A Study to Learn About the Efficacy and Safety of Rimegepant for the Acute Treatment of Migraine in Children and Adolescents.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

31 Aug 2021 → ongoing

Decision date (initial)

2024-07-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2024-512743-23-00

EudraCT number

2020-003517-35

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of rimegepant compared with placebo in the acute treatment of migraine in adolescent
population (12 to less than 18 years of age) as measured by pain freedom at 2 hours post-dose.

Secondary objectives 15

1. To evaluate the efficacy of rimegepant relative to placebo in the acute treatment of migraine in the combined population of children and adolescents (6 to less than 18 years of age) as measured by pain freedom at 2 hours post-dose.
2. To evaluate rimegepant compared to placebo on freedom from the most bothersome symptom (MBS) associated with migraine at 2 hours post-dose in the adolescent population.
3. To evaluate rimegepant compared to placebo on the probabilities of requiring rescue medication within 24 hours and 48 hours of initial treatment in the adolescent population.
4. To evaluate rimegepant compared to placebo on sustained pain freedom from 2 to 24 hours post-dose in the adolescent population.
5. To evaluate rimegepant compared to placebo on sustained pain freedom from 2 to 48 hours post-dose in the adolescent population.
6. To evaluate the effect of rimegepant compared to placebo on the ability to function normally at 2 hours post-dose as reported on the Functional Disability scale in the adolescent population.
7. To evaluate the efficacy of rimegepant relative to placebo in the acute treatment of migraine in children population (6 to less than 12 years of age) as measured by pain freedom at 2 hours post-dose.
8. To evaluate rimegepant relative to placebo on freedom from the most bothersome symptom (MBS) associated with migraine at 2 hours post-dose in children and in the combined population of children and adolescents
9. To evaluate rimegepant relative to placebo on the probabilities of requiring rescue medication within 24 hours and 48 hours of initial treatment in children and in the combined population of children and adolescents.
10. To evaluate rimegepant relative to placebo on sustained pain freedom from 2 to 24 hours post-dose in children and in the combined population of children and adolescents.
11. To evaluate rimegepant relative to placebo on sustained pain freedom from 2 to 48 hours post-dose in children and in the combined population of children and adolescents.
12. To evaluate rimegepant relative to placebo on freedom from photophobia at 2 hours post-dose in adolescents, children, and the combined population of children and adolescents.
13. To evaluate rimegepant relative to placebo on freedom from nausea at 2 hours post-dose in adolescents, children, and the combined population of children and adolescents.
14. To evaluate rimegepant relative to placebo on pain relief at 2 hours post-dose in adolescents, children, and the combined population of children and adolescents.
15. To evaluate rimegepant relative to placebo on time to first report of pain relief in adolescents, children, and the combined population of children and adolescents.

Conditions and MedDRA coding

Acute Migraine (with or without aura)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002812-PIP02-20

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 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.
2. 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.
3. 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 6

1. 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.
2. 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.
3. 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
4. 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).
5. 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 invlolved in the conduct of the study.
6. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 16

1. 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.
2. 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).
3. 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.
4. 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.
5. 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.
6. 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.
7. 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).
8. 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).
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 4

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 131 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications