Ubrogepant treatmeNt in mIgraine Patients Utilizing mOnoclonal aNtibodies (UNION)

Ubrogepant Efficacy and Safety in the Treatment of Acute Migraine in Patients Currently Treated With CGRP Monoclonal Antibodies (CGRPmAbs)

This is a prospective open-label randomized study assessing similar endpoints included in the pivotal trial for ubrogepant, which are pain freedom and freedom from the most bothersome symptom at two hours. Patients between 18-75 years old with a one-year history of migraine who experience ≥3 migraine days/month will be screened. This study will include migraine patients treated with or without injectable CGRPmAbs. As was the case in the clinical trials, this will be a single-attack study. Patients will be randomized to treat a single migraine attack with ubrogepant 50mg or 100mg. Patients will record dosing time, most bothersome symptom (nausea, photophobia, or phonophobia - chosen by patient), pain freedom, pain relief, the use of a 2nd dose if required, and adverse reactions. Patients will follow up within 30 days post treatment. Patients will be assessed for adverse events, and the safety data will be compared with the original clinical trial.

Study Overview

• Status: Recruiting
• Conditions: Headache, Migraine
• Intervention / Treatment: Drug: Ubrogepant 50 MG [Ubrelvy]; Drug: Ubrogepant 100 MG [Ubrelvy]

Detailed Description

The purpose of this study is to examine the safety and efficacy of ubrogepant (UBRELVY) in patients currently treated with one of the injectable monoclonal antibodies targeting CGRP or the CGRP receptor (Aimovig, Ajovy, or Emgality). There are currently very limited data available about the use of CGRP receptor antagonists in this population, resulting in difficulty obtaining prior authorization to use ubrogepant in patients currently treated with CGRPmAbs. Questions remain as to whether these patients, whose CGRP or CGRP receptors are suppressed, will experience the same safety and efficacy results as patients without such suppression by CGRPmAbs.

This is a prospective open-label randomized study assessing similar endpoints included in the pivotal trial for ubrogepant, which are pain freedom and freedom from the most bothersome symptom at two hours. Patients between 18-75 years old with a one-year history of migraine who experience ≥3 migraine days/month will be screened. This study will include migraine patients treated with or without injectable CGRPmAbs. As was the case in the clinical trials, this will be a single-attack study. Patients will be randomized to treat a single migraine attack with ubrogepant 50mg or 100mg. Patients will record dosing time, most bothersome symptom (nausea, photophobia, or phonophobia - chosen by patient), pain freedom, pain relief, the use of a 2nd dose if required, and adverse reactions. Patients will follow up within 30 days post treatment. Patients will be assessed for adverse events, and the safety data will be compared with the original clinical trial.

Primary Objective:

To evaluate the safety and efficacy of ubrogepant (UBRELVY) in patients currently treated with one of the injectable monoclonal antibodies targeting CGRP or the CGRP receptor (Aimovig, Ajovy, or Emgality).

Primary Endpoint:

• Pain freedom at 2 hours.
• Freedom from most bothersome symptom at 2 hours

Secondary Objectives:

To assess improvements with the addition of ubrogepant (UBRELVY) in patients currently treated with one of the injectable monoclonal antibodies targeting CGRP or the CGRP receptor (Aimovig, Ajovy, or Emgality).

Secondary Endpoint:

• Pain relief at 2 hours (this is different from pain freedom: moderate to severe pain reduced to mild or no pain)
• Percentage of patients with sustained pain relief from 2-24 hours after initial dose
• Percentage of patients with sustained pain freedom from 2-24 hours after initial dose
• Pain relief at 2 hours after 2nd dose
• Percentage of patients with sustained pain relief from 2-24 hours after 2nd dose
• Percentage of patients with sustained pain freedom from 2-24 hours after 2nd dose

• Study Type: Interventional
• Enrollment (Estimated): 164
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Melody Smith; Phone Number: 7739351000; Email: msmith@chicagoheadache.com
• Study Contact Backup: Name: Megan Helle; Phone Number: 7739351000; Email: mhelle@chicagoheadache.com

