A Study to Evaluate the Efficacy and Safety of Hemay005 in the Treatment of Behçet Disease
- Registration Number
- NCT04609397
- Lead Sponsor
- Tianjin Hemay Pharmaceutical Co., Ltd
- Brief Summary
This is a phase 2, multi-center, randomized, placebo-controlled, double-blind, parallel-group study with an equal randomization among the Hemay005 high dose, lower dose and placebo treatment groups. After subject randomization, each subject will enter an core-treatment Phase for 12 weeks following an extended-treatment phase for another 12weeks and a follow up phase for 4weeks.
- Detailed Description
this study is a phase 2, multi-center, randomized, placebo-controlled, double-blind, parallel-group study to evaluate Hemay005 efficacy and safety of the treatment of patients with Behçet Disease(BD). Around 252 subjects will be randomized into this study.
The whole study will including 4 phases that a screening phase, core-treatment phase(12weeks), extended-treatment phase (12weeks) and follow-up phase(4 weeks).
Screening: All subjects will undergo a screening period of up to 6 weeks prior to baseline visit (visit 2, day of randomization, Day0).
Core treatment phase: eligible BD patients will randomly assigned to Hemay005 high-dose group, Hemay005 low-dose group, placebo (core treatment phase) + Hemay005 high-dose group (extended treatment phase), or placebo (core treatment phase) + Hemay005 low-dose group (extended treatment phase). During the core-treatment period, hemay005 will be administered twice daily for 12 weeks. The randomization was stratified to minimize the imbalance between treatment groups.
Extended treatment phase: Subjects in the high-dose and low-dose groups during the extended treatment period will still given the dose of core-treatment phase for 12 weeks. Subjects who received placebo during the core treatment will assigned to either a high-dose group or a low-dose group according the allocation at visit 2 until 12 weeks after. During this period, the subject and investigator are remain blind at this stage.
Follow up phase: Subjects in the study (also including those who withdraw from treatment for any reason) will have another follow up for 4 weeks after the end of the last administration.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 89
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1.Understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.
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2.Male and female subjects 18~75(inclusive) years of age at the time of signing the informed consent form.
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3.Diagnosed with Behçet's disease meeting the International Study Group (ISG) criteria (2013).
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4.Subjects must have at least 2 oral ulcers at V1, and:
- at least 2 oral ulcers at V2 if V2 occurs at least 14 days after Visit 1, OR
- at least 3 oral ulcers at V2 if V2 occurs at least 0~42 days after Visit 1.
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- According to the site investigator judgement, subject is suitable to the systemic but not topical treatment of oral ulcer considering the severity and affected area of the disease OR the oral ulcer cannot be well controlled by topical treatment and have to take the systemic treatment.
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6.All females of childbearing potential (FCBP) and male subjects who did not receive the vasectomy must take effective contraceptive measures.
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1.subject has the BD related major organ activity lesions requiring immunosuppressive therapy- pulmonary, vascular, gastrointestinal, and central nervous systems (eg, meningoencephalitis) manifestations, etc. However:
- Previous major organ involvement is allowed if it occurred at least one years prior to screening visit and is not active at time of enrollment.
- Subjects with BD-related arthritis and BD-skin manifestations are also allowed
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- Any clinically significant heart disease (e.g., but not limited to unstable ischemic heart disease, New York Heart Association(NYHA) class III / IV left ventricular failure, or myocardial infarction) or clinically significant 12 lead ECG abnormalities found during screening, which, according to the investigator's judgment, may put the patient at safety risk or may interfere with the investigator;
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subjects who current receiving immunotherapy including:
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7 days prior to Visit 2 (randomization) for colchicine.
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10 days prior to Visit 2 (randomization) for azathioprine, mycophenolate mofetil, baricitinib or Tofacitinib.
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4 weeks prior to visit 2(randomization) for cyclosporin, methotrexate, cyclophosphamide, thalidomide, and dapsone.
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At least 5 terminal half-lives for all biologics, including,within:
- Four weeks prior to visit 2(randomization) for etanercept.
- Eight weeks prior to visit 2(randomization) for infliximab.
- Ten weeks prior to visit 2(randomization) for adalimumab, golimumab, abatacept, and tocilizumab.
- Six months prior to visit 2(randomization) for secukinumab.
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4.Having received intra-articular or parenteral corticosteroids within 6 weeks (42 days) prior to Visit 2.
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5.Laboratory examination of V1 in screening period:
- Hemoglobin ≤ 85g / L;
- The white blood cell (WBC) count was less than 3.0 × 10^9 / L or more than 14 × 10^9 / L;
- Platelet < 100 × 10^9 / L;
- Serum creatinine > 1.5mg/dl (> 132.6 μ mol / L);
- Total bilirubin > 2.0 mg / dl (> 34.2 μ mol / L);
- The Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) were higher than 1.5 times of the upper limit of normal value.
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6.subjects who received strong cytochrome P450 enzyme inducer within 4 weeks prior to visit2.
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7.Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C and herpes zoster, histoplasmosis, coccidiomycosis, but excluding onychomycosis) , judged by investigator,may put the patient at safety risk.
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8.Clinically significant abnormality on chest radiograph or CT,judged by investigator, may put the patient at safety risk.
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9.History of transplantation and immunodeficiency disease, including those subject has a positive test for human immunodeficiency virus (HIV).
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10.subject who use of any investigational products of clinical trials within 4 weeks or within 5 pharmacokinetic/pharmacodynamic half-lives prior to randomization, whichever is longer;
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11.known to be allergic or allergic to the investigational products or ingredients;
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12.History of alcohol or drug abuse, or a history of mental illness;
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13.Subjects with severe, progressive, or uncontrolled disease, judged by the investigator, who maybe at risk if participate this study or those subjects whose participation may influence the interpretation of study results.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo In Core-treatment period, subject will take placebo for 12 weeks, and in the following extend-treatment period, subject will take Hemay005 60mg or hemay005 45mg twice daily according to pre-allocation at randomization visit for 12 weeks. Hemay005 high dose group Hemay005 In Core-treatment period, subject will take Hemay005 60mg twice daily for 12 weeks, and in the following extend-treatment period, subject will take Hemay005 60mg twice daily for 12 weeks. Placebo Hemay005 In Core-treatment period, subject will take placebo for 12 weeks, and in the following extend-treatment period, subject will take Hemay005 60mg or hemay005 45mg twice daily according to pre-allocation at randomization visit for 12 weeks. Hemay005 lower dose group Hemay005 In Core-treatment period, subject will take Hemay005 45mg twice daily for 12 weeks, and in the following extend-treatment period, subject will take Hemay005 45mg twice daily for 12 weeks.
- Primary Outcome Measures
Name Time Method to evaluate the efficacy of Hemay005 in the treatment of Behçet's disease. week 12 Area under the curve (AUC) for the number of oral ulcers from baseline through Week 12
- Secondary Outcome Measures
Name Time Method Complete response rate for oral ulcers day 3, day 7 and week12 Complete response rate for oral ulcers at day 3, day 7 and Week 12
change of the number of oral ulcers week12 Change from baseline in the number of oral ulcers at Week 12
Proportion of subjects achieving an oral ulcer complete response week 6 Proportion of subjects achieving an oral ulcer complete response (oral ulcer-free) by Week 6 after dosing, and who remain oral ulcer free for at least 6 additional weeks during the Treatment Phase
change of the pain evaluation of oral ulcers as measured by Visual analogue scale(VAS)(From 0-100, the higher score means the worse outcome) week12 Change from baseline in the pain of oral ulcers as measured by VAS at Week 12
Proportion of subjects achieving an oral ulcer complete response in the core-treatment phase week12 Proportion of subjects achieving an oral ulcer complete response (oral ulcer-free) and who remain oral ulcer free during the core-treatment Phase
Number of oral ulcers who has a reappearance during the core-treatment phase week12 Number of oral ulcers following loss of complete response that the first instance when a subject has a reappearance of oral ulcers following a complete response during the core-Treatment Phase
change of the total score of Physician's Global Assessment(PGA) week12 change from baseline in the total score of the PGA of skin lesions of BD at week 12 in those subjects who had at baseline
change of Multi-Dimensional Health Assessment Questionnaire (MDHAQ) week12 change from baseline in the total score of the MDHAQ questionnaire at week 12
change of the pain evaluation of genital ulcers week12 Change from baseline in the pain of genital ulcers as measured by VAS at Week 12
Area under drug time curve (AUC) week24 the population pharmacokinetic (popPK) characteristics AUC of Hemay005 in BD patients
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) week24 the Incidence of Treatment-Emergent Adverse Events of Hemay005 in BD patients with different dosing group
Time to peak (Tmax) week24 the population pharmacokinetic (popPK) characteristics Tmax of Hemay005 in BD patients
Maximum Plasma Concentration (Cmax) week24 the population pharmacokinetic (popPK) characteristics Cmax of Hemay005 in BD patients
Minimum Plasma Concentration (Cmin) week24 the population pharmacokinetic (popPK) characteristics Cmin of Hemay005 in BD patients
Elimination half-life (T1/2) week24 the population pharmacokinetic (popPK) characteristics T1/2 of Hemay005 in BD patients
Clearance (Cl) week24 the population pharmacokinetic (popPK) characteristics Cl of Hemay005 in BD patients
Time to oral ulcer resolution week12 Time to oral ulcer resolution (complete response) that the first instance when a subject has a complete response during the core-Treatment Phase
Time to oral ulcer reappearance during the core-treatment week12 Time to recurrence of oral ulcers following loss of complete response that the first instance when a subject has a reappearance of oral ulcers following a complete response during the core-Treatment Phase
change of short from health survey(SF-36) week12 change from baseline in the total score of the SF-36 questionnaire at week 12
Change of the Behçet's syndrome activity score(BSAS) score week12 Change from Baseline in BSAS score at Week 12
the number of subjects who terminated hemay005 prematurely due to adverse events (AE) [Safety and Tolerability]) week24 the number of subjects who terminated hemay005 prematurely due to adverse events (AE) in BD patients with different dosing group
change of BD Current Activity Form(BDCAF) week12 change from baseline in the total score of the BDCAF questionnaire at week 12
Complete response rate for genital ulcers week12 Complete response rate for genital ulcers at Week 12 for subjects who had genital ulcers at Baseline
Trial Locations
- Locations (31)
Peking University Shougang Hospital
🇨🇳Beijing, Beijing, China
Xuanwu Hospital Capital Medical University
🇨🇳Beijing, Beijing, China
Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of science and technology
🇨🇳Baotou, Inner Mongolia, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Jiangsu Provincial Hospital
🇨🇳Nanjing, Jiangsu, China
The Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
Jiu Jiang NO.1 people's Hospital
🇨🇳Jiujiang, Jiangxi, China
China-Japan Union Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Jiangxi Pingxiang people's Hospital
🇨🇳Pingxiang, Jiangxi, China
Jilin Provincial People's Hospital
🇨🇳Changchun, Jilin, China
Linyi people's Hospital
🇨🇳Linyi, Shandong, China
Huashan Hospital Affiliated to Fudan University
🇨🇳Shanghai, Shanghai, China
Renji Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Zhongshan Hospital Affiliated to Fudan University
🇨🇳Shanghai, Shanghai, China
People's Hospital of Xinjiang Uygur Autonomous Region
🇨🇳Ürümqi, Xinjiang, China
Tongji Hospital Of Tongji University Tang Jianping
🇨🇳Shanghai, Shanghai, China
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, Anhui, China
Anhui provincial hospital
🇨🇳Hefei, Anhui, China
Beijing hospital
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
The University of Hong Kong-Shenzhen Hospital
🇨🇳Shenzhen, Guangdong, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Peking University People's Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Chengdu Medical College
🇨🇳Chengdu, Sichuan, China
First Affiliated Hospital，Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Zhejiang Provincial People's Hospital
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China