Phase 3 Randomized Double-Blind Placebo-Controlled Trial Evaluating Rimegepant Efficacy and Safety in Acute Migraine Treatment in Pediatric Patients Aged 6-17 Years
- Trial ID
- 2024-512743-23-00
- Protocol
- C4951002
- Sponsor
- Pfizer Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of rimegepant compared with placebo in the acute treatment of **migraine** in the adolescent population, specifically those aged 12 to less than 18 years. This is measured by the achievement of pain freedom at 2 hours post-dose. The clinical relevance of this objective lies in addressing the need for effective acute migraine treatments in adolescents, a group for whom migraine can significantly impact daily functioning and quality of life.
Secondary objectives include:
- Evaluating the efficacy of rimegepant relative to placebo in the acute treatment of migraine in children and adolescents aged 6 to less than 18 years, as measured by pain freedom at 2 hours post-dose.
- Assessing rimegepant compared to placebo on freedom from the most bothersome symptom associated with migraine at 2 hours post-dose in the adolescent population.
- Evaluating the probabilities of requiring rescue medication within 24 and 48 hours of initial treatment in the adolescent population.
- Assessing sustained pain freedom from 2 to 24 hours and from 2 to 48 hours post-dose in the adolescent population.
- Evaluating 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.
- Assessing the efficacy of rimegepant relative to placebo in the acute treatment of migraine in children aged 6 to less than 12 years, as measured by pain freedom at 2 hours post-dose.
- Evaluating rimegepant relative to placebo on freedom from the most bothersome symptom associated with migraine at 2 hours post-dose in children and in the combined population of children and adolescents.
- Assessing the probabilities of requiring rescue medication within 24 and 48 hours of initial treatment in children and in the combined population of children and adolescents.
- Evaluating sustained pain freedom from 2 to 24 hours and from 2 to 48 hours post-dose in children and in the combined population of children and adolescents.
- Assessing freedom from photophobia, nausea, and pain relief at 2 hours post-dose in adolescents, children, and the combined population of children and adolescents.
- Evaluating the time to first report of pain relief in adolescents, children, and the combined population of children and adolescents.
Participants
The clinical trial involves a total of **1945 participants** who are adolescents aged **12 to less than 18 years**. The study population includes both male and female subjects, with a focus on evaluating the efficacy of rimegepant in the acute treatment of **migraine**. Participants were selected based on a history of migraine, with or without aura, for more than six months prior to screening, and experiencing 1 to 8 moderate or severe attacks per month. The trial includes individuals who are on stable doses of prophylactic migraine medication, excluding CGRP antagonists. Participants must have a body weight of over 15 kg, with specific weight requirements for those in EU countries. The trial population is characterized by their ability to distinguish between migraine and other types of headaches, and they must have adequate venous access for blood sampling. The study ensures that female participants of childbearing potential use effective contraceptive methods and have a confirmed negative pregnancy test. The trial does not include individuals with clinically significant abnormalities that could interfere with study procedures. The selection criteria ensure a representative sample of the adolescent population affected by migraine, providing valuable insights into the treatment's efficacy.
Plans and Procedures
The clinical trial is a **Phase 3**, multicenter, randomized, double-blind, group sequential, placebo-controlled study designed to evaluate the efficacy and safety of **rimegepant** for the treatment of **acute migraine** (with or without aura) in children and adolescents aged 6 to less than 18 years. The trial aims to assess the primary endpoint of pain freedom at 2 hours post-dose in the adolescent population, using a 4-point numeric rating scale. Secondary endpoints include pain freedom in the combined population of children and adolescents, freedom from the most bothersome symptom (MBS) associated with migraine, and the probability of requiring rescue medication within 24 and 48 hours post-treatment.