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60657
      • Recruiting
      • Chicago Headache Center & Research Institute
      • Contact: Megan Helle; Phone Number: 7739351000; Email: mhelle@chicagoheadache.com
      • Contact: Melody Smith; Phone Number: 773-935-1000; Email: msmith@chicagoheadache.com
      • Principal Investigator: Bradley Torphy, MD
    • Naperville, Illinois, United States, 60563
      • Recruiting
      • Chicago Headache Center & Research Institute
      • Contact: Megan Helle; Phone Number: 7739351000; Email: mhelle@chicagoheadache.com
      • Contact: Melody Smith; Phone Number: 773-935-1000; Email: msmith@chicagoheadache.com
      • Principal Investigator: Bradley Torphy, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female patients ages 18 to 75 years, at screening (Visit 1).
• At least a 1-year history of migraine with or without aura.
• History of ≥3 monthly headache days of at least moderate severity.
• Study patient currently on CGRPmAbs must be on treatment > 1 month at screening.
• By history, the patient's migraines typically last between 4 and 72 hours if untreated or treated unsuccessfully and migraine episodes are separated by at least 48 hours of headache pain freedom

Exclusion Criteria:

• History of <3 monthly headache days of at least moderate severity
• Concomitant use of strong CYP3A4 inducers (e.g., phenytoin, barbiturates, rifampin, St. John's Wort)
• Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin)
• Currently on Botox treatment for CM.
• Concomitant use of gepants as a preventative treatment.
• Current user of illicit drugs, or a history within 1 year prior to screening (visit 1) of drug or alcohol abuse or dependence
• Clinically significant hematologic, endocrine, cardiovascular, pulmonary, gastrointestinal, or neurologic disease. If there is a history of such a disease, but the condition has been stable for more than 1 year prior to screening (visit 1) and is judged by the PI as not likely to interfere with participation in the study, the participant may be included.
• Woman is pregnant, planning to become pregnant during the course of the study, or currently lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: w/o CGRPmAb	Drug: Ubrogepant 50 MG [Ubrelvy]; Ubrogepant 50 MG [Ubrelvy]; Drug: Ubrogepant 100 MG [Ubrelvy]; Ubrogepant 100 MG [Ubrelvy]
Active Comparator: Tx w/ CGRPmAb	Drug: Ubrogepant 50 MG [Ubrelvy]; Ubrogepant 50 MG [Ubrelvy]; Drug: Ubrogepant 100 MG [Ubrelvy]; Ubrogepant 100 MG [Ubrelvy]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain freedom	Pain freedom at 2 hours.	2 hours post treatment
Freedom from most bothersome symptom	Freedom from most bothersome symptom at 2 hours.	2 hours post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain relief at 2 hours	Pain relief at 2 hours (this is different from pain freedom: moderate to severe pain reduced to mild or no pain).	2 hours post treatment
Percentage of patients with sustained pain relief from 2-24 hours after initial dose.	Percentage of patients with sustained pain relief from 2-24 hours after initial dose.	2-24 hours after initial dose
Percentage of patients with sustained pain freedom from 2-24 hours after initial dose.	Percentage of patients with sustained pain freedom from 2-24 hours after initial dose.	2-24 hours after initial dose
Pain relief at 2 hours after 2nd dose	Pain relief at 2 hours after 2nd dose.	2 hours after 2nd dose
Percentage of patients with sustained pain relief from 2-24 hours after 2nd dose.	Percentage of patients with sustained pain relief from 2-24 hours after 2nd dose.	2-24 hours after 2nd dose
Percentage of patients with sustained pain freedom from 2-24 hours after 2nd dose.	Percentage of patients with sustained pain freedom from 2-24 hours after 2nd dose.	2-24 hours after 2nd dose

Collaborators and Investigators

• Sponsor: Chicago Headache Center & Research Institute
• Collaborators: AbbVie
• Investigators: Principal Investigator: Bradley Torphy, MD, Chicago Headache Center & Research Institute

Publications and helpful links

General Publications

• Dodick DW, Lipton RB, Ailani J, Halker Singh RB, Shewale AR, Zhao S, Trugman JM, Yu SY, Viswanathan HN. Ubrogepant, an Acute Treatment for Migraine, Improved Patient-Reported Functional Disability and Satisfaction in 2 Single-Attack Phase 3 Randomized Trials, ACHIEVE I and II. Headache. 2020 Apr;60(4):686-700. doi: 10.1111/head.13766. Epub 2020 Feb 19.

Helpful Links

• Chicago Headache Center & Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: August 14, 2022
• First Submitted That Met QC Criteria: August 14, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache
• Other Study ID Numbers: 2020-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes