Clinical trial NCT02291380: A Study to Evaluate Botulinum Toxin Type A for Injection（HengLi®）for Prophylactic Treatment of Chronic Migraine
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Migraine
Keywords: Chronic Migraine
Botulinum Toxin Type A for Injection
Lead sponsor: Lanzhou Institute of Biological Products Co., Ltd
Sponsor class: INDUSTRY
First posted: 2014-11-14
Enrollment: 288
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: Change from baseline in average number of days with headache per month
timeFrame: Baseline (week -4 to 0) and core phase (week 21 to 24)
Secondary outcomes:
measure: the average number of days with headache per month
timeFrame: Baseline and Week 4, 8, 12, 16, 20, 28, 32, 36, 40, 44, 48, 52, 56
measure: the average frequency of headache per month
timeFrame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
measure: the average frequency of migraine per month
timeFrame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
measure: Proportions of subjects
timeFrame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
measure: Change in the average frequency of needing emergency analgesics per month
timeFrame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
measure: Change in the average severity of migraine
timeFrame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
measure: Change in the average duration of migraine
timeFrame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
measure: Migraine Disability Assessment Questionnaire score(MIDAS)
timeFrame: Week 0,12,24,36,48,56
measure: Headache Impact Test (HIT)
timeFrame: Week0,4,8,12,16,20,24,28,32,36,40,44,48,52,56
Other outcomes:
Locations:
Study officials:
affiliation: The General Hospital of People's Liberation Army(301 hospital)
name: Sheng yuan Yu
role: STUDY_DIRECTOR
References: