Clinical trial NCT05125302: Study to Assess Adverse Events and Disease Activity of Oral Ubrogepant Tablets for the Acute Treatment of Migraine in Children and Adolescents (Ages 6-17)
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Single-attack Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Oral Ubrogepant in the Acute Treatment of Migraine With or Without Aura in Children and Adolescents (Ages 6-17)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Migraine
Keywords: Migraine
Ubrogepant
Ubrelvy
PERISCOPE
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2021-11-18
Enrollment: 1059
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Migraine is a common neurological disorder typically characterized by attacks of throbbing, moderate to severe headache, often associated with nausea, vomiting, and sensitivity to light and sound. Migraine is extremely common and disabling in children. The purpose of this study is to evaluate how safe and effective ubrogepant is in the acute treatment of migraine in children and adolescents.

Ubrogepant is a drug approved for the acute treatment of migraine in adults. Children and adolescents (aged 6-17 years) with a history of migraine will be enrolled. The study will include 2 cohorts of participants - PK Cohort and Main Study (non-PK cohort). Participants aged 6-11 years in the PK Cohort will receive Dose A or Dose B of Ubrogepant for PK analysis to determine dose selection for the main study. In the main study, after dose selection, children aged 6-11 years will be randomized to receive either low or high dose of Ubrogepant or placebo. There is a 1 in 3 chance that a participant will be assigned to placebo. Adolescents aged 12-17 years will be randomized to receive either low or high dose of Ubrogepant or placebo with a 1 in 3 chance of placebo assignment.

For qualifying migraine attacks, participants will receive oral tablets of the double-blind study intervention. There will be an option to take a second dose of double-blind study intervention (identical to initial dose), or rescue medication, at least 2 hours after the initial dose, for headache of moderate/severe intensity. Around 1059 participants will be enrolled in the study in approximately 120 sites in the United States. The study duration will be up to 6 months.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.


Eligibility criteria: Inclusion Criteria:

* A history of migraine with or without aura consistent with a diagnosis according to the International Classification of Headache Disorders (ICHD-3) for at least 6 months.
* By history, the participant's migraines typically last between 3 and 72 hours if untreated or treated unsuccessfully and migraine episodes are separated by at least 48 hours of headache pain freedom.
* History of 1 to 14 migraine attacks per month with moderate to severe headache in each of the 2 months prior to screening (Visit 1).
* Current or past use of at least 1 oral medication (over-the-counter medication or prescription medication) for the acute treatment of migraine.
* For main study participants, treatment of a qualifying migraine with single-blind placebo during the screening period and completion of 2-hour headache pain assessment.
* Weight is ≥ 20 kg (44 pounds) and \< 135 kg (298 pounds)
* Per investigator judgment, participant is able to swallow or can learn to swallow study intervention.
* The participant is able to understand and complete the study questionnaires and eDiary. Participants who need assistance with reading the assessments may be assisted by a parent or guardian.

Exclusion Criteria:

* Any clinically significant hematologic, endocrine, pulmonary, renal, hepatic, gastrointestinal, cardiovascular or neurologic disease.
* In the opinion of the investigator, other confounding pain syndromes, confounding psychiatric conditions, or other significant neurological disorders other than migraine.
* History of malignancy in the 5 years prior to Visit 1.
* History of any prior gastrointestinal conditions (eg, diarrhea syndromes, inflammatory bowel disease) that may affect the absorption or metabolism of the study intervention.
* Significant risk of self-harm, based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale (C-SSRS), or of harm to others; participants must be excluded if they report suicidal ideation with intent, with or without a plan, (ie, Type 4 or 5 on the C-SSRS) in the past 6 months or report suicidal behavior in the last 6 months prior to Visit 1 or Visit 2 assessments.
* At Visit 1, current alcohol or drug abuse or dependence per investigator's judgment.
* For main study participants, no headache at the 2-hour post dose assessment after taking single-blind placebo for a qualifying migraine during screening period (ie, placebo responder).
