Galcanezumab for Pediatric Migraine

(REBUILD-1 Trial)

Recruiting at 138 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

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: 0

325 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to evaulate the efficacy and safety of galcanezumab in participants 6 to 17 years of age for the preventive treatment of episodic migraine. The primary objective is to demonstrate the superiority of galcanezumab versus placebo in the reduction of monthly migraine headache days across the 3-month double-blind treatment period.

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.

What data supports the effectiveness of the drug Galcanezumab for treating migraines?

Research shows that Galcanezumab is effective in reducing the frequency and impact of migraines in adults, as it has been approved for preventing migraines and has shown to improve quality of life and reduce disability in patients with episodic and chronic migraines. ^{1 2 3 4 5}

Is galcanezumab safe for humans?

Galcanezumab has been studied in adults for migraine prevention and is generally considered safe, with most side effects being mild to moderate. Some serious side effects were reported, such as appendicitis and Crohn's disease, but these were rare. Common side effects included injection-site pain and upper respiratory infections. ^{1 4 6 7 8}

How is the drug Galcanezumab unique for treating pediatric migraine?

Galcanezumab is unique because it is a monoclonal antibody that targets the calcitonin gene-related peptide (CGRP), which plays a key role in migraine development. It is administered as a once-monthly subcutaneous injection, offering a preventive approach for migraines, which is different from many other treatments that are taken more frequently or only during migraine attacks. ^{1 4 9 10 11}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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 (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]

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]

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]

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]

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, 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]

References

1. United States 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. [2019]

2. United States 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. [2020]

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

Changes in migraine interictal burden following treatment with galcanezumab: Results from a phase III randomized, placebo-controlled study. [2023]

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

Galcanezumab: First Global Approval. [2019]

5. England 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. [2023]

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

Safety of galcanezumab in patients with episodic migraine: A randomized placebo-controlled dose-ranging Phase 2b study. [2022]

7. England 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. [2022]

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

Safety and tolerability of monthly galcanezumab injections in patients with migraine: integrated results from migraine clinical studies. [2021]

9. United States 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. [2022]

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

Efficacy and Safety of Galcanezumab for the Preventive Treatment of Migraine: A Narrative Review. [2021]

11. England 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. [2020]