  • Shenyang
    • Shenyang, Shenyang, China
      • Shengjing Hospital of China Medical University
  • Taiyuan
    • Shanxi, Taiyuan, China
      • Second Hospital of Shanxi Medical University
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University General Hospital
• Korea, Republic of
  • Daegu, Korea, Republic of
    • Yeungnam University Medical Center
  • Seoul, Korea, Republic of
    • CHA Bundang Medical Center, CHA University
• Taiwan
  • Kaohsiung, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Chang Gung Memorial Hospital
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TJ301 300mg; TJ301 300mg administrations will occur on Days 0, 14, 28, 42, 56, and 70.	Drug: TJ301 300mg; TJ301 300mg IV infusion
Experimental: TJ301 600mg; TJ301 300mg administrations will occur on Days 0, 14, 28, 42, 56, and 70.	Drug: TJ301 600mg; TJ301 600mg IV infusion
Placebo Comparator: Placebo; Placebo administrations will occur on Days 0, 14, 28, 42, 56, and 70.	Drug: Placebo; Placebo IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical and endoscopy response	Clinical and endoscopy response (decrease from Baseline in full Mayo score ≥3 and ≥30%, including decrease from Baseline in rectal bleeding subscore ≥1 or rectal bleeding subscore ≤1) at Week 12.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical and endoscopy remission at Week 12	Clinical and endoscopy remission at Week 12, defined as a full Mayo score ≤2, no individual subscore >1, rectal bleeding subscore = 0.	Week 12.
Clinical remission at Weeks 4, 6, 8, 10, and 12	Clinical remission at Weeks 4, 6, 8, 10, and 12 defined as a stool frequency subscore=0, rectal bleeding subscore = 0, and 9-point partial Mayo score ≤1.	Weeks 4, 6, 8, 10, and 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Weeks 4, 8, and 12 in exploratory biomarkers	Change from Baseline to Weeks 4, 8, and 12 in exploratory biomarkers (erythrocyte sedimentation rate [ESR], C-reactive protein (CRP), IL-6, IL-6/sIL-6R complex, neutrophil and platelet count, faecal calprotectin).	Baseline to Weeks 4, 8, and 12

Collaborators and Investigators

• Sponsor: I-Mab Biopharma HongKong Limited
• Investigators: Principal Investigator: Minhu Chen, Doctor, First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2018
• Primary Completion (Actual): December 21, 2020
• Study Completion (Actual): December 21, 2020

Study Registration Dates

• First Submitted: July 28, 2017
• First Submitted That Met QC Criteria: July 28, 2017
• First Posted (Actual): August 1, 2017

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: January 3, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Placebo-controlled; Randomized; Double-blind; Active Ulcerative Colitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: CTJ301UC201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No