Galcanezumab for Pediatric Migraine

(REBUILD-1 Trial)

Recruiting at 132 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: Therapeutic antibodies, CGRP antibodies

Disqualifiers: Hypersensitivity, Head injury, Intracranial tumors, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

325 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of galcanezumab, an injectable medication, in preventing migraines in children and teens. The researchers aim to determine if galcanezumab can reduce the number of migraine days each month compared to a placebo, which contains no active drug. Children aged 6 to 17 who have experienced migraines for at least six months may qualify. The study involves injections and includes an optional extension phase for continued treatment after the initial period. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking migraine prevention for young people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain therapeutic antibodies during the study.

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

Research shows that galcanezumab, a treatment for migraines, is generally safe and well-tolerated. Earlier studies with adults revealed no major safety concerns or issues with other medications. Allergic reactions occurred in a few cases, but these were rare.

The FDA has approved galcanezumab for adults with migraines, indicating it has passed strict safety tests. In those studies, over 2,500 patients used it safely. For this trial with children, it is important to note that galcanezumab has been safely used in adults, which suggests potential safety for children, although data specific to children is still being gathered. ^{1 2 3 4 5}

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

Galcanezumab is unique because it targets a specific protein called calcitonin gene-related peptide (CGRP), which plays a key role in the development of migraines. Unlike typical treatments for pediatric migraines, which often include medications like ibuprofen or triptans, galcanezumab provides a targeted approach by blocking the action of CGRP. Researchers are excited because this could mean fewer side effects and potentially better results for kids who suffer from frequent migraines. Plus, it's given as an injection, which might offer more consistent relief compared to pills that need to be taken regularly.

What evidence suggests that galcanezumab might be an effective treatment for pediatric migraine?

Research has shown that galcanezumab, which participants in this trial may receive, effectively reduces the number of migraine days. In one study, 62% of patients taking galcanezumab experienced a 50% reduction in their migraine days, compared to only 39% of those taking a placebo. Other studies indicate that it improves daily activities and lessens the emotional impact of migraines. Additionally, galcanezumab is generally well-tolerated with few side effects. Overall, it appears promising for reducing the burden of migraines. ^{1 2 6 7 8}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for kids and teens aged 6 to 17 with episodic migraines, as defined by IHS ICHD-3 guidelines. They must have had migraines for at least six months before screening. Those who've used certain therapeutic antibodies in the past year or are allergic to monoclonal antibodies can't join.

Exclusion Criteria

I haven't had a major head or neck injury in the last 6 months that worsened my headaches.

I have a history of brain tumors or specific brain malformations.

I have used or been exposed to CGRP antibodies or receptor antibodies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive either galcanezumab or placebo for the prevention of episodic migraine

3 months

Open-label Extension

All participants receive galcanezumab for further evaluation of safety and efficacy

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Galcanezumab
• Placebo

Trial Overview The study tests if Galcanezumab (LY2951742) is better than a placebo at preventing migraine headaches over three months. Participants will be randomly assigned to receive either Galcanezumab or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Galcanezumab Experimental Treatment 1 Intervention

Galcanezumab administered by SQ injection. Participants may be eligible for optional open-label extension at the end of the double-blind period.

Group II: Placebo Placebo Group 1 Intervention

Placebo administered by SQ injection. Participants may be eligible for optional open-label extension at the end of the double-blind period.

Galcanezumab is already approved in European Union, United States for the following indications:

Approved in European Union as Emgality for:

• Prophylaxis of migraine in adults who have at least four migraine days per month

Approved in United States as Emgality for:

• Preventive treatment of migraine in adults
• Treatment of episodic cluster headache

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a post hoc analysis of patients with episodic (N=879) and chronic (N=555) migraine who did not show significant improvement after 1 month of galcanezumab treatment, a notable percentage still achieved 'good' responses with continued treatment, especially those with 'modest' early improvement (62% for episodic and 38% for chronic).

