RIMEGEPANT for Acute migraine

Inclusion criteria

• {"criterion_text":"- Signed Written Informed Consent a. The participant must be capable of communicating with the site personnel. b. The participant is able to understand the Informed Assent Form (IAF) and the participant’s parent(s)/legal representative(s) (according to local regulations) are/is able to read and understand the Informed Consent Form (ICF). c. The participant has signed the IAF and the participant’s parent(s)/legal representative(s) (according to local regulations) have/has signed the ICF prior to the conduct of any study-specific procedures. d. The participant and the participant’s parent(s)/legal representative(s) (as required according to local regulations) are/is willing and able to attend study appointments within the specified time windows. e. The participant must be able to read and comprehend written instructions and be willing to complete all questionnaires under supervision of legal representative(s) as required by the protocol.\n- Target Population a. History of migraine (with or without aura) for > 6 months before Screening according to the IHS Classification ICHD-319 specifications for pediatric migraine. History may be verified using both medical records and recall by the participant and/or participant’s parent(s)/legal representative(s). b. History of 1 to 8 moderate or severe attacks per month during the 2 months prior to enrollment. A history of attacks lasting approximately > 3 hours without treatment. History may be verified using both medical records and recall by the participant and/or participant’s parent(s)/legal representative(s). c. Participants on prophylactic migraine medication are permitted to remain on therapy if the dose has been stable for at least 12 weeks prior to the Baseline Visit, and the dose is not expected to change during the course of the study. i. Participants may remain on one (1) medication with possible migraine prophylactic effects, excluding CGRP antagonists [biologic or small molecule], during the Single-Blind and Double-Blind Treatment phases. ii. Concomitant use of a CGRP antagonist, such as erenumab or fremanezumab, is prohibited. iii. Participants who previously discontinued prophylactic migraine medication must have done so at least 90 days prior to the Screening Visit. d. Participants are required to verbally distinguish between migraine and other types of headaches. e. Participants must have a weight >15 kg at the Screening and Baseline Visits. For EU countries only: Participants 12 to < 18 years of age must have a body weight of >25 kg at Screening and Baseline Visits. f. Participants must have adequate venous access for blood sampling.\n- Age and Reproductive Status a.Male and female participants 6 to less than 18 years of age. Participants must not reach their 18th birthday during the study. Study sites must only enroll patients of age and body weight categories for which the Sponsor has granted the site written approval to commence recruitment. b. The participant, if a female who is sexually active and of childbearing potential must be willing to use a highly effective or an acceptable effective contraceptive method during the study. See Appendix 4: Contraceptive and Barrier Guidance c. The participant, if a female age 8 or older (or younger girls who, at the discretion of the investigator, are deemed to be of reproductive potential), must have a confirmed negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) at the Screening Visit and Baseline. d. Females must not be breastfeeding. e. No clinically significant abnormality identified on the medical or laboratory evaluation. A participant with a clinical abnormality or laboratory parameters outside the lab normal reference range may be included only if the investigator considers that the finding is not clinically significant and will not introduce additional risk factors and will not interfere with the study procedures."}

Exclusion criteria

• {"criterion_text":"- Target Disease Exclusion a. Participant has a history of cluster headache or hemiplegic migraine headache. b. The participant has a continuous migraine (defined as an unrelenting headache) during within 1 month prior to Screening Visit.c. The participant has a history or diagnosis of persistent aura without infarction, migrainous infarction, migraine aura-triggered seizure, chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or unusual migraine subtypes such as hemiplegic migraine (sporadic and familial), ophthalmoplegic migraine, or migraine with neurological accompaniments that are not typical of migraine aura (diplopia, altered consciousness, or long duration). d. The participant has a confounding and clinically significant pain syndrome that may interfere with the participant’s ability to participate in this study.\n- Medical History and Concurrent Diseases a. The participant has any current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6 months prior to the Screening Visit. Participants with a lifetime history of psychosis and/or mania are excluded. b. History of suicidal behavior or the participant is at risk of self-harm or harm to others. c. History of major psychiatric disorder. Participants with anxiety disorder and/or mild major depressive disorder are permitted in the study if they are considered by the investigator to be stable and are taking no more than 1 medication for each disorder. Participants must have been on a stable dose within the 3 months before the Baseline Visit. d. The participant has a current diagnosis or history of substance abuse (excluding nicotine and caffeine) or alcohol abuse (DSM-5® criteria) < 2 years prior to the Screening Visit, as verified with legal representative(s) and in the opinion of the Investigator. e. The participant has reported current use of, or has tested positive at the Screening visit for, drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, MDMA, methamphetamines, oxycodone, phencyclidine). Marijuana and all forms of ingested or inhaled cannabidiol and tetrahydrocannabinol containing products are prohibited. i. Participants who are positive at screening for drugs of abuse, and who are on a prescribed medication for an approved indication (eg, ADHD), will be allowed into the study at the Investigator’s discretion. This determination by the Investigator must be well documented in the source medical records. The stimulant dose must be stable from 3 months prior to baseline until the end of treatment visit occurs. f. The participant has a history of cancer. g. The participant has any other disorder for which the treatment takes priority over treatment of migraine or is likely to interfere with study treatment or safety assessments.h. The participant has a history of moderate or severe head trauma or other neurological disorder (including seizure disorder) or systemic medical disease that is, in the investigator’s opinion, likely to affect central nervous system functioning. i. The participant has had recent or planned surgery, requiring general anesthesia, <8 weeks prior to the Screening Visit. j. The participant has or has had one or more of the following conditions that is/are considered clinically relevant in the context of the study: i. Uncontrolled hypertension ii. Cardiovascular disease iii. Cardiomyopathy iv. Serious heart rhythm abnormalities v. Cerebrovascular disease (for example CNS Vascular ischemia) vi. Thromboembolic event vii. Diabetes viii. Raynaud’s disease ix. Life-threatening allergy (for example anaphylaxis) k. The participant has had gastrointestinal surgery that interferes with physiological absorption and motility (i.e., gastric bypass, duodenectomy, or gastric banding). l. The participant has one or more clinically significant out-of-range vital signs at the Screening or Baseline Visit. m. The participant has a current diagnosis of active viral hepatitis or a medical history of chronic liver disease. n. The participant has known infection with HIV, unless participant has CD4+ count >200 and undetectable viral load.\n- Allergies and Adverse Drug Reactions a. The participant has a history of severe drug allergy or hypersensitivity or known hypersensitivity or intolerance to the excipients in rimegepant. b. History of drug or other allergy which, in the opinion of the investigator, makes the participant unsuitable for participation in the study\n- ECG and Laboratory Test Findings a. Clinically significant abnormality identified on the medical or laboratory evaluation. A participant with a clinical abnormality or laboratory parameters outside the reference range may be included only if the investigator considers the finding not clinically significant, that it will not introduce additional risk factors, nor interfere with the study procedures. The following laboratory values are exclusionary: i. Serum creatinine value >1.5 x ULN ii. Serum Total bilirubin > ULN, unless participant has known or suspected Gilbert’s Syndrome iii. AST or ALT >2 x ULN (AST and/or ALT may be repeated once during the Screening Phase for assessment of eligibility) b. The participant has evidence of organ dysfunction or any clinically significant deviation from normal on physical examination, vital signs, 12-lead electrocardiogram (ECG), or clinical laboratory determinations beyond what is consistent with the target population. c. The participant has, at the Screening Visit: an abnormal ECG that is clinically significant based on the investigator’s evaluation of the central reader’s interpretation (Any evaluation of QT interval should be based on the Fridericia correction where QTcF = QT/RR0.33).\n- Other Exclusion Criteria a. The participant has a sibling, or member of the same household, that has or will be participating in the BHV3000-311 study. b. Any yes response on the Columbia-Suicide Severity Rating Scale (C-SSRS) for the period of 30 days prior to Screening. c. The participant has been enrolled in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.d. The participant has been exposed to any calcitonin gene-related peptide (CGRP) receptor antagonist treatment or CGRP antibody (including exposure in a study investigating a CGRP antagonist or antibody) <6 months prior to the Screening Visit. e. Prisoners or participants who are incarcerated, i.e. Children’s residential facilities. f. Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness. g. Participation in any other investigational clinical trial while participating in this clinical trial. Participants in a COVID-19 mRNA vaccine study (vaccine must be authorized under emergency use authorization or approval within the respective country) at least 30 days post last dose of the vaccine are permitted to be screened for this study. h. The participant has a clinically significant history of depression or suicidal thoughts within the previous 6 months prior to Screening, as verified with legal representative(s) and in the opinion of the Investigator. i. The participant has a physical finding in the mouth or tongue that would be likely to interfere with successful completion of the dosing procedure (orthodontic braces are permitted). j. The participant has a history of intolerance to venipuncture. k. The participant is, in the investigator’s opinion, unlikely to comply with the protocol or is unsuitable for any reason (including any known, suspected, or confirmed infections in the participant or participant’s parent(s)/legal representative(s) that may put the participant or study staff at risk [according the study site guidelines]).l. Participation in the BHV3000-121 study.m. Children or grandchildren who are direct descendants of investigator site staff or sponsor and sponsor delegate employees directly invloved in the conduct of the study.\n- Prohibited Medications a. The participant has a disease or takes medication that could, in the investigator’s opinion, interfere with the assessments of safety or tolerability, or interfere with the conduct or interpretation of the studyb. Please see Section 5.4 for prohibited medications and Section 5.5 for allowable prophylactic and standard of care medications"}

Primary endpoints

• {"endpoint_text":"- Pain freedom will be assessed using the number and percentage of participants that report no pain at 2 hours post double-blind treatment dose measured on a 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe) in adolescent population (12 to less than 18 years of age).","definition_or_measurement_approach":"Assessed as number and percentage of participants reporting no pain (score 0) at 2 hours post-dose on a 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe) in adolescents (12 to <18 years)."}

Secondary endpoints

• {"endpoint_text":"- Pain freedom will be assessed using the number and percentage of participants that report no pain at 2 hours post double-blind treatment dose in the combined population of children and adolescents 6 to less than 18 years of age). Participants with no pain are those who report 0 on the 4-point numeric scale in adolescents and who report Face 1 on the 5-Face visual analogue scales (VAS), in children.","definition_or_measurement_approach":"Number and percentage reporting no pain at 2 hours post-dose: adolescents = score 0 on 4-point numeric scale; children = Face 1 on 5-face VAS."}
• {"endpoint_text":"- Freedom from the MBS associated with migraine will be assessed using the number and percentage of participants that report the absence of their MBS at 2 hours post double-blind treatment dose in the adolescent population. The MBS nausea, phonophobia or photophobia) will be measured using a binary scale (0=absent, 1=present).","definition_or_measurement_approach":"Absence of most bothersome symptom (nausea, phonophobia, or photophobia) at 2 hours post-dose measured binary (0=absent, 1=present) in adolescents."}
• {"endpoint_text":"- The probabilities of requiring rescue medication will be assessed using the number and percentage of participants that take rescue medication within 24 hours and within 48 hours after administration of double-blind treatment (rimegepant or placebo) in the adolescent population.","definition_or_measurement_approach":"Number and percentage of participants taking rescue medication within 24 and 48 hours after double-blind treatment in adolescents."}
• {"endpoint_text":"- Sustained pain freedom, from 2 to 24 hours post double-blind treatment dose, will be assessed using the number and percentage of participants that do not use any rescue medications, and do not experience any headache pain through the time period of interest, in the adolescent population.","definition_or_measurement_approach":"Participants who report no headache pain and do not use rescue medication from 2 to 24 hours post-dose; assessed as number and percentage in adolescents."}
• {"endpoint_text":"- Sustained pain freedom, from 2 to 48 hours post double-blind treatment dose, will be assessed using the number and percentage of participants that do not use any rescue medications, and do not experience any headache pain through the time period of interest, in the adolescent population.","definition_or_measurement_approach":"Participants who report no headache pain and do not use rescue medication from 2 to 48 hours post-dose; assessed as number and percentage in adolescents."}
• {"endpoint_text":"- The proportion of participants able to function normally, at 2 hours post double-blind treatment dose, will be assessed using the number and percentage of participants that self-report as “normal” on the Functional Disability scale, in the adolescent population.","definition_or_measurement_approach":"Number and percentage of participants self-reporting 'normal' on the Functional Disability scale at 2 hours post-dose in adolescents."}
• {"endpoint_text":"- Pain freedom will be assessed using the number and percentage of participants that report no pain (Face 1) at 2 hours post double-blind treatment dose, measured by a 5-Face VAS (Face 5 = ‘severe pain’, Faces 4 and 3 = ‘moderate pain’, Face 2 = ‘mild pain’, Face 1 = ‘no pain’) in the children population (6 to less than 12 years of age).","definition_or_measurement_approach":"Number and percentage reporting Face 1 (no pain) on 5-face VAS at 2 hours post-dose in children (6 to <12 years)."}
• {"endpoint_text":"- Freedom from the most bothersome symptom (MBS) associated with migraine will be assessed using the number and percentage of participants that report the absence of their MBS at 2 hours post double-blind treatment dose in children and in the combined population of children and adolescents. The MBS (nausea, phonophobia or photophobia) will be measured using a binary scale (0=absent, 1=present).","definition_or_measurement_approach":"Binary assessment (0=absent, 1=present) of MBS absence at 2 hours post-dose in children and combined children+adolescents; reported as number and percentage."}
• {"endpoint_text":"- The probabilities of requiring rescue medication will be assessed using the numbers and percentage of participants that take rescue medication within 24 hours and within 48 hours after administration of double-blind study intervention (rimegepant or placebo) in children and in the combined population of children and adolescents.","definition_or_measurement_approach":"Number and percentage taking rescue medication within 24 and 48 hours post-dose in children and combined population."}
• {"endpoint_text":"- Sustained pain freedom, from 2 to 24 hours post double-blind treatment dose, will be assessed using the number and percentage of participants that do not use any rescue medications, and do not experience any headache pain through the time period of interest in children and in the combined population of children and adolescents.","definition_or_measurement_approach":"No headache pain and no rescue medication use from 2 to 24 hours post-dose; number and percentage in children and combined population."}
• {"endpoint_text":"- Sustained pain freedom, from 2 to 48 hours post double-blind treatment dose, will be assessed using the number and percentage of participants that do not use any rescue medications, and do not experience any headache pain through the time period of interest, in children and in the combined population of children and adolescents.","definition_or_measurement_approach":"No headache pain and no rescue medication use from 2 to 48 hours post-dose; number and percentage in children and combined population."}
• {"endpoint_text":"- Freedom from photophobia will be assessed by tabulating the number and percentage of participants that report the absence of photophobia at 2 hours post double-blind treatment dose in the subset of participants that reported the presence of photophobia at headache baseline, in adolescents, children, and the combined population of children and adolescents.","definition_or_measurement_approach":"Number and percentage of participants (subset with baseline photophobia) reporting absence of photophobia at 2 hours post-dose in adolescents, children, and combined population."}
• {"endpoint_text":"- Freedom from phonophobia will be assessed by tabulating the number and percentage of participants that report the absence of phonophobia at 2 hours post double-blind treatment dose in the subset of participants that reported the presence of phonophobia at headache baseline, in adolescents, children, and the combined population of children and adolescents.","definition_or_measurement_approach":"Number and percentage (subset with baseline phonophobia) reporting absence of phonophobia at 2 hours post-dose."}
• {"endpoint_text":"- Freedom from nausea will be assessed by tabulating the number and percentage of participants that report the absence of nausea at 2 hours post double-blind treatment dose in the subset of participants that reported the presence of nausea at headache baseline, in adolescents, children, and the combined population of children and adolescents.","definition_or_measurement_approach":"Number and percentage (subset with baseline nausea) reporting absence of nausea at 2 hours post-dose."}
• {"endpoint_text":"- Pain relief at 2 hours post double-blind treatment dose, will be assessed using the number and percentage of participants that report a pain level of moderate or severe at baseline and then report a pain level of none or mild at 2 hours post double-blind treatment dose in adolescents, children, and the combined population of children and adolescents.","definition_or_measurement_approach":"Participants with baseline moderate/severe pain reporting none/mild at 2 hours post-dose; number and percentage in adolescents, children, and combined population."}
• {"endpoint_text":"- Time to first report of pain relief will be based on the first time point a participant reports a pain level of none or mild post double-blind treatment dose in adolescents, children, and the combined population of children and adolescents.","definition_or_measurement_approach":"Time-to-event defined as first timepoint participant reports none or mild pain post-dose; assessed in adolescents, children, and combined population."}

