A Study to Evaluate the Efficacy and Safety of Hemay005 in the Treatment of Behçet Disease

A Phase Ⅱ Study to Evaluate the Efficacy and Safety of Hemay005 in the Treatment of Behçet Disease

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.

Study Overview

• Status: Terminated
• Conditions: Behçet Disease
• Intervention / Treatment: Drug: Hemay005; Drug: Hemay005; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • The First Affiliated Hospital of Bengbu Medical college
    • Hefei, Anhui, China
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China
      • Peking University First Hospital
    • Beijing, Beijing, China
      • Beijing Hospital
    • Beijing, Beijing, China
      • Peking University People's Hospital
    • Beijing, Beijing, China
      • Peking University Shougang Hospital
    • Beijing, Beijing, China
      • Xuanwu Hospital Capital Medical University
  • Fujian
    • Xiamen, Fujian, China
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen Memorial Hospital,Sun Yat-sen University
    • Shenzhen, Guangdong, China
      • The University of Hong Kong-Shenzhen Hospital
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
  • Hunan
    • Changsha, Hunan, China
      • The Second Xiangya Hospital of Central South University
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • The first affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Provincial Hospital
    • Suzhou, Jiangsu, China
      • The First Affiliated Hospital of Soochow University
    • Xuzhou, Jiangsu, China
      • The Affiliated Hospital of Xuzhou Medical University
  • Jiangxi
    • Jiujiang, Jiangxi, China
      • Jiu Jiang No.1 People's Hospital
    • Pingxiang, Jiangxi, China
      • Jiangxi Pingxiang People's Hospital
  • Jilin
    • Changchun, Jilin, China
      • Jilin Provincial People's Hospital
    • Changchun, Jilin, China
      • China-Japan Union Hospital of Jilin University
  • Shandong
    • Linyi, Shandong, China
      • Linyi People's Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Zhongshan Hospital affiliated to Fudan University
    • Shanghai, Shanghai, China
      • Renji Hospital, Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China
      • Huashan Hospital Affiliated to Fudan University
    • Shanghai, Shanghai, China
      • Tongji Hospital Of Tongji University Tang Jianping
  • Sichuan
    • Chengdu, Sichuan, China
      • The First Affiliated Hospital of Chengdu Medical College
  • Xinjiang
    • Ürümqi, Xinjiang, China
      • People's Hospital of Xinjiang Uygur Autonomous Region
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Provincial People's Hospital
    • Hangzhou, Zhejiang, China
      • First Affiliated Hospital,Zhejiang University School of Medicine
    • Wenzhou, Zhejiang, China
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hemay005 high dose group; 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.	Drug: Hemay005; Hemay005 tables 60mg bid p.o; Other Names: Phosphodiesterase 4 (PDE4) inhibitors; Drug: Hemay005; Hemay005 tables 45mg bid p.o; Other Names: Phosphodiesterase 4 (PDE4) inhibitors
Experimental: Hemay005 lower dose group; 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.	Drug: Hemay005; Hemay005 tables 60mg bid p.o; Other Names: Phosphodiesterase 4 (PDE4) inhibitors; Drug: Hemay005; Hemay005 tables 45mg bid p.o; Other Names: Phosphodiesterase 4 (PDE4) inhibitors
Placebo Comparator: 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.	Drug: Hemay005; Hemay005 tables 60mg bid p.o; Other Names: Phosphodiesterase 4 (PDE4) inhibitors; Drug: Hemay005; Hemay005 tables 45mg bid p.o; Other Names: Phosphodiesterase 4 (PDE4) inhibitors; Other: Placebo; placebo to Hemay005 tables bid p.o

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to evaluate the efficacy of Hemay005 in the treatment of Behçet's disease.	Area under the curve (AUC) for the number of oral ulcers from baseline through Week 12	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving an oral ulcer complete response	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	week 6
Complete response rate for oral ulcers	Complete response rate for oral ulcers at day 3, day 7 and Week 12	day 3, day 7 and week12
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)	Change from baseline in the pain of oral ulcers as measured by VAS at Week 12	week12
change of the number of oral ulcers	Change from baseline in the number of oral ulcers at Week 12	week12
Time to oral ulcer resolution	Time to oral ulcer resolution (complete response) that the first instance when a subject has a complete response during the core-Treatment Phase	week12
Proportion of subjects achieving an oral ulcer complete response in the core-treatment phase	Proportion of subjects achieving an oral ulcer complete response (oral ulcer-free) and who remain oral ulcer free during the core-treatment Phase	week12
Number of oral ulcers who has a reappearance during the core-treatment phase	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	week12
Time to oral ulcer reappearance during the core-treatment	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	week12
change of the total score of Physician's Global Assessment(PGA)	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	week12
change of BD Current Activity Form(BDCAF)	change from baseline in the total score of the BDCAF questionnaire at week 12	week12
change of Multi-Dimensional Health Assessment Questionnaire (MDHAQ)	change from baseline in the total score of the MDHAQ questionnaire at week 12	week12
change of short from health survey(SF-36)	change from baseline in the total score of the SF-36 questionnaire at week 12	week12
Complete response rate for genital ulcers	Complete response rate for genital ulcers at Week 12 for subjects who had genital ulcers at Baseline	week12
change of the pain evaluation of genital ulcers	Change from baseline in the pain of genital ulcers as measured by VAS at Week 12	week12
Change of the Behçet's syndrome activity score(BSAS) score	Change from Baseline in BSAS score at Week 12	week12
Maximum Plasma Concentration (Cmax)	the population pharmacokinetic (popPK) characteristics Cmax of Hemay005 in BD patients	week24
Minimum Plasma Concentration (Cmin)	the population pharmacokinetic (popPK) characteristics Cmin of Hemay005 in BD patients	week24
Time to peak (Tmax)	the population pharmacokinetic (popPK) characteristics Tmax of Hemay005 in BD patients	week24
Elimination half-life (T1/2)	the population pharmacokinetic (popPK) characteristics T1/2 of Hemay005 in BD patients	week24
Area under drug time curve (AUC)	the population pharmacokinetic (popPK) characteristics AUC of Hemay005 in BD patients	week24
Clearance (Cl)	the population pharmacokinetic (popPK) characteristics Cl of Hemay005 in BD patients	week24
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])	the Incidence of Treatment-Emergent Adverse Events of Hemay005 in BD patients with different dosing group	week24
the number of subjects who terminated hemay005 prematurely due to adverse events (AE) [Safety and Tolerability])	the number of subjects who terminated hemay005 prematurely due to adverse events (AE) in BD patients with different dosing group	week24

Collaborators and Investigators

• Sponsor: Tianjin Hemay Pharmaceutical Co., Ltd
• Investigators: Principal Investigator: Zhanguo Li, Doctor, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Actual): April 30, 2022
• Study Completion (Actual): April 30, 2022

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 25, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 15, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Behçet Disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Eye Diseases; Genetic Diseases, Inborn; Stomatognathic Diseases; Mouth Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Vasculitis; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Behcet Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dermatologic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Hemay005
• Other Study ID Numbers: HM005BD2S01

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