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.

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.

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.