The trial is expected to last until February 15, 2025, with recruitment having started on January 8, 2021. Participants will be involved in the study for a maximum treatment period of 2 days. The study involves several visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as a history of migraine, age, and weight requirements. Participants will then proceed to the baseline visit, where they will be randomized to receive either rimegepant or placebo in the form of an oral lyophilisate. Follow-up visits will be conducted to monitor the participants' response to the treatment and to collect data on the primary and secondary endpoints. The end-of-study visit will conclude the trial, where final assessments will be made.
Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial is conducted under strict ethical guidelines, ensuring that all participants provide informed consent and assent, and that their health and well-being are prioritized throughout the study.
Treatment
The clinical trial involves the administration of **Rimegepant**, an experimental medication, in the form of an **oral lyophilisate**. The study utilizes two dosages of Rimegepant: 25 mg and 75 mg. The 25 mg oral lyophilisate is manufactured by Pfizer Inc. and is administered orally. The maximum daily dose for this formulation is 50 mg, with a total treatment period of up to 2 days. The 75 mg oral lyophilisate, marketed under the name VYDURA, is produced by Pfizer Europe MA EEIG. This formulation also has a maximum daily dose of 75 mg and a treatment period of up to 2 days. Both formulations are chemically derived and are intended for the acute treatment of **migraine** in adolescents aged 12 to less than 18 years.
In addition to the experimental treatments, the study includes the use of placebo controls. Two placebo formulations are utilized: one corresponding to the 25 mg Rimegepant and another to the 75 mg Rimegepant. These placebos are designed to match the appearance and administration route of the active treatments but do not contain any active pharmaceutical ingredients. The use of placebos is integral to maintaining the double-blind nature of the study, ensuring unbiased assessment of the efficacy and safety of Rimegepant.
Efficacy
The efficacy of **rimegepant** in the treatment of migraine in children and adolescents will be assessed through a Phase 3, multicenter, randomized, double-blind, placebo-controlled study. The primary endpoint for evaluating efficacy is pain freedom at 2 hours post-dose, measured using a 4-point numeric rating scale (0=none, 1=mild, 2=moderate, 3=severe) in the adolescent population aged 12 to less than 18 years. Secondary endpoints include pain freedom at 2 hours post-dose in the combined population of children and adolescents aged 6 to less than 18 years, assessed using both a 4-point numeric scale for adolescents and a 5-Face visual analogue scale (VAS) for children.
Additional secondary endpoints involve assessing freedom from the most bothersome symptom (MBS) associated with migraine, such as nausea, phonophobia, or photophobia, using a binary scale (0=absent, 1=present) at 2 hours post-dose. The study will also evaluate the probabilities of requiring rescue medication within 24 and 48 hours post-dose, sustained pain freedom from 2 to 24 and 2 to 48 hours post-dose, and the proportion of participants able to function normally at 2 hours post-dose using the Functional Disability scale. These assessments will be conducted in both the adolescent population and the combined population of children and adolescents.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- 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.
- 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
- 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.
- 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.
- 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
- 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).
- 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.
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Poland | Recruiting | 08 Jan 2021 | 67 |
 Spain | Recruiting | 08 Jan 2021 | 70 |
 Sweden | Recruiting | 08 Jan 2021 | 18 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
35 mg oral lyophilisate | Test | ORAL LYOPHILISATE | ORAL | 35 | 2 | PRD12679088 |
Placebo for 35 mg rimegepant | Placebo | N/A | — | — | — | N/A |
Placebo for 50 mg rimegepant | Placebo | N/A | — | — | — | N/A |
25 mg oral lyophilisate | Test | ORAL LYOPHILISATE | ORAL | 50 | 2 | PRD11292429 |
Placebo for 75 mg Rimegepant | Placebo | N/A | — | — | — | N/A |
50 mg oral lyophilisate | Test | ORAL LYOPHILISATE | ORAL | 50 | 2 | PRD11292436 |
VYDURA 75 mg oral lyophilisate | Test | ORAL LYOPHILISATE | ORAL | 75 | 2 | PRD10088770 |
Placebo for 25 mg Rimegepant | Placebo | N/A | — | — | — | N/A |