Galcanezumab for Migraine

(REBUILD-2 Trial)

Recruiting at 184 trial locations

Overseen By Seth Benjamin Forman

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of galcanezumab in preventing migraines in young people aged 12 to 17 with chronic migraines. Participants will receive either galcanezumab, a medication specifically designed to prevent migraines, or a placebo, a treatment with no active drug. The trial will compare the effectiveness in reducing migraine days each month over three months. Teens who experience headaches on 15 or more days a month, with at least 8 days showing migraine symptoms, might be suitable for this study. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new migraine prevention treatment.

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 or CGRP-related medications during the study.

Is there any evidence suggesting that galcanezumab is likely to be safe for humans?

Research shows that galcanezumab is generally well-tolerated by people with migraines. In studies, patients using galcanezumab have experienced a noticeable decrease in the number of migraine days each month. Some unwanted effects have been reported, but they are usually mild. Common side effects include reactions at the injection site and mild cold-like symptoms.

Galcanezumab has been used for both long-term and occasional migraines, and studies have found it to be safe overall. While some side effects can occur, research suggests that the treatment is generally safe. For those considering joining a trial, this information indicates that galcanezumab is generally safe to try. ^{1 2 3 4 5}

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

Galcanezumab is unique because it specifically targets and blocks the activity of a protein called calcitonin gene-related peptide (CGRP), which is involved in the development of migraine pain. Unlike traditional treatments such as triptans or NSAIDs that aim to relieve symptoms after they start, Galcanezumab works by preventing migraines from occurring in the first place. Researchers are excited because this preventative approach can reduce the frequency of migraines and improve the quality of life for those who suffer from frequent attacks. Additionally, it's administered via a simple subcutaneous injection, which is convenient for patients.

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

Research has shown that galcanezumab, which participants in this trial may receive, can reduce the number of migraine days. In studies with individuals who have chronic migraines, 28% of those taking galcanezumab experienced a 50% reduction in monthly migraine days, compared to only 15% of those taking a placebo. For those with occasional migraines, about 62% experienced a significant decrease in headache days. These findings suggest that galcanezumab can lower the number of migraine days for many individuals. ^{1 4 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

This trial is for young people aged 12 to 17 with chronic migraine, meaning they've had headaches on at least 15 days per month for the last three months, with migraine features on at least eight of those days. They can't join if they have brain tumors or malformations, are taking certain antibodies (except if used more than a year ago), have specific headache diagnoses other than chronic migraine, are allergic to monoclonal antibodies or galcanezumab's ingredients, or have used CGRP-targeting drugs recently.

Inclusion Criteria

I have chronic migraines, with headaches most days each month.

Exclusion Criteria

I have been diagnosed with a specific type of severe headache.

I have never used galcanezumab or similar medications for my condition.

I haven't taken any therapeutic antibodies in the last year, except for CGRP inhibitors which I've never taken.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either galcanezumab or placebo during the 3-month double-blind treatment period

3 months

Open-label extension

All participants receive galcanezumab during the 9-month open-label extension period

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

What Are the Treatments Tested in This Trial?

Interventions

• Galcanezumab
• Placebo

Trial Overview The study tests whether Galcanezumab is better than a placebo in reducing the number of monthly migraine days over three months in teens. Participants will be randomly assigned to receive either Galcanezumab or a placebo without knowing which one they're getting (double-blind).

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

A single intraperitoneal treatment with antibodies to glutamate significantly reduced seizure activity in C57Bl/6 mice, as observed 1.5 and 24 hours after administration.

The treatment increased the thresholds for both clonic and tonic seizures, suggesting a potential therapeutic effect in managing acute generalized epileptiform activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic administration of antibodies to glutamate increases seizure threshold for pentylenetetrazole. Evseev, VA., Karpova, MN., Vetrile, LA., et al.[2019]

In a real-world study of 52 patients in Japan, galcanezumab significantly reduced monthly migraine days by an average of 5.9 days after three doses, demonstrating its efficacy in treating migraines.

The treatment also improved associated symptoms like photophobia and nausea in over half of the patients, although more than 60% reported premonitory symptoms without subsequent headaches, indicating a need for further monitoring of these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence of galcanezumab for migraine treatment in Japan: a retrospective analysis. Takizawa, T., Ohtani, S., Watanabe, N., et al.[2023]

A 7-year-old girl with anti-LGI1 antibodies experienced refractory focal seizures that did not respond to traditional anti-seizure medications but showed rapid improvement with immunotherapy, remaining seizure-free for 2 years.

This case highlights the importance of screening for anti-LGI1 antibodies in children with severe or drug-resistant focal seizures, as isolated seizures have not been previously associated with anti-LGI1 autoimmunity in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Isolated Epileptic Seizures Associated With Anti-LGI1 Antibodies in a 7-Year-Old Girl With Literature Review. Wang, Y., Zhang, WH., Wang, Y.[2022]

Galcanezumab, a monoclonal antibody targeting the CGRP pathway, has been shown to significantly reduce migraine frequency and improve quality of life in patients, based on data from four phase-3 clinical trials.

The treatment has a favorable safety profile, with most adverse events being mild to moderate, but further research is needed to assess its long-term safety, particularly regarding cardiovascular risks and its effectiveness in treatment-resistant migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Galcanezumab in Migraine Prevention: Existing Data and Future Directions. Gklinos, P., Mitsikostas, DD.[2023]

Galcanezumab, administered monthly for up to 12 months, was found to be safe and effective in reducing the number of migraine headache days, with an average reduction of 5.6 days for the 120 mg dose and 6.5 days for the 240 mg dose among 270 patients.

The treatment showed comparable safety profiles for both doses, with only a small percentage of patients experiencing serious adverse events (3.7%) or discontinuing due to adverse events (4.8%), indicating good tolerability for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine. Camporeale, A., Kudrow, D., Sides, R., 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 study of 153 patients with autoimmune encephalitis, 89% achieved seizure freedom, with 53% doing so shortly after starting immunotherapy, highlighting the efficacy of immunotherapy in treating seizures associated with this condition.

The median time to achieve seizure freedom was significantly shorter with immunotherapy (28 days) compared to antiepileptic drugs (AEDs) (59 days), suggesting that immunotherapy should be prioritized in treatment plans for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis. de Bruijn, MAAM., van Sonderen, A., van Coevorden-Hameete, MH., 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]

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 (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 study involving 1113 patients with chronic migraine, treatment with galcanezumab significantly improved quality of life and reduced disability compared to placebo, with notable improvements in functioning as measured by the Migraine-Specific Quality-of-Life Questionnaire.

At the 3-month mark, patients receiving galcanezumab (both 120 mg and 240 mg doses) showed greater reductions in migraine-related disability compared to placebo, indicating that galcanezumab is an effective treatment option for enhancing patient functioning in chronic migraine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in patient functioning and disability: results from a phase 3, double-blind, randomized, placebo-controlled clinical trial evaluating galcanezumab for chronic migraine prevention (REGAIN). Ford, J., Tassorelli, C., Leroux, E., et al.[2021]

In a study of four patients with refractory GAD65-associated temporal lobe epilepsy, the bilateral hippocampal responsive neurostimulation (RNS) System was well tolerated and led to significant clinical improvements, with three patients experiencing over 50% seizure reduction and one becoming seizure-free after surgery.

The RNS System provided valuable long-term data on seizure patterns and helped optimize immunotherapy and antiseizure medication, suggesting it could be a promising option for managing GAD65-AE when other treatments fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain-responsive neurostimulation treatment in patients with GAD65 antibody-associated autoimmune mesial temporal lobe epilepsy. Feyissa, AM., Mirro, EA., Wabulya, A., et al.[2020]

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]

Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis is a rare autoimmune condition primarily affecting middle-aged women, characterized by symptoms like memory loss, confusion, and seizures, with MRI often showing specific brain abnormalities.

First-line treatments such as high-dose steroids and intravenous immunoglobulin are effective for most patients, and while many show a partial response to immunotherapy, second-line treatments like rituximab may be necessary for those who do not improve.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Encephalitis: A Review. Zhang, TY., Cai, MT., Zheng, Y., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6329331/

Galcanezumab in chronic migraine: The randomized ... Patients with episodic migraine treated with galcanezumab had a significantly greater mean reduction in the number of monthly migraine headache days (MHDs) and ...

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

Two randomized migraine studies of galcanezumab Patients with episodic migraine treated with galcanezumab reported significant and clinically meaningful improvements in daily functioning and decreased ...

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. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-021-01322-7

Efficacy of galcanezumab in patients with migraine and history ... This analysis confirmed the efficacy of galcanezumab 120 mg versus placebo in ≥30% reduction in monthly migraine headache days in patients with ...

5. emgality.lilly.com emgality.lilly.com/hcp/migraine/efficacy-chronic

Chronic Migraine Efficacy | Emgality® (galcanezumab-gnlm) Twenty-eightc percent of patients with chronic migraine taking Emgality 120 mg (N=273) achieved a ≥50% reduction in monthly MHDs from baseline vs 15% with ...

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. neurology.org neurology.org/doi/10.1212/WNL.0000000000203515

Efficacy and safety of different doses of subcutaneous ... Conclusions: Subcutaneous galcanezumab reduced MMDs and increased response rates in chronic and episodic migraine patients. It is generally safe except for ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02614287

NCT02614287 | A Safety Study of Galcanezumab in ... The main purpose of this study is to evaluate the longer term safety of the study drug known as galcanezumab in participants with episodic or chronic migraine.