Methods

• AutoCruitment digital campaign / digital adverts (country-specific digital campaigns documented for ES/PL/SE) including digital ad image libraries and cookie/privacy policy.
• Phone screener (AutoCruitment Phone Screener) for initial eligibility contact.
• Animated 2D videos and multimedia materials for assent and participant information (assent process videos, 'What to expect', 'Migraine attacks', product information) targeted to children/adolescents and parents/legal representatives.
• School nurse referral letters (country-specific) to reach school-aged children/adolescents.
• Study posters, brochures, and patient invite letters for site-based outreach.
• Site-based outreach and 'Migraine Outreach Media Board - Site Use' materials for clinic referrals.
• eCOA reminders and electronic diaries (post-dose diaries) to support data collection and retention.

Spain

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

582

Number Of Sites

3

Number Of Participants

70

Poland

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

26-01-2026

Processing Time Days

585

Number Of Sites

4

Number Of Participants

67

Sweden

Earliest CTIS Part Ii Submission Date

20-06-2024

Latest Decision Or Authorization Date

03-02-2026

Processing Time Days

593

Number Of Sites

2

Number Of Participants

18

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Syneos Health Netherlands B.V.

Responsibilities

Vendor Management (operational vendor management and related support)

Name

Q Squared Solutions Limited

Responsibilities

Central Laboratory services

Name

Eresearchtechnology Inc.

Responsibilities

Cardiac Safety Assessment: central ECG services; eDiary solutions provider

Name

Endpoint Clinical Inc.

Responsibilities

IVRS - treatment randomization

Third parties

• {"country":"Netherlands","full_name":"Syneos Health Netherlands B.V.","duties_or_roles":"Vendor Management (and other vendor/operational support roles listed)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Central Laboratory services","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Cardiac Safety Assessment: central ECG services; eDiary solutions provider","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"IVRS - treatment randomization","organisation_type":"Pharmaceutical company"}