A Phase III Clinical Study of Efficacy and Safety of Hemay005 Tablets in Patients With Behçet's Disease
Overview
- Phase
- Phase 3
- Intervention
- Hemay005
- Conditions
- Behçet's Disease
- Sponsor
- Ganzhou Hemay Pharmaceutical Co., Ltd
- Enrollment
- 162
- Locations
- 22
- Primary Endpoint
- Efficacy assessed by oral ulcers
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a phase 3, 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 40 weeks and a follow up phase for 4weeks.
Detailed Description
This is a multi-center, randomized, double-blind, placebo-parallel controlled phase III clinical study. The study consists of four phases, namely the screening period, the core treatment period, the extension period, and the drug discontinuation observation period. Screening period: All subjects will undergo a screening period for up to 8 weeks prior to the baseline visit (V2, randomization day, Day 0). Core treatment period: Patients with Behçet's disease (BD) meeting the eligibility criteria upon screening will be randomized in a 1:1: 1 ratio to the Hemay005 Tablets 45 mg BID test group, Hemay005 Tablets 60 mg BID test group, or the placebo group. They will first be given escalating doses for 7 days; subsequently starting from Day 7, they will be given Hemay005 Tablets 45 mg BID or 60 mg BID or the placebo BID continuously until Week 12. Extension period: Considering benefits for subjects in the placebo group, and to observe the efficacy and safety of long-term treatment, all subjects will enter a 40-week extension period at the end of the core treatment period. Subjects enrolled in the test groups for the core treatment period will continue treatment at the dose for the core treatment period for 40 weeks during the extension period. Subjects enrolled in the placebo group for the core treatment period will be randomized in a 1:1 ratio during the extension period to either the Hemay005 Tablets 45 mg BID test group or Hemay005 Tablets 60 mg BID test group for treatment for 40 weeks. For the first week of extended treatment, subjects previously enrolled in the placebo group will need to undergo the same dose titration phase as for the core treatment period (Days 0-6), so that the same dosing schedule as for the two treatment groups would be achieved by the 7th day, in an effort to mitigate the intolerabilities such as gastrointestinal reactions, thus further protecting subjects' safety. If, during the dose titration phase of the extension period or during extended treatment, the subject cannot tolerate the prescribed dose, this will be handled at the investigator's discretion using the same method as for the core treatment period. Drug discontinuation observation period: All subjects in the study (including those who prematurely discontinued treatment for any reason) will be observed for 4 weeks following the end of the last study dose.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Understanding and voluntarily signing the Informed Consent Form (ICF) for this study;
- •Age 18-75 years (inclusive), male or female;
- •Diagnosed as BD based on the ICBD-2013;
- •At least 2 oral ulcers present at V1 (screening), and:
- •at least 2 oral ulcers present at V2 (the day of randomization) when V2 occurs 14-56 days after V1; OR
- •at least 3 oral ulcers present at V2 (the day of randomization) when V2 occurs 0-13 days after V1;
- •Applicability of systemic treatment for oral ulcers: Based on the severity of the disease and the involved area, the investigator determines that the patient's oral ulceration is not suitable for topical treatment or that the patient's oral ulceration cannot be effectively controlled by topical treatment, so that systemic treatment is to be used;
- •Throughout the study period from signing of ICF through 3 months after the last study dose, women of childbearing potential and male subjects who have not undergone vasoligation should use effective contraceptive measures, including vasoligation, abstinence, intrauterine device (IUD), hormones (oral, patches, rings, injections, implants) and barrier methods (diaphragms, cervical caps, sponges, condoms);
- •Being able to comply with the follow-up schedule and other protocol requirements.
Exclusion Criteria
- •Active lesions associated with BD in major organs requiring immunosuppressive treatment, e.g., those in lungs (e.g., pulmonary aneurysm), blood vessels (e.g., thrombophlebitis, recurrent malignant aneurysms), gastrointestinal tract (e.g., gastrointestinal ulcers), and central nervous system (e.g., meningoencephalitis); Note: Patients with refractory BD who experienced gastrointestinal perforation, active bleeding, or obstruction, etc. within 3 months prior to randomization are to be excluded.
- •Any clinically significant heart disease (including but not limited to: unstable ischemic heart disease, NYHA III/IV left ventricular failure, or myocardial infarction) or clinically significant 12-lead ECG abnormalities detected during the 6 months prior to screening, which, at the investigator's discretion, may put the subject at safety risk or may interfere with the study assessments;
- •Use of the following immunomodulatory therapies:
- •Colchicine within 7 days prior to randomization;
- •Perazathioprine, mycophenolate, baritinib, or tofacitinib within 10 days prior to randomization;
- •Cyclosporine, methotrexate, cyclophosphamide, thalidomide, or dapsone within 4 weeks (28 days) prior to randomization;
- •Biologics within 5 half-lives prior to randomization, e.g.:
- •Etanercept within 4 weeks prior to randomization;
- •Infliximab or leflunomide within 8 weeks prior to randomization;
- •Adalimumab, golimumab, abatacept, or tolizumab within 10 weeks prior to randomization;
Arms & Interventions
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 40 weeks.
Intervention: Hemay005
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 40 weeks.
Intervention: Hemay005
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 40 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Efficacy assessed by oral ulcers
Time Frame: week 12
Area under the curve (AUC) of the number of oral ulcers in BD patients from baseline to Week 12
Secondary Outcomes
- efficacy assessed by oral ulcers(week 2, 4, 6, 8, 10, 12)
- pain of oral ulcers assessed by VAS(week 12, 22, 32, 42, 52)
- efficacy assessed by genital ulcers(week 12, 22, 32, 42, 52)
- pain of genital ulcers assessed by VAS(week 12, 22, 32, 42, 52)
- efficacy assessed by BDCAF(week 12, 22, 32, 42, 52)
- efficacy assessed by BSAS(week 12, 22, 32, 42, 52)
- efficacy of skin lesions assessed by PGA score(week 12, 22, 32, 42, 52)
- Quality of life measured by BD QoL(week 12, 22, 32, 42, 52)
- Quality of life measured by SF-36(week 12, 22, 32, 42, 52)
- efficacy assessed by tender and/or swollen joints(week 12, 22, 32, 42, 52)
- efficacy assessed by gastrointestinal activity(week 12, 22, 32, 42, 52)
- efficacy assessed by gastrointestinal symptoms(week 1, 12, 52)
- efficacy assessed by biomarkers.(week 12, 22, 32, 42, 52)
- efficacy assessed by eye symptoms.(week 12, 22, 32, 42, 52)
- population pharmacokinetics (PopPK)(week 4, 12)
- safety assessed by Type, frequency, severity and relationship with drug of AEs(week 1, 2, 4, 6, 8, 10, 12, 22, 32, 43, 52, 56)
- safety and tolerability assessed by discontinuation due to AEs(week 1, 2, 4, 6, 8, 10, 12, 22, 32, 43, 52, 56)
- safety and feasibility assessed by lab examinations(week 1, 2, 4, 6, 8, 10, 12, 22, 32, 43, 52, 56)