Lu AG09222 + Ubrogepant for Migraine

Recruiting at 4 trial locations

Overseen By Email contact via H. Lundbeck A/S

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lundbeck A/S

Must be taking: Ubrogepant

Must not be taking: Anti-PACAP treatments

Disqualifiers: Pregnancy, Breastfeeding, Recent clinical trial, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The main goal of this trial is to learn more about the safety and tolerability of Lu AG09222 when taken together with ubrogepant. This includes looking for any new or worsening medical issues the participants have with the treatment. During the trial, participants with migraine will receive ubrogepant oral tablets and an injection of either Lu AG09222 or a placebo.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. However, if you have taken any investigational medicinal product in the last 3 months or less than 5 half-lives of that product, you may not be eligible to participate.

What data supports the effectiveness of the drug Lu AG09222 + Ubrogepant for treating migraines?

Ubrogepant has been shown to be effective in treating migraines, as it helps reduce pain and other bothersome symptoms within two hours of taking the medication. It is approved by the FDA for this use, and studies have confirmed its safety and effectiveness in real-world settings. ^{1 2 3 4 5}

Is the combination of Lu AG09222 and Ubrogepant safe for humans?

Ubrogepant has been shown to be generally safe for treating migraines in several studies, including long-term trials, but its safety when combined with other treatments like Lu AG09222 has not been specifically evaluated. ^{1 3 6 7 8}

How is the drug Lu AG09222 + Ubrogepant unique for treating migraines?

The combination of Lu AG09222 and ubrogepant is unique because it potentially combines two different mechanisms to treat migraines, with ubrogepant being a known oral medication that blocks the action of a protein involved in migraine attacks. This combination could offer a novel approach compared to existing treatments that typically use a single mechanism. ^{1 2 3 7 9}

Research Team

Email contact via H. Lundbeck A/S

Principal Investigator

H. Lundbeck A/S

Eligibility Criteria

This trial is for individuals with migraines, as defined by ICHD-3 guidelines, who've had this condition for at least a year. They should experience 2 or more migraine days monthly but less than 15 headache days per month over the last three months. Participants must have a BMI between 18.5 and ≤35 kg/m².

Inclusion Criteria

Participant has a body mass index (BMI) ≥18.5 and ≤35 kilograms per meter squared (kg/m^2) at the Screening Visit

I have had migraines for at least a year.

I have been diagnosed with migraine according to ICHD-3 guidelines.

Exclusion Criteria

Participant has participated in a clinical trial <30 days prior to the Screening Visit

Participant has taken any investigational medicinal product (IMP) <3 months or <5 half-lives of that product, whichever is longer, prior to Visit 1

Participant has known or suspected hypersensitivity or intolerance to the IMP, auxiliary medicinal product (AxMP), or their excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 doses of ubrogepant, followed by either Lu AG09222 or placebo, and additional doses of ubrogepant

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lu AG09222

Trial Overview The study aims to assess the safety of Lu AG09222 when used with ubrogepant in people with migraines. It involves taking ubrogepant tablets and getting injections of either Lu AG09222 or a placebo to see if there are any health changes.

Participant Groups

Group I: Ubrogepant with Lu AG09222 Experimental Treatment 2 Interventions

Participants will receive 2 doses of ubrogepant, then participants will receive Lu AG09222 followed by additional doses of ubrogepant.

Group II: Ubrogepant with Placebo Placebo Group 2 Interventions

Participants will receive 2 doses of ubrogepant, then participants will receive placebo followed by additional doses of ubrogepant.

Who Is Running the Clinical Trial?

H. Lundbeck A/S

Lead Sponsor

Trials

332

Recruited

78,300+

Charl van Zyl

H. Lundbeck A/S

Chief Executive Officer since 2023

Degree in Medical Biochemistry from the University of Cape Town, South Africa

Johan Luthman

H. Lundbeck A/S

Chief Medical Officer since 2019

MD from the University of Gothenburg, Sweden

Findings from Research

In a 52-week trial involving 1230 participants, ubrogepant (50 mg and 100 mg) was found to be safe and well-tolerated for the acute treatment of migraines, with low rates of treatment-related adverse events (10% for 50 mg and 11% for 100 mg).

The most common side effect was upper respiratory tract infection, and there were no serious liver-related issues, indicating that ubrogepant does not significantly impact liver function, which is crucial for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety Evaluation of Ubrogepant for the Acute Treatment of Migraine: Phase 3, Randomized, 52-Week Extension Trial. Ailani, J., Lipton, RB., Hutchinson, S., et al.[2021]

In a phase 3 trial involving 808 participants and 19,291 migraine attacks, ubrogepant was significantly more effective in achieving pain freedom and reducing associated symptoms when administered during mild migraine pain compared to moderate or severe pain.

The treatment resulted in over double the rates of normal function at 2 hours post-treatment for both doses of ubrogepant (50 mg and 100 mg), with mild pain attacks showing much higher efficacy rates (47.1% and 55.2% for pain freedom, respectively).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Ubrogepant in the Acute Treatment of Migraine With Mild Pain vs Moderate or Severe Pain. Lipton, RB., Dodick, DW., Goadsby, PJ., et al.[2022]

Ubrogepant, a CGRP receptor antagonist approved by the FDA, has been shown to be effective in providing pain relief from migraines, outperforming placebo in Phase III trials (ACHIEVE I and II) within 2 hours of administration.

The 52-week open label extension of these trials confirmed the safety of ubrogepant, although a real-world study indicated higher adverse event rates, highlighting the need for further research on its long-term safety and efficacy, especially when used with other CGRP therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ubrogepant in the Acute Management of Migraine: A Narrative Review. Chiang, CC., VanderPluym, JH.[2021]

Ubrogepant (Ubrelvy™) is a highly-selective CGRP antagonist that was approved in December 2019 for the acute treatment of migraines in adults, marking a significant advancement in migraine therapy.

As an orally administered medication, ubrogepant offers a new option for adults suffering from migraines, providing a targeted mechanism of action that specifically blocks the CGRP pathway involved in migraine attacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ubrogepant: First Approval. Scott, LJ.[2020]

In a Phase 3 clinical trial involving 1686 participants, ubrogepant demonstrated significantly greater efficacy than placebo for acute migraine treatment, with 21.8% of patients achieving pain freedom at 2 hours after taking the 50 mg dose.

Ubrogepant 50 mg also resulted in a higher rate of absence of the most bothersome migraine-associated symptom compared to placebo, indicating its potential effectiveness in alleviating multiple aspects of migraine attacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine: The ACHIEVE II Randomized Clinical Trial. Lipton, RB., Dodick, DW., Ailani, J., et al.[2021]

A comprehensive analysis of 2,067 reports from the FDA Adverse Event Reporting System revealed that Ubrogepant, used for treating acute migraines, is associated with various adverse events, including nausea, dizziness, and new reports of hemiparesis and mental impairment.

The study highlights the importance of monitoring Ubrogepant's long-term safety, as it identified new adverse events not previously documented in clinical trials, enhancing our understanding of its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating Ubrogepant-related adverse events using the FDA adverse event reporting system. Cao, B., Gu, S., Shen, Z., et al.[2023]

Ubrogepant, a calcitonin gene-related peptide receptor antagonist, has been shown to be significantly more effective than placebo in providing relief from migraine pain within 2 hours, with odds ratios indicating strong efficacy at both 50 mg and 100 mg doses.

This medication is a safe and effective alternative for patients who cannot tolerate traditional migraine treatments like NSAIDs or triptans, making it an important option for those with limited treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ubrogepant: An Oral Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist for Abortive Migraine Treatment. Nedd, M., Garland, S., Falk, N., et al.[2022]

Ubrogepant is effective for treating acute migraine attacks, showing consistent efficacy across different cardiovascular disease risk categories in a pooled analysis of 3358 participants from the ACHIEVE trials.

The safety profile of ubrogepant was comparable to placebo, with no increase in treatment-emergent adverse events related to cardiovascular risk factors, indicating it is safe for use in patients with varying levels of cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of ubrogepant in participants with major cardiovascular risk factors in two single-attack phase 3 randomized trials: ACHIEVE I and II. Hutchinson, S., Silberstein, SD., Blumenfeld, AM., et al.[2021]

Ubrogepant significantly improves pain freedom and reduces bothersome migraine symptoms within 2 hours compared to placebo, with 20.8% of patients achieving pain freedom versus 12.6% for placebo in a meta-analysis of three trials involving 3326 patients.

Short-term use of ubrogepant does not increase the risk of treatment-related adverse events compared to placebo, indicating it is a safe option for acute migraine treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ubrogepant for the Acute Treatment of Episodic Migraine: A Meta-Analysis of Randomized Clinical Trials. Yang, Y., Chen, M., Sun, Y., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-Term Safety Evaluation of Ubrogepant for the Acute Treatment of Migraine: Phase 3, Randomized, 52-Week Extension Trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Ubrogepant in the Acute Treatment of Migraine With Mild Pain vs Moderate or Severe Pain. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Ubrogepant in the Acute Management of Migraine: A Narrative Review. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Ubrogepant: First Approval. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine: The ACHIEVE II Randomized Clinical Trial. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Evaluating Ubrogepant-related adverse events using the FDA adverse event reporting system. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Ubrogepant: An Oral Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist for Abortive Migraine Treatment. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of ubrogepant in participants with major cardiovascular risk factors in two single-attack phase 3 randomized trials: ACHIEVE I and II. [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ubrogepant for the Acute Treatment of Episodic Migraine: A Meta-Analysis of Randomized Clinical Trials. [2021]