a study to evaluate botulinum toxin type a for injection（hengli®）for prophylactic treatment of chronic migraine

Conditions: Chronic Migraine

Summary: 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.)

Eligibility criteria:
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.

Keywords: chronic migraine botulinum toxin type a for injection