A Multicentre, Randomised, Double-blind, Placebo-controlled, Dose Escalation and Dose Finding Phase II Study to Evaluate the Safety and Efficacy of IPN10200 in the Prevention of Episodic or Chronic Migraine in Adults
概览
- 阶段
- 2 期
- 干预措施
- IPN10200
- 疾病 / 适应症
- Episodic Migraine
- 发起方
- Ipsen
- 入组人数
- 641
- 试验地点
- 235
- 主要终点
- Percentage of participants experiencing any Adverse Event (AEs) including treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse event of special interest (AESI) and AE leading to treatment discontinuation
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
A migraine is a headache with severe throbbing pain or a pulsating sensation, usually on one side of the head. It is often accompanied by feeling or being sick and a sensitivity to bright lights and sound. Migraines are caused by a series of events when the brain gets stimulated or activated, which causes the release of chemicals that cause pain. IPN10200 is a medication that stops the release of these chemical messengers.
Participants with episodic migraine (EM) or chronic migraine (CM) will be included in both Step 1 and Step 2. "Headache days" are when participants experience headaches that meet the criteria for a migraine or a headache without the additional migraine-specific symptoms. "Migraine days" occur when the headache displays clear migraine characteristics.
This study aims to determine:
- The safety and efficacy of injecting IPN10200 directly into the muscles of the head and neck to prevent EM and CM,
- The right amount (dose) of IPN10200 to inject at each point,
- The total amount (dose) of IPN10200 that provides the best balance between safety and efficacy preventing migraines.
Participants will need to complete a daily electronic migraine Diary (eDiary) and questionnaires throughout the study. The total study duration for a participant will be up to 44 weeks.
详细描述
The study will consist of 3 periods: 1. A 'screening period' to assess whether the participant can take part in the study. 2. Step 1 is divided in two cohorts. The study will assess sequentially the safety of two doses of IPN10200, a lower dose in the cohort 1 and a higher dose in cohort 2. Participants will be administered with the study drug or placebo. The treatment is injected in muscles of the head, face and neck. The safety of participants is monitored throughout the 36 weeks at each cohort. 3. Step 2: In this step, new eligible participants will be divided into two groups based on their diagnosis (EM or CM). These groups will then be randomly assigned to one of three intervention groups: Dose A, Dose B, or a placebo. The intervention will be given in a series of injections in muscles of the head, face and neck. Participants will be monitored for both efficacy and safety until they complete the Week 36 visit (the end of study).
研究者
入排标准
入选标准
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF. Participant has provided written informed consent and signed privacy/data protection documentation;
- •Male or female ≥18 to 80 years of age at the time of signing the informed consent;
- •Diagnosis of either EM or CM, per ICHD-3 criteria, for at least 12 months prior to the screening visit;
- •Diagnosis of migraine at ≤50 years of age;
- •Participants in the EM group: History of EM diagnosis and headache frequency (i.e. migraine and non-migraine headache): ≤14 headache days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary; migraine frequency: ≥6 migraine days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary;
- •Participants in the CM group: History of CM diagnosis and headache frequency (i.e. migraine and non-migraine headache): ≥15 headache days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary; migraine frequency: ≥8 migraine days in the 4 weeks prior to randomisation on study Day 1 based on information recorded in the eDiary;
- •Participant with a history of use of at least one preventive treatment for migraine.
排除标准
- •History or current diagnosis of migraine with brainstem aura, retinal migraine, complications of migraine, tension-type headache, trigeminal autonomic cephalalgias, hypnic headache, hemicrania continua or new daily persistent headache;
- •Headache attributed to another disorder (e.g. secondary headaches), except medication overuse headache (MOH);
- •Current uncontrolled psychiatric or psychological condition, or one that could confound assessment of headaches/migraines or interfere with study participation;
- •Risk of self-harm or harm to others as evidenced by past suicidal behaviour or endorsing items 3, 4, or 5 on the C-SSRS at screening or Day
- •Participants presenting with a swallowing disorder of any origin which might be exacerbated by botulinum toxin treatment, such as:
- •\- Grade 3 or 4 on the Dysphagia Severity Scale (severe dysphagia) with swallowing difficulties and requiring a change in diet.
- •Clinically relevant skin condition or infection that could interfere with injection of study intervention;
- •Participant has any medical condition or situation that would make them unsuitable for participation in the study;
- •Participant receiving more than one allowable concomitant migraine preventive treatment;
- •Known history of an inadequate response to \>4 medications prescribed for the prevention of migraine (2 of which have different mechanisms of action to botulinum toxin);
研究组 & 干预措施
Step 1 - Cohort 1- IPN10200
Participants will receive IPN10200 dose A through injections at Day 1.