* A current diagnosis of chronic migraine as defined by ICHD-3
* Participants who overuse medication for migraine defined as use of opioids or barbiturates \> 2 days/month, triptans or ergots ≥ 10 days/month, simple analgesics (eg, aspirin, NSAIDs, acetaminophen) ≥ 15 days/month or any combination of triptans, ergots, or simple analgesics (eg, aspirin, NSAIDs, acetaminophen) ≥ 10 days/month in the 3 months prior to Visit 1 per investigator's judgment.
* Difficulty distinguishing migraine headache from tension-type or other headaches.
* Has a history of migraine aura with diplopia or impairment of level of consciousness, hemiplegic migraine, or retinal migraine as defined by ICHD-3.
* Has a current diagnosis of new persistent daily headache, trigeminal autonomic cephalgia (eg, cluster headache), or painful cranial neuropathy as defined by ICHD-3
* Required in-hospital (excluding emergency department visits) treatment for migraines 3 or more times in the 6 months prior to Visit 1.
* Requirement for any medication (eg, barbiturates) or diet (eg, grapefruit juice) that is on the list of prohibited concomitant medications that cannot be discontinued or switched to an allowable, alternative medication at Visit 1.
* Previous exposure, within the last 6 months, to injectable monoclonal antibodies blocking the calcitonin gene-related peptide (CGRP) pathway
* History of hypersensitivity or clinically significant adverse reaction to a CGRP receptor antagonist or hypersensitivity to any component of the study interventions, ubrogepant or placebo.
* Currently participating or has participated in a study with an investigational compound or device within 30 days prior to Visit 1

Primary outcomes:
measure: Percentage of participants with Pain Freedom at 2 Hours After the Initial Dose in pediatric participants aged 6 to 17 years
timeFrame: 2 hours after initial dose
Secondary outcomes:
measure: Percentage of participants with Pain Freedom at 2 Hours After the Initial Dose in pediatric participants aged 12 to 17 years
timeFrame: 2 hours after initial dose
measure: Percentage of participants with Pain Relief at 2 Hours After the Initial Dose in pediatric participants aged 12 to 17 years
timeFrame: 2 hours after initial dose
measure: Percentage of Participants With Sustained Pain Freedom From 2 to 24 Hours After Initial Dose in pediatric participants aged 6 to 17 years
timeFrame: 2 to 24 hours after initial dose
measure: Percentage of participants that used rescue medication (including a second dose of study intervention) within 24 hours after the initial dose in pediatric participants aged 6 to 17 years
timeFrame: 24 hours after initial dose
measure: Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose in pediatric participants aged 6 to 17 years
timeFrame: Baseline (Predose) to 2 hours after initial dose
measure: Percentage of Participants With Absence of the Most Bothersome Migraine-Associated Symptom Identified at Baseline at 2-Hours After Initial Dose in pediatric participants aged 12 to 17 years
timeFrame: Baseline (Predose) to 2 hours after initial dose
measure: Percentage of participants with Pain Freedom at 2 Hours After the Initial Dose in pediatric participants aged 6 to 11 years
timeFrame: 2 hours after initial dose
measure: Percentage of Participants With the Absence of Photophobia at 2 Hours After the Initial Dose in pediatric participants aged 6 to 17 years
timeFrame: 2 hours after initial dose
measure: Percentage of Participants With the Absence of Phonophobia at 2 Hours After the Initial Dose in pediatric participants aged 6 to 17 years
timeFrame: 2 hours after initial dose
measure: Percentage of Participants With the Absence of Nausea at 2 Hours After the Initial Dose in pediatric participants aged 6 to 17 years
timeFrame: 2 hours after initial dose
measure: Number of Participants with Adverse Events (AE)
timeFrame: Up to 6 months
measure: Percentage of Participants with Abnormal Change in Clinical Laboratory Test Results Like Hematology will be Assessed in pediatric participants aged 6 to 17 years
