Lu AG09222 + Ubrogepant for Migraine

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of combining Lu AG09222 (an experimental treatment) with ubrogepant for individuals with migraines. Researchers aim to identify any new or worsening health issues when using these treatments together. Participants will receive either both treatments or a placebo (a harmless pill resembling the real one) alongside ubrogepant. This trial suits those who have experienced migraines for at least a year and have them on two or more days each month. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ubrogepant is generally safe for treating migraines, with studies indicating it is well-tolerated and has few side effects. Lu AG09222 has also undergone safety testing. In one study, 237 people used Lu AG09222, and researchers found it to be safe. However, since this trial is in the early stages, the safety of using Lu AG09222 and ubrogepant together is still being evaluated. While some safety information exists for each drug individually, more research is needed to understand their combined safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for migraine?

Researchers are excited about Lu AG09222 combined with ubrogepant for treating migraines because it offers a novel approach by targeting different pathways than current treatments. Most standard migraine treatments focus on either preventing or quickly stopping migraines once they start. However, Lu AG09222 is designed to work alongside ubrogepant, a CGRP receptor antagonist, potentially enhancing its efficacy. This combination might provide more comprehensive relief by not only addressing the immediate migraine symptoms but also targeting underlying mechanisms that could reduce the frequency or severity of future attacks. This dual-action strategy could represent a significant advancement in migraine management.

What evidence suggests that this trial's treatments could be effective for migraine?

Research shows that ubrogepant effectively treats migraines, reducing pain and other symptoms within two hours. In this trial, one group of participants will receive ubrogepant with Lu AG09222. Studies have found that Lu AG09222 reduces the number of migraine days by about two per month compared to a placebo. Lu AG09222 targets a protein that may cause migraines. Another group in this trial will receive ubrogepant with a placebo. Combining these treatments could offer a new way to relieve migraines. ^{3 4 6 7 8}

Who Is on the Research Team?

Email contact via H. Lundbeck A/S

Principal Investigator

H. Lundbeck A/S

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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 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 (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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05133323

NCT05133323 | A Study With Lu AG09222 in Adults ... Researchers are trying to learn whether a drug called Lu AG09222 can help prevent migraine headaches for people who have not been helped by other treatments ...

2. withpower.com withpower.com/trial/phase-1-migraine-disorders-8-2024-08d1f

Lu AG09222 + Ubrogepant for Migraine · Info for Participants 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10399003/

results from the COURAGE Study This study (COURAGE) evaluated the effectiveness of ubrogepant in combination with onabotulinumtoxinA, with an anti-CGRP monoclonal antibody ( ...

4. jmcp.org jmcp.org/doi/10.18553/jmcp.2025.31.7-a.s1

Mind over migraine: Disease burden, innovative therapies ... In a phase 2, double-blind, randomized, placebo-controlled trial, the safety and efficacy of Lu AG09222 were evaluated in a total of 237 participants (Lu ...

5. neurologylive.com neurologylive.com/view/pacap-targeted-antibody-lu-ag09222-positive-results-phase-2-migraine-trial

PACAP-Targeted Antibody Lu AG09222 Demonstrates ... Over a 4-week treatment period, patients in both Lu AG09222 groups experienced about 2 fewer migraine days per month compared with placebo.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06578585

A Trial Investigating Lu AG09222 With Ubrogepant in ... 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 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39569702/

Safety and tolerability of ubrogepant for the acute treatment ... Objective: To evaluate the safety and tolerability of ubrogepant for the acute treatment of migraine in participants taking atogepant for the ...

8. clinicaltrials.eu clinicaltrials.eu/inn/lu-ag09222/

Lu Ag09222 – Application in Therapy and Current ... Combination therapy: A study is looking at how Lu AG09222 interacts with another migraine medication called ubrogepant. Potential Side Effects and Safety.