干预措施: IPN10200
Step 1 - Cohort 1 - Placebo
Participants will receive placebo through injections at Day 1.
干预措施: Placebo
Step 1 - Cohort 2 - IPN10200
Participants will receive IPN10200 dose B through injections at Day 1.
干预措施: IPN10200
Step 1 - Cohort 2 - Placebo
Participants will receive placebo through injections at Day 1.
干预措施: Placebo
Step 2- EM group IPN10200 Dose A
Dose A will be administered to the participants in a single treatment cycle.
干预措施: IPN10200 dose A
Step 2- EM group IPN10200 Dose B
Dose B will be administered to the participants in a single treatment cycle
干预措施: IPN10200 dose B
Step 2- EM group placebo
Placebo will be administered to the participants in a single treatment cycle
干预措施: Placebo
Step 2- CM group IPN10200 Dose A
Dose A will be administered to the participants in a single treatment cycle
干预措施: IPN10200 dose A
Step 2- CM group IPN10200 Dose B
Dose B will be administered to the participants in a single treatment cycle
干预措施: IPN10200 dose B
Step 2- CM group placebo
Placebo will be administered to the participants in a single treatment cycle
干预措施: Placebo
结局指标
主要结局
Percentage of participants experiencing any Adverse Event (AEs) including treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse event of special interest (AESI) and AE leading to treatment discontinuation
时间窗: For step 1: From baseline until end of study at Week 36
An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE is an AE for which the start date is on or after the date that the intervention began.
Percentage of participants with clinically significant change from baseline in 12-lead Electrocardiogram (ECG) readings
时间窗: For step 1: At all timepoints post injection until Week 36
Percentage of Participants with clinically significant changes from baseline in Laboratory Parameters
时间窗: For step 1: At all timepoints post injection until Week 36
Clinically significant change in laboratory parameters will be reported. The clinical significance will graded by the investigator.
Percentage of Participants With Clinically Significant Changes from baseline in Vital Signs
时间窗: For step 1: At all timepoints post injection until Week 36
Clinically significant changes in vital signs will be reported. The clinical significance will be graded by the investigator.
Percentage of participants with clinically significant change from baseline in facial examination
时间窗: For step 1: At all timepoints post injection until Week 36
Clinically significant changes in facial examination and focused neurological/physical examinations will be reported. The clinical significance will be graded by the investigator.
Treatment-emergence of suicidal ideation/suicidal behaviour
时间窗: For step 1: At all timepoints post injection until Week 36
It will be assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire that consists of 2 subscales: 1. Ideation severity subscale: questions answered yes/no, severity of ideation scored 1-5 with 5 being most severe 2. Intensity of ideation subscale : scores range from 2-25 with higher scores indicating more severe intensity of ideation.
Percentage of participants with Binding antibodies to IPN10200
时间窗: For step 1: At baseline, Week 4, Week 12 and Week 36.
Percentage of participants with neutralising antibodies to IPN10200
时间窗: For step 1: At baseline, Week 4, Week 12 and Week 36.
Change from baseline in the number of Monthly migraine days (MMD)s
时间窗: For step 2: At Week 12 (Weeks 9-12).
次要结局
- Change from baseline in the number of MMD(For Step 1 and step 2: From Week 1 to Week 36.)
- Change from baseline in the number of Monthly Headache Days (MHD)(For Step 1 and step 2: From Week 1 to Week 36)
- Change from baseline in the number of moderate/severe MHD(For Step 1 and step 2: From Week 1 to Week 36)
- Migraine prevention response(For Step 1 and step 2: From Week 1 to Week 36)
- Headache prevention response(For Step 1 and step 2: From Week 1 to Week 36.)
- Change from baseline in the number of days per 4 week period of acute medication use for migraine relief.(For Step 1 and step 2: From Week 1 to Week 36.)
- The use of acute migraine medication (yes or no)(For Step 1 and step 2: From Week 1 to Week 36.)
- Percentage of participants with Binding antibodies to IPN10200(For step 2 : At baseline, Week 4, Week 12 , Week 24 and Week 36.)
- Percentage of participants with neutralising antibodies to IPN10200(For step 2 : At baseline, Week 4, Week 12 , Week 24 and Week 36.)