timeFrame: Up to 6 months
measure: Change From Baseline in Electrocardiograms (ECGs) in pediatric participants aged 6 to 17 years
timeFrame: Up to 6 months
measure: Percentage of Participants with Abnormal Change From Baseline in Vital Sign Measurements in pediatric participants aged 6 to 17 years
timeFrame: Up to 6 months
measure: Percentage of patients with suicidal ideation or suicidal behavior
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Rehabilitation & Neurological Services /ID# 229969
state: Alabama
city: Saraland
country: United States
facility: The Center for Clinical Trials - Saraland /ID# 231546
state: Alabama
city: Little Rock
country: United States
facility: Preferred Research Partners /ID# 230725
state: Arkansas
city: Anaheim
country: United States
facility: Advanced Research Center /ID# 227962
state: California
city: Fresno
country: United States
facility: Neuro Pain Medical Center /ID# 227966
state: California
city: Long Beach
country: United States
facility: Alliance for Research Alliance for Wellness /ID# 230546
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles /ID# 230596
state: California
city: Oceanside
country: United States
facility: Excell Research, Inc /ID# 230899
state: California
city: San Diego
country: United States
facility: Paradigm Clinical Research - San Diego /ID# 269608
state: California
city: San Jose
country: United States
facility: Lumos Clinical Research Center /ID# 231267
state: California
city: Upland
country: United States
facility: Pacific Clinical Research Management Group /ID# 231636
state: California
city: Walnut Creek
country: United States
facility: Sunwise Clinical Research /ID# 230971
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado - Aurora /ID# 231879
state: Colorado
city: Centennial
country: United States
facility: IMMUNOe Research Centers /ID# 230879
state: Colorado
city: Colorado Springs
country: United States
facility: MCB Clinical Research Centers /ID# 231625
state: Colorado
city: Stamford
country: United States
facility: New England Institute for Clinical Research /ID# 230635
state: Connecticut
city: Washington
country: United States
facility: Emerson Clinical Research Inst /ID# 231693
state: District of Columbia
city: Boynton Beach
country: United States
facility: Encore Medical Research of Boynton Beach LLC /ID# 246833
state: Florida
city: Fort Myers
country: United States
facility: Gulf Coast Clinical Research Center /ID# 230020
state: Florida
city: Gainesville
country: United States
facility: Sarkis Clinical Trials /ID# 227956
state: Florida
city: Gulf Breeze
country: United States
facility: Northwest Florida Clinical Research Group, LLC /ID# 231069
state: Florida
city: Hialeah
country: United States
facility: A.G.A Clinical Trials /ID# 230554
state: Florida
city: Hollywood
country: United States
facility: Encore Medical Research /ID# 245682
state: Florida
city: Homestead
country: United States
facility: Advanced Research Institute of Miami /ID# 230292
state: Florida
city: Lakeland
country: United States
facility: Auzmer Research /ID# 239251
state: Florida
city: Miami
country: United States
facility: Columbus Clinical Services, Llc /Id# 230880
state: Florida
city: Miami
country: United States
facility: My Preferred Research LLC /ID# 227886
state: Florida
city: Miami
country: United States
facility: Neurology & Pain Medicine /ID# 240168
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida /ID# 231632
state: Florida
city: Orlando
country: United States
facility: Clinical Associates of Orlando, LLC /ID# 272619
state: Florida
city: Palm Harbor
country: United States
facility: Suncoast Clinical Research - Palm Harbor /ID# 229337
state: Florida
city: Spring Hill
country: United States
facility: Asclepes Research Centers - Spring Hill /ID# 229815
state: Florida
city: Tampa
country: United States
facility: University of South Florida- Neuroscience Institute /ID# 229324
state: Florida
city: Weston
country: United States
facility: Encore Medical Research - Weston /ID# 246809
state: Florida
city: Winter Park
country: United States
facility: Pediatric Neurology and Epilepsy Specialists /ID# 229967
state: Florida
city: Atlanta
country: United States
facility: Treken Primary Care /ID# 240586
state: Georgia
city: Atlanta
country: United States
facility: Rare Disease Research, LLC /ID# 231046
state: Georgia
city: Atlanta
country: United States
facility: Clinical Integrative Research Center of Atlanta (CIRCA) /ID# 231134
state: Georgia
city: Brunswick
country: United States
facility: Coastal Georgia Child Neurology /ID# 231409
state: Georgia
city: Decatur
country: United States
facility: CenExcel iResearch LLC /ID# 227903
state: Georgia
city: Savannah
country: United States
facility: Velocity Clinical Research - Savannah /ID# 228992
state: Georgia
city: Stockbridge
country: United States
facility: Sleep Care Research Institute d/b/a Clinical Research Institute /ID# 231738
state: Georgia
city: Meridian
country: United States
facility: Velocity Clinical Research - Boise /ID# 231871
state: Idaho
city: Chicago
country: United States
facility: Chicago Headache Center & Research Institute /ID# 248625
state: Illinois
city: Ames
country: United States
facility: Accellacare - McFarland Clinic /ID# 229789
state: Iowa
city: Overland Park
country: United States
facility: College Park Family Care Center Overland Park /ID# 231456
state: Kansas
city: Overland Park
country: United States
facility: Psychiatric Associates /ID# 230872
state: Kansas
city: Wichita
country: United States
facility: Alliance for Multispecialty Research (AMR) - Wichita West /ID# 234126
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Chandler Medical Center /ID# 230827
state: Kentucky
city: Baltimore
country: United States
facility: Pharmasite Research, Inc. /ID# 227908
state: Maryland
city: Burnsville
country: United States
facility: Minneapolis Clinic of Neurology - Burnsville /ID# 232551
state: Minnesota
city: Petal
country: United States
facility: MediSync Clinical Research Hattiesburg Clinic /ID# 233326
state: Mississippi
city: Ridgeland
country: United States
facility: Proven Endpoints LLC /ID# 239513
state: Mississippi
city: Ozark
country: United States
facility: Sharlin Health Neuroscience Research Center /ID# 229523
state: Missouri
city: Papillion
country: United States
facility: Cognitive Clinical Trials (CCT) - Papillion /ID# 232552
state: Nebraska
city: Nashua
country: United States
facility: Healthy Perspectives - Innovative Mental Health Services, PLLC /ID# 230312
state: New Hampshire
city: Annandale
country: United States
facility: Hunterdon Neurology /ID# 245648
state: New Jersey
city: Morristown
country: United States
facility: Goryeb Children's Hospital /ID# 229507
state: New Jersey
city: Runnemede
country: United States
facility: CVS HealthHUB - Runnemede /ID# 234233
state: New Jersey
city: Amherst
country: United States
facility: Dent Neurologic Institute - Amherst /ID# 231182
state: New York
city: Mount Kisco
country: United States
facility: Bioscience Research /ID# 232159
state: New York
city: New York
country: United States
facility: Modern Migraine MD /ID# 258081
state: New York
city: Port Jefferson Station
country: United States
facility: North Suffolk Neurology /ID# 230956
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University /ID# 239898
state: New York
city: Charlotte
country: United States
facility: CVS HealthHUB - Charlotte /ID# 239530
state: North Carolina
city: Hickory
country: United States
facility: OnSite Clinical Solutions, LLC - Hickory /ID# 227994
state: North Carolina
city: Cincinnati
country: United States
facility: Patient Priority Clinical Sites, LLC /ID# 238485
state: Ohio
city: Cincinnati
country: United States
facility: University Of Cincinnati Medical Center /ID# 231199
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center /ID# 244689
state: Ohio
city: Cincinnati
country: United States
facility: Headache Center of Hope /ID# 242645
state: Ohio
city: Columbus
country: United States
facility: Centricity Research Columbus /ID# 231181
state: Ohio
city: West Chester
country: United States
