Chronic MigrainePhase 3NCT02291380
A Study to Evaluate Botulinum Toxin Type A for Injection（HengLi®）for Prophylactic Treatment of Chronic Migraine
A Phase 3 study testing Botulinum Toxin Type A for Injection in people with Chronic Migraine, run by Lanzhou Institute of Biological Products Co., Ltd.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Migraine
- What is being tested?
- Botulinum Toxin Type A for Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 288 participants
- Where
- No sites listed yet
- Study dates
- Sep 2014to Jun 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
Show all 16Show fewer
- 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.
About this study
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
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.
Read the 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
- Being tested
- Botulinum Toxin Type A for Injection, Placebo
- Keywords
- Chronic Migraine, Botulinum Toxin Type A for Injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum Toxin Type A for InjectionDrug
Also called HengLi®
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Botulinum Toxin Type A for Injection | Active comparator | 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. Receives: Drug: Botulinum Toxin Type A for Injection |
| Placebo | Placebo comparator | The placebo does not include botulinum toxin A ,but includes sucrose, dextran and gelatin. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in 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.
Measured: Baseline (week -4 to 0) and core phase (week 21 to 24)
Secondary outcomes (9)
the average number of days with headache per month
Change in the average number of days with headache per month versus the baseline
Measured: Baseline and Week 4, 8, 12, 16, 20, 28, 32, 36, 40, 44, 48, 52, 56
the average frequency of headache per month
Change in the average frequency of headache per month versus the baseline
Measured: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
the average frequency of migraine per month
Change in the average frequency of migraine per month versus the baseline
Measured: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
Proportions of subjects
Proportions of subjects with a reduction in the average frequency of migraine per month≥50% and ≥30%
Measured: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
Change in the average frequency of needing emergency analgesics per month
The number of days with the need of emergency analgesics during the observation period divided by the number of days in the observation period and multiplied by 28. The need of emergency analgesics refers to use of analgesics in case of attacks or use of drugs in advance to prevent pain attacks.
Measured: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
Change in the average severity of migraine
Sum of severity scores of migraine episodes during the observation period divided by the number of migraine episodes. The severity of each migraine episode is the severity when the pain is the fiercest, expressed using VAS (0-10).
Measured: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
Change in the average duration of migraine
Sum of durations of migraine episodes during the observation period divided by the number of migraine episodes.
Measured: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
Migraine Disability Assessment Questionnaire score(MIDAS)
Change in the MIDAS per month versus the baseline
Measured: Week 0,12,24,36,48,56
Headache Impact Test (HIT)
Change in the HIT per month versus the baseline
Measured: Week0,4,8,12,16,20,24,28,32,36,40,44,48,52,56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2014 (estimated)
- Study startSep 2014
- Primary completionDec 2019 (estimated)
- Study completionJun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 288 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lanzhou Institute of Biological Products Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sheng yuan Yu, Study director, The General Hospital of People's Liberation Army(301 hospital)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02291380
- Sponsor's protocol ID
- HengLi003
- Status last verified
- Jan 2018
- First submitted
- 11 Nov 2014
- Last updated
- 3 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02291380
- Acronym / sponsor ID
- HengLi003
- Conditions
- Chronic Migraine
- Keywords
- Chronic Migraine, Botulinum Toxin Type A for Injection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 288 participants (estimated)
- Lead sponsor
- Lanzhou Institute of Biological Products Co., LtdIndustry (pharma, biotech, devices)
- Study start
- Sep 2014
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 14 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Botulinum Toxin Type A for Injection | Active comparator | Drug: Botulinum Toxin Type A for InjectionBotulinum 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. |
| Placebo | Placebo comparator | Drug: PlaceboThe placebo does not include botulinum toxin A ,but includes sucrose, dextran and gelatin. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (16 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Botulinum Toxin Type A for InjectionAlso: HengLi®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. | Drug | Botulinum Toxin Type A for Injection |
| PlaceboIn 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. | Drug | Placebo |
Primary outcome
Change from baseline in average number of days with headache per month
Time frame: Baseline (week -4 to 0) and core phase (week 21 to 24)
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.
9 secondary outcomes
the average number of days with headache per month
Time frame: Baseline and Week 4, 8, 12, 16, 20, 28, 32, 36, 40, 44, 48, 52, 56
the average frequency of headache per month
Time frame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
the average frequency of migraine per month
Time frame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
Proportions of subjects
Time frame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
Change in the average frequency of needing emergency analgesics per month
Time frame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
Change in the average severity of migraine
Time frame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
Change in the average duration of migraine
Time frame: Baseline and Week 4,8,12,16,20,24,28,32,36,40,44,48,52,56
Migraine Disability Assessment Questionnaire score(MIDAS)
Time frame: Week 0,12,24,36,48,56
Headache Impact Test (HIT)
Time frame: Week0,4,8,12,16,20,24,28,32,36,40,44,48,52,56
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2018.
- Individual participant dataSharing planned: No
Related trials for Chronic Migraine
Not yet recruiting
Laser Acupuncture for Chronic Migraine: Clinical Response, Traditional Chinese Medicine Syndrome Patterns, and Brain Function
Chronic Migraine Headache
Active, not recruitingPhase 3
A Study to Learn About the Study Medicine Called Rimegepant in Adolescents With Frequent Migraine
Migraine
RecruitingEarly Phase 1
Virtual Reality and Biofeedback for Adolescents With Chronic Dizziness
Persistent Postural Perceptual Dizziness, Vestibular Migraine
RecruitingObservational study
Overlapping Pain Trajectory Study
Migraine, Musculoskeletal Pain
Not yet recruiting
EMBRACE Study: Enduring Migraine Benefit From Responsive Artery Coil Embolization
Migraine Disorders, Refractory Migraine
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sheng yuan Yu study director
The General Hospital of People's Liberation Army(301 hospital)
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Botulinum Toxin Type A for Injection in people with Chronic Migraine, run by Lanzhou Institute of Biological Products Co., Ltd.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in average number of days with headache per month (time frame: Baseline (week -4 to 0) and core phase (week 21 to 24)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2018; AzTrials last refreshed its copy on 27 Oct 2026.