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

NCT ID: NCT02291380

Last Updated: 2018-01-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 288 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2020-06-30

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.)

Conditions

Chronic Migraine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Botulinum Toxin Type A for Injection

Botulinum Toxin Type A is a specific formulation of a locally injected muscle relaxant whose active ingredient is botulinum toxin type A produced by clostridium botulinum A strain Hall. Excipients contain sucrose, dextran and gelatin.

Group Type: ACTIVE_COMPARATOR

Botulinum Toxin Type A for Injection

Intervention Type: DRUG

In these studies ,patients received a minimum intramuscular (IM) dose of 155 U of Botulinum Toxin Type A（HengLi®）administered to 31 injection sites across 7 head and neck muscles using a fixed-site, fixed-dose injection paradigm (each injection was 5 U in 0.1 mL). In addition, up to 40 U Botulinum Toxin Type A,administered IM to 8 additional injection sites across 3 head and neck muscles, was allowed, using a follow-the-pain approach. Thus, the minimum dose was 155 U and the maximum dose was 195 U. In the core phase, two doses of HengLi® will be injected.In the extension phase, three doses of HengLi® will be injected.

Placebo

The placebo does not include botulinum toxin A ,but includes sucrose, dextran and gelatin.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

In these studies, patients received placebo administered to 31 injection sites across 7 head and neck muscles using a fixed-site, fixed-dose injection paradigm (each injection was 0.1 mL). In addition, up to 0.8 mL placebo, administered IM to 8 additional injection sites across 3 head and neck muscles, was allowed, using a follow-the-pain approach. In the core phase, two doses of placebo will be injected.

Interventions

Botulinum Toxin Type A for Injection

In these studies ,patients received a minimum intramuscular (IM) dose of 155 U of Botulinum Toxin Type A（HengLi®）administered to 31 injection sites across 7 head and neck muscles using a fixed-site, fixed-dose injection paradigm (each injection was 5 U in 0.1 mL). In addition, up to 40 U Botulinum Toxin Type A,administered IM to 8 additional injection sites across 3 head and neck muscles, was allowed, using a follow-the-pain approach. Thus, the minimum dose was 155 U and the maximum dose was 195 U. In the core phase, two doses of HengLi® will be injected.In the extension phase, three doses of HengLi® will be injected.

Intervention Type: DRUG

Placebo

In these studies, patients received placebo administered to 31 injection sites across 7 head and neck muscles using a fixed-site, fixed-dose injection paradigm (each injection was 0.1 mL). In addition, up to 0.8 mL placebo, administered IM to 8 additional injection sites across 3 head and neck muscles, was allowed, using a follow-the-pain approach. In the core phase, two doses of placebo will be injected.

Intervention Type: DRUG

Other Intervention Names

HengLi®

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lanzhou Institute of Biological Products Co., Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sheng yuan Yu

Role: STUDY_DIRECTOR

The General Hospital of People's Liberation Army(301 hospital)

Other Identifiers

HengLi003

Identifier Type: -

Identifier Source: org_study_id