Even patients with minimal or no early improvement had some chance of achieving a 'good' response with ongoing treatment, although the likelihood was lower, indicating that continued treatment may still be beneficial for certain patients despite initial lack of response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Initial Nonresponders to Galcanezumab in Patients With Episodic or Chronic Migraine: Results From the EVOLVE-1, EVOLVE-2, and REGAIN Randomized, Double-Blind, Placebo-Controlled Studies. Nichols, R., Doty, E., Sacco, S., et al.[2020]

Galcanezumab, a monoclonal antibody targeting the CGRP ligand, has shown significant efficacy in reducing the frequency of migraine attacks in both episodic and chronic migraine patients, as demonstrated in phase 3 studies involving multiple months of treatment.

Patients receiving galcanezumab reported improved quality of life and functioning, with a high percentage achieving substantial reductions in migraine days, and the treatment was well tolerated over a 12-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Galcanezumab for the Preventive Treatment of Migraine: A Narrative Review. Martin, V., Samaan, KH., Aurora, S., et al.[2021]

In a phase 3b trial involving 462 patients with chronic or episodic migraines, galcanezumab significantly reduced the number of monthly migraine headache days by an average of 4.1 days compared to 1.0 day in the placebo group, demonstrating its efficacy as a preventive treatment.

The safety profile of galcanezumab was comparable to placebo, with similar rates of treatment-emergent adverse events, indicating it is well tolerated for patients who have not responded to multiple previous migraine treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of galcanezumab in patients for whom previous migraine preventive medication from two to four categories had failed (CONQUER): a multicentre, randomised, double-blind, placebo-controlled, phase 3b trial. Mulleners, WM., Kim, BK., Láinez, MJA., et al.[2020]

Galcanezumab, a monoclonal antibody, demonstrated significant efficacy in reducing monthly migraine headache days over a 12-month period, with patients experiencing an average reduction of 8.0 to 9.0 days from a baseline of 19.4 days.

The treatment was found to be safe and well-tolerated, with a low discontinuation rate of 5% due to adverse events, indicating high adherence among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment with galcanezumab in patients with chronic migraine: results from the open-label extension of the REGAIN study. Pozo-Rosich, P., Detke, HC., Wang, S., et al.[2022]

In a Phase 2b study involving 410 patients with episodic migraine, galcanezumab was generally well-tolerated, with most treatment-emergent adverse events being mild to moderate, although some serious events were reported.

Injection-site reactions were more common with galcanezumab (13.9%) compared to placebo (5.8%), and the study supports further investigation in larger Phase 3 trials due to its safety profile and potential efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of galcanezumab in patients with episodic migraine: A randomized placebo-controlled dose-ranging Phase 2b study. Oakes, TMM., Skljarevski, V., Zhang, Q., et al.[2022]

In a 3-month study involving 462 patients with episodic or chronic migraine, galcanezumab significantly reduced interictal burden compared to placebo, as measured by the Migraine Interictal Burden Scale (MIBS-4).

The percentage of patients experiencing severe interictal burden dropped from 59% at baseline to 27% at Month 6 for those treated with galcanezumab, indicating a substantial improvement in quality of life between migraine attacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in migraine interictal burden following treatment with galcanezumab: Results from a phase III randomized, placebo-controlled study. Lipton, RB., Buse, DC., Sandoe, CH., et al.[2023]

Galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide, has shown a favorable safety and tolerability profile for up to 1 year in preventing migraines, based on data from 2276 patients across multiple studies.

Common side effects included injection site pain and reactions, but serious adverse events were low, with less than 2% of patients experiencing them, indicating that galcanezumab is a safe option for migraine prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies. Bangs, ME., Kudrow, D., Wang, S., et al.[2021]

In a study involving 1739 adult patients with episodic migraine, those treated with galcanezumab (120 mg or 240 mg) achieved a 100% response rate (no migraine headache days) significantly more often than those receiving a placebo, with rates of 13.5% and 14.3% compared to 5.9% for placebo.

The likelihood of achieving a 100% response increased over the 6-month treatment period, particularly in the last 3 months, with patients experiencing an average of 29 days between migraine headache days for those with at least 1 month of 100% response, and nearly 2 months for those with 3 or more months of 100% response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

100% Response Rate to Galcanezumab in Patients With Episodic Migraine: A Post Hoc Analysis of the Results From Phase 3, Randomized, Double-Blind, Placebo-Controlled EVOLVE-1 and EVOLVE-2 Studies. Rosen, N., Pearlman, E., Ruff, D., et al.[2019]

Galcanezumab is a humanized monoclonal antibody that targets the calcitonin gene-related peptide (CGRP), which plays a key role in migraine development, and was approved by the FDA in September 2018 for the preventive treatment of migraines in adults.

The approval was based on its efficacy in reducing the frequency of migraine days for adults experiencing at least 4 migraines per month, and it is also being studied for the prevention of cluster headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galcanezumab: First Global Approval. Lamb, YN.[2019]

Galcanezumab, a monoclonal antibody for migraine prevention, shows an early onset of action and maintains its effectiveness throughout the treatment period in both episodic and chronic migraine patients, based on data from three phase 3 studies involving 2886 participants.

After treatment cessation, galcanezumab's effects gradually diminish without causing rebound headaches, making it a safe and effective long-term preventive option for adults suffering from migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onset, Maintenance, and Cessation of Effect of Galcanezumab for Prevention of Migraine: A Narrative Review of Three Randomized Placebo-Controlled Trials. Kuruppu, DK., North, JM., Kovacik, AJ., et al.[2022]

Galcanezumab (GMB) treatment significantly reduced annual indirect costs for patients with episodic migraine (EM), leading to improved productivity at work, household tasks, and leisure activities, as shown in a study of 805 EM patients.

While GMB also provided cost savings for chronic migraine (CM) patients, these were not statistically significant, indicating that the most pronounced benefits of GMB are seen in those with episodic migraine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Annual indirect costs savings in patients with episodic or chronic migraine: a post-hoc analysis of phase 3 galcanezumab clinical trials in the United States. Varnado, OJ., Ye, W., Mi, X., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29813147/

The EVOLVE-1 Randomized Clinical Trial Galcanezumab 120-mg and 240-mg monthly injections provided clinical benefits and improved functioning. The incidence rate of adverse events was low.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03432286

NCT03432286 | A Study of Galcanezumab (LY2951742) in ... The primary objective is to demonstrate the superiority of galcanezumab versus placebo in the reduction of monthly migraine headache days across the 3-month ...

3. emgality.lilly.com emgality.lilly.com/hcp/migraine/efficacy-episodic

Episodic Migraine Efficacy | Emgality® (galcanezumab-gnlm) Mean percentage of patients who experienced a ≥50% reduction in MHDs with Emgality 120 mg was 62%c vs 39% with placebo respectively; Mean percentage of patients ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6693431/

Two randomized migraine studies of galcanezumab These results indicate that galcanezumab reduced the effect of migraine to restrict, prevent, and emotionally impair patient functioning, beginning at month 1.

5. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-023-01690-2

Long-term effectiveness and tolerability of galcanezumab in ... This study supports the effectiveness and tolerability of galcanezumab in migraine; it also provides hope for those people living with migraine ...

6. emgality.lilly.com emgality.lilly.com/hcp/migraine/conquer-study-efficacy

CONQUER Data | Emgality® (galcanezumab-gnlm) - Eli Lilly Patients taking Emgality reported improvement in the burden of migraine in between attacks, as assessed by the MIBS-4.

7. aafp.org aafp.org/pubs/afp/issues/2020/0415/p502.html

Galcanezumab (Emgality) for Migraine and Cluster ... In otherwise healthy adults, galcanezumab has not been shown to cause significant safety concerns or drug interactions. Hypersensitivity ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/761063s000lbl.pdf

EMGALITY (galcanezumab-gnlm) - accessdata.fda.gov The safety of EMGALITY has been evaluated in 2586 patients with migraine who received at least one dose of. EMGALITY, representing 1487 patient- ...