E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Migraine (with or without aura) |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052787 |
E.1.2 | Term | Migraine without aura |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027607 |
E.1.2 | Term | Migraine with aura |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10027603 |
E.1.2 | Term | Migraine headaches |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 reduction from baseline in the mean number of migraine days per month over the entire course of the double-blind treatment phase. |
|
E.2.2 | Secondary objectives of the trial |
● To compare the efficacy of rimegepant to placebo on the proportion of subjects that have at least a 50% reduction from baseline in the mean number of moderate to severe migraine days per month over the entire course of the double-blind treatment phase in adolescents with episodic migraine. ● To compare the efficacy of rimegepant to placebo on the reduction from baseline in the mean number of migraine days per month in the first 4 weeks of the double-blind treatment phase in adolescents with episodic migraine. ● To compare the change from baseline in the Pediatric Quality of Life (PedsQLTM) 4.0 Generic Core Scales total score at Week 12 of the double-blind treatment phase between rimegepant and placebo in adolescents with episodic migraine. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria: 1. Subject has at least a 6 month history of migraine (with or without aura) and including the following: a. 14 or less headache days per month during the 3 month period prior to the Screening Visit b. 6 or more migraine days during the Observation Period c. 14 or less headache days during the Observation Period d. Pediatric Migraine Disability Assessment Scale (PedMIDAS) Disability Score of >10 to ≤50, indicating mild (score of 11 to 30) or moderate (score of 31 to 50) disruption in daily activities, as assessed at the Baseline (Randomization) Visit e. Ability to verbally distinguish migraine attacks from tension/cluster or other types of headaches f. Migraine attacks, on average, lasting 4 - 72 hours if untreated g. Subjects 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. Male and female subjects ≥ 6 to <18 years; subjects must be less than 18 at the time of signing assent / consent. 3. Subjects must have a weight of ≥40 kg (child cohort requirement ≥15 kg) at the Screening Visit. |
|
E.4 | Principal exclusion criteria |
Exclusion criteria: 1. Subjects with a history of basilar migraine, cluster headaches, or hemiplegic migraine 2. The subject has a continuous migraine (defined as an unrelenting headache) within 1 month prior to Screening Visit. 3. The subject has a history or diagnosis of complications of migraine 4. The subject has a confounding and clinically significant pain syndrome that may interfere with the subject's ability to participate in this study. 5. The subject has any current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6 months prior to the Screening Visit. Subjects with a lifetime history of psychosis and/or mania are excluded. 6. History of suicidal behavior or the subject is at risk of self-harm or harm to others. 7. History of major psychiatric disorder. 8. The subject has a current diagnosis or history of substance abuse 9. The subject 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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline (observation period) in the mean number of migraine days per month over the entire course (Weeks 1 to 12) of the double-blind treatment phase in adolescents with episodic migraine |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoints for evaluation of Primary EndPoint: over the entire course (Weeks 1 to 12) of the double-blind treatment phase |
|
E.5.2 | Secondary end point(s) |
Key Secondary Endpoints: ● Achievement of at least a 50% reduction from baseline in the mean number of moderate to severe migraine days per month over the entire course of the double-blind treatment phase in adolescents with episodic migraine. ● Change from baseline in the mean number of migraine days per month in the first 4 weeks (Weeks 1 through 4) of the double-blind treatment phase in adolescents with episodic migraine. ● The mean change from baseline in the Pediatric Quality of Life (PedsQL) total score at Week 12 of the double-blind treatment phase in adolescents with episodic migraine. Refer to Protocol for full list of Secondary endpoints |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints for evaluation of Key Secondary Endpoints: ● Achievement of at least a 50% reduction from baseline in the mean number of moderate to severe migraine days per month over the entire course of the double-blind treatment phase in adolescents with episodic migraine. ● Change from baseline in the mean number of migraine days per month in the first 4 weeks (Weeks 1 through 4) of the double-blind treatment phase in adolescents with episodic migraine. ● The mean change from baseline in the PedsQL total score at Week 12 of the double-blind treatment phase in adolescents with episodic migraine. For timepoints for all the other secondary endpoints please refer to the Protocol |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
There is an optional open-label, extension phase following the double-blind, treatment phase |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United Kingdom |
United States |
France |
Italy |
Poland |
Spain |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |