Clinical trial NCT04609397: A Study to Evaluate the Efficacy and Safety of Hemay005 in the Treatment of Behçet Disease
Official title: A Phase Ⅱ Study to Evaluate the Efficacy and Safety of Hemay005 in the Treatment of Behçet Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Behçet Disease
Keywords: Behçet Disease
Lead sponsor: Ganzhou Hemay Pharmaceutical Co., Ltd
Sponsor class: INDUSTRY
First posted: 2020-10-30
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

* 1.Understand and voluntarily sign an informed consent form prior to any study related assessments/procedures being conducted.
* 2.Male and female subjects 18\~75(inclusive) years of age at the time of signing the informed consent form.
* 3.Diagnosed with Behçet's disease meeting the International Study Group (ISG) criteria (2013).
* 4.Subjects must have at least 2 oral ulcers at V1, and:

  1. at least 2 oral ulcers at V2 if V2 occurs at least 14 days after Visit 1, OR
  2. at least 3 oral ulcers at V2 if V2 occurs at least 0\~42 days after Visit 1.
* 5. 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.
* 6.All females of childbearing potential (FCBP) and male subjects who did not receive the vasectomy must take effective contraceptive measures.

Exclusion Criteria:

* 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:

  1. 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.
  2. Subjects with BD-related arthritis and BD-skin manifestations are also allowed
* 2. 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;
* 3. subjects who current receiving immunotherapy including:

  1. 7 days prior to Visit 2 (randomization) for colchicine.
  2. 10 days prior to Visit 2 (randomization) for azathioprine, mycophenolate mofetil, baricitinib or Tofacitinib.
  3. 4 weeks prior to visit 2(randomization) for cyclosporin, methotrexate, cyclophosphamide, thalidomide, and dapsone.
  4. At least 5 terminal half-lives for all biologics, including,within:

     1. Four weeks prior to visit 2(randomization) for etanercept.
     2. Eight weeks prior to visit 2(randomization) for infliximab.
     3. Ten weeks prior to visit 2(randomization) for adalimumab, golimumab, abatacept, and tocilizumab.
     4. Six months prior to visit 2(randomization) for secukinumab.
* 4.Having received intra-articular or parenteral corticosteroids within 6 weeks (42 days) prior to Visit 2.
* 5.Laboratory examination of V1 in screening period:

  1. Hemoglobin ≤ 85g / L;
  2. The white blood cell (WBC) count was less than 3.0 × 10\^9 / L or more than 14 × 10\^9 / L;
  3. Platelet \< 100 × 10\^9 / L;
  4. Serum creatinine \> 1.5mg/dl (\> 132.6 μ mol / L);
  5. Total bilirubin \> 2.0 mg / dl (\> 34.2 μ mol / L);
  6. The Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) were higher than 1.5 times of the upper limit of normal value.
* 6.subjects who received strong cytochrome P450 enzyme inducer within 4 weeks prior to visit2.
* 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.
* 8.Clinically significant abnormality on chest radiograph or CT,judged by investigator, may put the patient at safety risk.
* 9.History of transplantation and immunodeficiency disease, including those subject has a positive test for human immunodeficiency virus (HIV).
* 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;
* 11.known to be allergic or allergic to the investigational products or ingredients;
* 12.History of alcohol or drug abuse, or a history of mental illness;
* 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.

Primary outcomes:
measure: to evaluate the efficacy of Hemay005 in the treatment of Behçet's disease.
timeFrame: week 12
Secondary outcomes:
measure: Proportion of subjects achieving an oral ulcer complete response
timeFrame: week 6
measure: Complete response rate for oral ulcers
timeFrame: day 3, day 7 and week12
measure: 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)
timeFrame: week12
measure: change of the number of oral ulcers
timeFrame: week12
measure: Time to oral ulcer resolution
timeFrame: week12
measure: Proportion of subjects achieving an oral ulcer complete response in the core-treatment phase
timeFrame: week12
measure: Number of oral ulcers who has a reappearance during the core-treatment phase
timeFrame: week12
measure: Time to oral ulcer reappearance during the core-treatment
timeFrame: week12
measure: change of the total score of Physician's Global Assessment(PGA)
timeFrame: week12
measure: change of BD Current Activity Form(BDCAF)
timeFrame: week12
measure: change of Multi-Dimensional Health Assessment Questionnaire (MDHAQ)
timeFrame: week12
measure: change of short from health survey(SF-36)
timeFrame: week12
measure: Complete response rate for genital ulcers
timeFrame: week12
measure: change of the pain evaluation of genital ulcers
timeFrame: week12
measure: Change of the Behçet's syndrome activity score(BSAS) score
timeFrame: week12
measure: Maximum Plasma Concentration (Cmax)
timeFrame: week24
measure: Minimum Plasma Concentration (Cmin)
timeFrame: week24
measure: Time to peak (Tmax)
timeFrame: week24
measure: Elimination half-life (T1/2)
timeFrame: week24
measure: Area under drug time curve (AUC)
timeFrame: week24
measure: Clearance (Cl)
timeFrame: week24
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])
timeFrame: week24
measure: the number of subjects who terminated hemay005 prematurely due to adverse events (AE) [Safety and Tolerability])
timeFrame: week24
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: Anhui provincial hospital
state: Anhui
city: Beijing
country: China
facility: Beijing hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Shougang Hospital
state: Beijing
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
state: Beijing
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University
state: Guangdong
city: Shenzhen
country: China
facility: The University of Hong Kong-Shenzhen Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of science and technology
state: Inner Mongolia
city: Nanjing
country: China
facility: Jiangsu Provincial Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Jiujiang
country: China
facility: Jiu Jiang NO.1 people's Hospital
state: Jiangxi
city: Pingxiang
country: China
facility: Jiangxi Pingxiang people's Hospital
state: Jiangxi
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Jilin Provincial People's Hospital
state: Jilin
city: Linyi
country: China
facility: Linyi people's Hospital
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital Affiliated to Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Tongji Hospital Of Tongji University Tang Jianping
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
state: Shanghai
city: Chengdu
country: China
facility: The First Affiliated Hospital of Chengdu Medical College
state: Sichuan
city: Ürümqi
country: China
facility: People's Hospital of Xinjiang Uygur Autonomous Region
state: Xinjiang
city: Hangzhou
country: China
facility: First Affiliated Hospital，Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Peking University People's Hospital
name: zhanguo Li, Doctor
role: PRINCIPAL_INVESTIGATOR
References: