Clinical trial NCT03235752: Safety and Efficacy of TJ301 IV in Participants With Active Ulcerative Colitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Active Ulcerative Colitis
Keywords: Randomized
Double-blind
Placebo-controlled
Safety
Efficacy
Active Ulcerative Colitis
Lead sponsor: I-Mab Biopharma HongKong Limited
Sponsor class: INDUSTRY
First posted: 2017-08-01
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-blind, Placebo-controlled
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical and endoscopy response
timeFrame: Week 12
Secondary outcomes:
measure: Clinical and endoscopy remission at Week 12
timeFrame: Week 12.
measure: Clinical remission at Weeks 4, 6, 8, 10, and 12
timeFrame: Weeks 4, 6, 8, 10, and 12
Other outcomes:
measure: Change from Baseline to Weeks 4, 8, and 12 in exploratory biomarkers
timeFrame: Baseline to Weeks 4, 8, and 12
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital Affiliated to the Capital University of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: The Seventh Medical Center of PLA Army General Hospital
state: Beijing
city: Sichuan
country: China
facility: West China Hospital of Sichuan University
state: Chengdu
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-sen University
state: Guangzhou
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangzhou
city: Guangzhou
country: China
facility: Nanfang Hospital of SMU
state: Guangzhou
city: Guanzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangzhou
city: Hainan
country: China
facility: Hainan General Hospital
state: Hainan
city: Zhejiang
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University, School of Medicine
state: Hangzhou
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Harbin
city: Jilin
country: China
facility: The first Bethune hospital of Jilin university
state: Jilin
city: Nanchang
country: China
facility: The first affiliated hospital of Nanchang Univesity
state: Nanchang
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Nanjing
city: Nanjing
country: China
facility: The Affiliated Hospital of Nanjing University Medical School
state: Nanjing
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Nanjing
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Xin Hua Hospital affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shenyang
country: China
facility: Shengjing hospital of China medical university
state: Shenyang
city: Shanxi
country: China
facility: Second Hospital of Shanxi Medical University
state: Taiyuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Seoul
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
city: Kaohsiung
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Minhu Chen, Doctor
role: PRINCIPAL_INVESTIGATOR
References: