A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rimegepant in Migraine Prevention in Children and Adolescents ≥ 6 to <18 years of age

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

4 Oct 2022 → ongoing

Decision date (initial)

2024-07-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2024-512382-13-00

EudraCT number

2021-005246-15

ClinicalTrials.gov

NCT05156398

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Prophylaxis

To compare the efficacy of rimegepant to placebo as a preventive treatment for migraine in adolescents (12 to <18 years of age) with episodic migraine., as measured by the mean reduction from the observation period (OP) in the number of migraine days per month over the entire course of the doubleblind treatment (DBT) phase. (A month is defined as 4 weeks for the purpose of this protocol.)

Secondary objectives 4

1. To compare the efficacy of rimegepant to placebo on the proportion of participants that have at least a 50% reduction from the OP in the number of moderate to severe migraine days per month over the entire course of the DBT phase in adolescents with episodic migraine.
2. To compare the efficacy of rimegepant to placebo on the mean reduction from the OP in the number of moderate to severe headache days per month over the entire course of the DBT phase in adolescents with episodic migraine.
3. To compare the efficacy of rimegepant to placebo on the mean reduction from the OP in the number of migraine days per month in the first 4 weeks of the DBT phase in adolescents with episodic migraine.
4. To compare the change from baseline in the Pediatric Quality of Life (PedsQL™) 4.0 Generic Core Scales total score at Week 12 of the DBT phase between rimegepant and placebo in adolescents with episodic migraine.

Conditions and MedDRA coding

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 5

1. Participant has at least a 6-month history of migraine (with or without aura) consistent with a Diagnosis according to the International Classification of Headache Disorders, 3rd Edition, and including the following: - 14 or less headache days per month during the 3-month period prior to the Screening Visit. - 6 or more migraine days during the Observation Period. - 14 or less headache days during the Observation Period. - Pediatric Migraine Disability Assessment Scale (PedMIDAS) Disability Score of >10 to ≤50 at the Baseline (Randomization) Visit. - Participants on prophylactic migraine medication are permitted to remain on therapy if the dose has been stable for at least 3 months (12 weeks) prior to the Screening Phase, and the dose is not expected to change during the course of the study.
2. Participants must have a weight of >15 kg. For EU countries only: Participants of 12 to <18 years of age must have a body weight >25 kg.
3. Male and female participants 6 to <18 years; participants must be less than 18 at the time of signing assent / consent. Participants must not reach their 18th birthday on or before the Randomization (Baseline) visit. The participant, if a female who is sexually active and of childbearing potential must be willing to use one effective method of contraception to avoid pregnancy throughout the study.
4. No 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.
5. Signed written Informed Consent/Assent (where applicable, according to local regulations) prior to the conduct of any study-specific procedures.

Exclusion criteria 13

1. Participants with a history of basilar migraine, cluster headaches, or hemiplegic migraine, continuous migraine within 1 month prior to Screening Visit, history or diagnosis of complications of migraine, 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).
2. The participant has a confounding and clinically significant pain syndrome that may interfere with the participant’s ability to participate in this study. History of major psychiatric disorder or 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. History of suicidal behavior or the participant is at risk of self-harm or harm to others.
3. The participant has a current diagnosis or history of substance abuse (excluding nicotine and caffeine) or alcohol abuse (DSM-5®19 criteria) < 2 years prior to the Screening Visit, as verified with legal representative(s) and in the opinion of the Investigator.
4. The participant has a history of cancer.
5. 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.
6. The participant has or has had medical conditions that is/are considered clinically relevant in the context of the study.
7. The participant has one or more clinically significant out-of-range vital signs at the Screening or Baseline (Randomization) Visit.
8. The participant has a current diagnosis of viral hepatitis or a history of liver disease.
9. The participant has a known history of hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), or human immunodeficiency virus (HIV), unless the participant has a CD4+ count >200 and undetectable viral load.
10. The participant has a history of severe drug allergy or hypersensitivity or known hypersensitivity or intolerance to the excipients in rimegepant. History of anaphylaxis, documented hypersensitivity reaction, or clinically significant reaction to any drug.
11. Clinically significant abnormality identified on the medical or laboratory evaluation. The following laboratory results are exclusionary: • Serum creatinine value >1.5 times the upper limit of the reference range (ULN). • Serum total bilirubin > ULN, unless the participant has known or suspected Gilbert’s syndrome. • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 x ULN. AST and/or ALT may be repeated once during the screening period for assessment of eligibility.
12. Any “yes” response on the Columbia-Suicide Severity Rating Scale (C-SSRS) for the period of 30 days prior to Screening.
13. 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 study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change from baseline (observation period, OP) in the number of migraine days per month over the entire DBT phase (Weeks 1 to 12) in adolescents with episodic migraine.

Secondary endpoints 4

1. Percentage of participants with ≥50% reduction from the OP in the number of moderate to severe migraine days per month over the entire DBT phase in adolescents with episodic migraine.
2. Mean change from the OP in the number of moderate to severe headache days per month over the entire DBT phase in adolescents with episodic migraine.
3. Mean change from the OP in the number of migraine days per month in the first 4 weeks (Weeks 1 to 4) of the DBT phase in adolescents with episodic migraine.
4. Mean change from baseline in the Pediatric Quality of Life (PedsQLTM) total score at Week 12 of the DBT phase in adolescents with episodic migraine.

Investigational products

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

Test 4

Placebo 1

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

Adam Schayowitz

Public contact point

Organisation

Pfizer Inc.

Contact name

Adam Schayowitz

Third parties 10

Locations

4 EU/EEA countries · 27 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 195 files

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

Application history

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