Galcanezumab for Migraine

(REBUILD-2 Trial)

Recruiting at 183 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

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to evaluate the efficacy and safety of galcanezumab for the preventive treatment of chronic migraine in participants 12 to 17 years of age. 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 or CGRP-related medications during the study.

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

Research shows that Galcanezumab, a drug that targets a protein involved in migraines, reduces the number of migraine days and improves quality of life for people with both episodic and chronic migraines. It has been approved for preventing migraines in adults and has shown positive results in clinical trials. ^{1 2 3 4 5}

Is Galcanezumab safe for humans?

Galcanezumab has been generally found to be safe in humans, with most side effects being mild to moderate, such as injection-site pain and upper respiratory infections. Serious side effects were rare, but included conditions like appendicitis and Crohn's disease, each reported by one patient in a study. ^{1 6 7 8 9}

How is the drug Galcanezumab unique for treating migraines?

Galcanezumab is unique for treating migraines because it specifically targets and blocks a protein called calcitonin gene-related peptide (CGRP), which is involved in migraine attacks. This mechanism of action is different from traditional migraine treatments that often focus on relieving symptoms rather than preventing them. ^{10 11 12 13 14}

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 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

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

Treatment Details

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).

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

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]

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 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 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 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]

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 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]

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]

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]

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 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]

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]

References

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

Galcanezumab: First Global Approval. [2019]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

A phase 3, long-term, open-label safety study of Galcanezumab in patients with migraine. [2019]

4. 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]

5. Netherlands 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). [2021]

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

Real-world evidence of galcanezumab for migraine treatment in Japan: a retrospective analysis. [2023]

8. 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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

The Role of Galcanezumab in Migraine Prevention: Existing Data and Future Directions. [2023]

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

Evaluation of seizure treatment in anti-LGI1, anti-NMDAR, and anti-GABABR encephalitis. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Systemic administration of antibodies to glutamate increases seizure threshold for pentylenetetrazole. [2019]

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

Brain-responsive neurostimulation treatment in patients with GAD65 antibody-associated autoimmune mesial temporal lobe epilepsy. [2020]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Anti-Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptor Encephalitis: A Review. [2021]