A Study to Evaluate Botulinum Toxin Type A for Injection（HengLi®）for Prophylactic Treatment of Chronic Migraine

A Multi-center, Randomized, Double-blind, Placebo Parallel-Controlled Clinical Study to Evaluate the Safety and Efficacy of Botulinum Toxin Type A for Injection (HengLi ®) for Prophylactic Treatment of Chronic Migraine in Adults

A study, multi-center, randomized, double-blind, placebo parallel-controlled method, will be carried out to evaluate the safety and efficacy of Botulinum Toxin Type A for injection (HengLi®) for prophylactic treatment with chronic migraine in adults. In the core phase, two treatments of HengLi® or the placebo will be administrated (randomized at a ratio of 2:1, the target number is 288 subjects). In the extension phase, three treatments of HengLi® will be still administrated on 288 subjects recruited ever.

Subjects in the core phase will be randomized into two groups: Botulinum Toxin Type A (HengLi®) (155U to 195U) or placebo. Study include a 28-day baseline screening period, a 24-week core phase with 2 administrations, and a 32-week extension phase with 3 administrations .Subjects enrolled will get a e-headache-diary in recording their headache symptoms and acute headache medications.

HengLi® was administered as 31 fixed-site, fixed-dose (5U), i.m. injections across 7 specific head/neck muscle areas every 12 weeks (weeks 0, 12, 24, 36, and 48). At the investigator's discretion, up to 40 U of additional HengLi® could have been administered among 3 muscle groups (occipitalis, temporalis, or trapezius) using a protocol-defined paradigm. Hence the maximum dose per treatment cycle was 195 U over 39 sites.

Efficacy Outcome Measures should be evaluated by headache diary, HIT-6 score and MIDAS score . The primary Outcome Measure: Change from baseline in the average number of days with headache per month (The last 4 weeks during the core phase and the 4 weeks during the baseline period should be compared with the number of headache days per month on average.)

Inclusion Criteria:

• Age≥18 and ≤65, male or female;
• Subjects voluntarily sign the informed consent.
• Patients complying with the ICHD-3(β) diagnostic criteria for chronic migraine.

Exclusion Criteria:

• Females who are pregnant, nursing, or planning a pregnancy during the study period, or females of childbearing potential, not using a reliable means of contraception;
• Known allergy or sensitivity to study medication or its component;
• Subjects having accepted prophylactic treatments of migraine (e.g. propranolol, metoprolol, bisoprolol, flunarizine, valproate, topiramate, gabapentin, naproxen, aspirin, amitriptyline, candesartan, lisinopril, etc.) within the 4 weeks before screening;
• Subjects with cardiac functional insufficiency;
• Subjects with renal insufficiency (serum creatinine>1.5 times ULN);
• Subjects with hepatic diseases (ALT or AST>twice ULN);
• Subjects with systemic myoneural junction diseases (e.g. myasthenia, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, etc.);
• Subjects with a history of facial palsy;
• Infection or dermatological condition at the injection sites;
• Patients with other types of migraine that do not comply with the diagnostic criteria for chronic migraine;
• Subjects ever took any type of botulinum toxin therapy in the past 6 months;
• Subjects who have used aminoglycoside antibiotics in the recent week or need to use aminoglycoside antibiotics during conduct of the clinical study;
• Subjects live with severe cognitive disorder or mental illness, outcomes will not be measured objectively;
• Subjects live with alcohol or drug abuse;
• Subjects who have been involved in other clinical studies over the 3 months prior to this study;
• Investigator's opinion that the subject has a concurrent condition(s) that may put the subject at significant risk, may confound the study results, or may interfere significantly with the conduct of the study.