facility: CincyScience /ID# 230046
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company /ID# 227961
state: Oklahoma
city: Portland
country: United States
facility: Providence Brain and Spine Institute /ID# 231607
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia - Main /ID# 232487
state: Pennsylvania
city: Scottdale
country: United States
facility: Frontier Clinical Research, LLC - Scottdale /ID# 231913
state: Pennsylvania
city: Smithfield
country: United States
facility: Frontier Clinical Research - Smithfield /ID# 231912
state: Pennsylvania
city: Charleston
country: United States
facility: Coastal Pediatric Research /ID# 238616
state: South Carolina
city: Greenville
country: United States
facility: Tribe Clinical Research LLC /ID# 230422
state: South Carolina
city: Greer
country: United States
facility: Duplicate_Premier Neurology, P.C. /ID# 227999
state: South Carolina
city: Nashville
country: United States
facility: Access Clinical Trials, Inc. /ID# 228002
state: Tennessee
city: Austin
country: United States
facility: UT Health Austin at Dell Children's Neurology Clinic /ID# 244266
state: Texas
city: Austin
country: United States
facility: BioBehavioral Research of Austin /ID# 230529
state: Texas
city: Austin
country: United States
facility: Velocity Clinical Research, Austin /ID# 230557
state: Texas
city: Beaumont
country: United States
facility: Tekton Research - Beaumont /ID# 231207
state: Texas
city: Dallas
country: United States
facility: Relaro Medical Trials /ID# 239642
state: Texas
city: Dallas
country: United States
facility: Cedar Health Research /ID# 228003
state: Texas
city: El Paso
country: United States
facility: 3A Research - East El Paso /ID# 239193
state: Texas
city: Friendswood
country: United States
facility: Earle Research /ID# 231548
state: Texas
city: Houston
country: United States
facility: DM Clinical Research /ID# 229826
state: Texas
city: Houston
country: United States
facility: Houston Clinical Research Associates /ID# 244889
state: Texas
city: Kerrville
country: United States
facility: Sante Clinical Research /ID# 246503
state: Texas
city: Lampasas
country: United States
facility: FMC Science /ID# 231915
state: Texas
city: Mansfield
country: United States
facility: Livingspring Family Medical Center /ID# 249869
state: Texas
city: Plano
country: United States
facility: AIM Trials /ID# 230142
state: Texas
city: San Antonio
country: United States
facility: Road Runner Research /ID# 230527
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of The Woodlands /ID# 230163
state: Texas
city: Waxahachie
country: United States
facility: ClinPoint Trials /ID# 230295
state: Texas
city: Bountiful
country: United States
facility: Pantheon Clinical Research /ID# 250703
state: Utah
city: Salt Lake City
country: United States
facility: Highland Clinical Research /ID# 239362
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Health Hospital /ID# 230908
state: Utah
city: Woodstock
country: United States
facility: Neuropsychiatric Associates LLC/DBA Woodstock Research Center /ID# 238976
state: Vermont
city: Franklin
country: United States
facility: Office of Maria Ona /ID# 234232
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters - Children's Medical Tower /ID# 230581
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research /ID# 231320
state: Virginia
city: Everett
country: United States
facility: Core Clinical Research /ID# 227904
state: Washington
city: Kingwood
country: United States
facility: Frontier Clinical Research - Kingwood /ID# 231914
state: West Virginia
city: Mequon
country: United States
facility: Mind+ Neurology /ID# 275529
state: Wisconsin
city: Bayamon
country: Puerto Rico
facility: Clinical Research Investigator Group, LLC /ID# 267454
city: Dorado
country: Puerto Rico
facility: Puerto Rico Health Institute /ID# 249162
city: San Juan
country: Puerto Rico
facility: GCM Medical Group PSC /ID# 249643
city: San Juan
country: Puerto Rico
facility: Caribbean Medical Research Center /ID# 265301
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: