Lu AG09222 for Migraine

(PROCEED Trial)

Not currently recruiting at 176 trial locations

Overseen By Email contact via H. Lundbeck A/S

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lundbeck A/S

Must not be taking: Anti-PACAP

Disqualifiers: Pain syndromes, Temporomandibular disorder, Confounding headaches, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, Lu AG09222, to determine the optimal doses for preventing migraines. Participants will be divided into groups to receive different combinations of the drug or a placebo, either by injection or IV. Suitable candidates for this trial have experienced migraines for at least a year, have four or more migraine days per month, and have tried 1 to 4 other preventive medications without success. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It might be best to discuss this with the trial coordinators.

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

Research has shown that Lu AG09222 has potential in preventing migraines. One study found that a single dose of Lu AG09222 reduced migraine days more effectively than a placebo. Participants generally tolerated the treatment well.

Some side effects occurred, but they were usually mild and similar to those from other migraine treatments. This suggests that Lu AG09222 could be a safe option for people who haven't found relief with other medications. However, discussing any concerns with a doctor is always advisable. ^{1 2 3 4 5}

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

Researchers are excited about Lu AG09222 for migraine treatment because it offers a new approach that could be more effective than current options. Unlike standard treatments like triptans, which primarily target serotonin receptors, Lu AG09222 works differently by targeting other pathways involved in migraine attacks. Additionally, Lu AG09222 is administered via both subcutaneous and intravenous methods, allowing for flexible dosing options that could enhance its effectiveness and patient convenience. This novel mechanism and delivery method could provide faster relief and potentially benefit those who don't respond well to existing therapies.

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

Research has shown that Lu AG09222, which participants in this trial may receive, may help reduce migraine frequency. One study found that a single intravenous dose of 750 mg of Lu AG09222 was more effective than a placebo in reducing migraines over four weeks. This treatment blocks PACAP, a protein linked to migraines. Early results suggest that Lu AG09222 can prevent migraines, especially for those who haven't found relief with other medications. These findings offer hope for people seeking new ways to manage their migraines. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults who have suffered from migraines for over a year, get them at least 4 days each month, and haven't found relief with 2-4 other preventive medications. They must have been diagnosed according to specific guidelines and had their first migraine before turning 51.

Inclusion Criteria

I have had 4 or more migraine days each month for the last 3 months.

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

I have tried 2-4 migraine preventives in the last 10 years without success.

Exclusion Criteria

I have a history of severe headaches.

I have been diagnosed with an active jaw joint disorder.

I have been treated with anti-PACAP before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive injections of Lu AG09222 or placebo to determine the effective dose for migraine prevention

8-12 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 is testing different doses of a new medication called Lu AG09222 against a placebo to see which dose might prevent migraines in people who didn't respond well to previous treatments. Participants will be randomly assigned to receive either the drug or placebo.

How Is the Trial Designed?

Group I: Group I: Lu AG09222 IV Experimental Treatment 1 Intervention

Participants will receive Lu AG09222 by IV infusion.

Group II: Group H: Lu AG09222 IV Experimental Treatment 1 Intervention

Participants will receive Lu AG09222 by IV infusion.

Group III: Group G: Lu AG09222 IV Experimental Treatment 1 Intervention

Participants will receive Lu AG09222 by IV infusion.

Group IV: Group E: Lu AG09222 SC (closed for recruitment) Experimental Treatment 1 Intervention

Participants will receive 2 injections, each containing Lu AG09222.

Group V: Group D: Lu AG09222 SC (closed for recruitment) Experimental Treatment 2 Interventions

Participants will receive 1 injection of placebo and 1 injection containing Lu AG09222.

Group VI: Group C: Lu AG09222 SC (closed for recruitment) Experimental Treatment 2 Interventions

Participants will receive 1 injection of placebo and 1 injection containing Lu AG09222.

Group VII: Group B: Lu AG09222 SC (closed for recruitment) Experimental Treatment 2 Interventions

Participants will receive 1 injection of placebo and 1 injection containing Lu AG09222.

Group VIII: Group A: Placebo SC (closed for recruitment) Placebo Group 1 Intervention

Participants will receive 2 injections of placebo.

Group IX: Group F: Placebo IV Placebo Group 1 Intervention

Participants will receive placebo by intravenous (IV) infusion.

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

Migraine affects over 8 million people in Germany, and recent advancements in understanding its causes and new medications have greatly improved treatment options for both acute attacks and prevention.

In Germany, there are now seven approved triptans with various dosages for treating migraines, along with new preventive medications like valproic acid and topiramate, allowing doctors to customize treatment based on individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Migraine therapy]. Diener, HC., Limmroth, V.[2018]

In a trial involving 45 patients, LY293558, an AMPA/KA receptor antagonist, showed a 69% headache response rate, significantly better than placebo (25%) and comparable to sumatriptan (86%), indicating its potential efficacy in treating acute migraines.

While 15% of patients experienced adverse events with LY293558, this was lower than the 53% for sumatriptan, suggesting a favorable safety profile for LY293558 that warrants further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine. Sang, CN., Ramadan, NM., Wallihan, RG., et al.[2012]

LY466195 is a highly potent selective antagonist of the GLU(K5) kainate receptor, showing strong efficacy in reducing migraine-related responses in animal models, with effective doses as low as 1 microg/kg.

The compound demonstrated safety in vitro, showing no contractile activity in rabbit veins and no significant behavioral side effects at high oral doses, suggesting a favorable safety profile for potential therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological characterization of the competitive GLUK5 receptor antagonist decahydroisoquinoline LY466195 in vitro and in vivo. Weiss, B., Alt, A., Ogden, AM., et al.[2014]

In a study involving two Phase 3 trials with patients experiencing migraines, a second dose of lasmiditan showed some effectiveness for treating headache recurrence, with 50% of patients pain-free compared to 32% with placebo.

However, there was no significant benefit of a second dose for rescue treatment, and the safety profile was similar for lasmiditan and placebo, indicating that the second dose did not increase the risk of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: findings from the phase 3 trials (SAMURAI and SPARTAN). Loo, LS., Plato, BM., Turner, IM., et al.[2020]

Sumatriptan, a 5-HT(1B/1D/1F) receptor agonist, has significantly advanced the acute treatment of migraines, leading to the development of new triptans and other pharmacological options.

The review highlights the importance of experimental models in understanding migraine mechanisms and improving treatment strategies, suggesting that these models will enhance future migraine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological aspects of experimental headache models in relation to acute antimigraine therapy. De Vries, P., Villalón, CM., Saxena, PR.[2019]

Citations

1. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2314577

A Monoclonal Antibody to PACAP for Migraine Prevention In a phase 2 trial, a single intravenous infusion of 750 mg of Lu AG09222 showed superiority over placebo in reducing migraine frequency over the subsequent 4 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39231342/

A Monoclonal Antibody to PACAP for Migraine Prevention In a phase 2 trial, a single intravenous infusion of 750 mg of Lu AG09222 showed superiority over placebo in reducing migraine frequency over the subsequent 4 ...

3. prnewswire.com prnewswire.com/news-releases/lundbeck-showcases-new-clinical-migraine-data-including-long-term-preventive-effectiveness-of-vyepti-eptinezumab-in-patients-severely-impacted-by-migraine-302553629.html

Lundbeck showcases new clinical migraine data, including ... ... Lu AG09222 (anti-PACAP mAb); New data from the open-label extension of the RESOLUTION trial and the primary results of the SUNSET extension ...

4. 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 ...

5. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-023-01599-w

The effect of Lu AG09222 on PACAP38- and VIP-induced ... This proof-of-mechanism study demonstrated that Lu AG09222 inhibited PACAP38-induced cephalic vasodilation and increases in heart rate, and reduced concomitant ...

6. jwatch.org jwatch.org/na57935/2024/10/21/efficacy-and-safety-novel-monoclonal-antibody-migraine

Efficacy and Safety of a Novel Monoclonal Antibody for ... Participants in the Lu AG09222 750-mg group showed significantly greater improvement through week 4 than the placebo group (−6.2 vs. −4.2 days).