Eptinezumab for Cluster Headache

(ALLEVIATE Trial)

No longer recruiting at 167 trial locations

Overseen By Email contact via H. Lundbeck A/S

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: H. Lundbeck A/S

Must not be taking: Anti-CGRP mAbs, Gepants

Disqualifiers: Psychosis, Bipolar, Dementia, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called eptinezumab (also known as Vyepti) to evaluate its effectiveness for people with episodic cluster headaches, which are severe headaches occurring in groups or "clusters." Participants will receive either eptinezumab or a placebo (a harmless pill with no active medicine) during different periods to compare results. Suitable candidates for this trial have experienced cluster headaches for at least a year and can distinguish them from other types of headaches, such as migraines. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that eptinezumab is generally safe. Common side effects include colds and other upper respiratory infections, occurring in more than 2% of those taking eptinezumab, slightly more than in those who received a placebo.

Past research has not identified major safety issues, but limited information exists for individuals with certain heart conditions or diabetes. Therefore, while eptinezumab appears safe for most, caution is advised for those with these conditions. ^{1 2 3 4 5}

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

Eptinezumab is unique because it targets the calcitonin gene-related peptide (CGRP), a key player in causing cluster headaches. Unlike many current treatments that focus on managing symptoms or vasoconstriction, eptinezumab works by preventing headaches from occurring in the first place. Researchers are particularly excited about its potential for rapid relief, as it is administered intravenously, allowing it to circulate quickly and potentially provide faster results compared to oral medications.

What evidence suggests that eptinezumab might be an effective treatment for episodic cluster headache?

Research has shown that eptinezumab can reduce the number of migraine days. In studies, participants experienced about 50% fewer migraine days with eptinezumab compared to before treatment. It also begins working quickly to prevent migraines soon after administration. In this trial, participants will receive either eptinezumab or a placebo in different sequences. While specific data for episodic cluster headaches is limited, the success with migraines suggests potential effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Email contact via H. Lundbeck A/S

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

Inclusion Criteria

You experienced your first symptoms of cluster headache before the age of 50.

You have frequent and severe headaches called episodic cluster headaches, which have been diagnosed by a doctor and have been occurring for at least a year.

You are currently experiencing cluster headaches and have had at least one headache attack within the past week.

Exclusion Criteria

The participant has a history of clinically significant cardiovascular disease, including uncontrolled hypertension, ischaemia or thromboembolic events (for example, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism).

Participants with a lifetime history of psychosis, bipolar mania, or dementia are excluded. Participants with other psychiatric conditions whose symptoms are not controlled or who have not been adequately treated for a minimum of 6 months prior to Screening Visit 2 are also excluded.

You have chronic pain conditions like fibromyalgia or complex regional pain syndrome that may affect the study results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Placebo-controlled Period

Participants receive either eptinezumab or placebo in a blinded manner

8 weeks

2 infusions

Active Treatment Period

Participants receive the alternate treatment (eptinezumab or placebo) in a cross-over manner

8 weeks

2 infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Eptinezumab

How Is the Trial Designed?

Group I: Sequence 2: Placebo Then Eptinezumab Experimental Treatment 2 Interventions

Placebo in the Placebo-controlled Period, followed by administration of eptinezumab in the Active Treatment Period

Group II: Sequence 1: Eptinezumab Then Placebo Experimental Treatment 2 Interventions

Eptinezumab in the Placebo-controlled Period, followed by administration of placebo in the Active Treatment Period

Eptinezumab is already approved in United States for the following indications:

Approved in United States as Vyepti for:

• Preventive treatment of migraine in adults

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

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

Citations

1. vyeptihcp.com vyeptihcp.com/efficacy-and-patient-outcomes

Efficacy & Patient Outcomes | VYEPTI® (eptinezumab-jjmr) Review efficacy data from the VYEPTI pivotal trials · PRIMARY ENDPOINT · 75% FEWER MIGRAINE DAYS · FAST ONSET, SUSTAINED PREVENTION · REDUCTION IN ACUTE MED USE.

2. 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-302553630.html

Lundbeck showcases new clinical migraine data, including ... Around 50% of patients achieved a ≥50% reduction from baseline in monthly migraine days (MMDs) and achieved approximately nine days fewer MMDs ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37125484/

Efficacy and safety of eptinezumab for migraine prevention ... Results: Eptinezumab 100 and 300 mg reduced monthly migraine days more than placebo over weeks 1-12 (-4.8 and -5.3 vs -2.1, respectively; p < 0.0001). In most ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12058817/

A 24-week prospective, multicenter, real-world study on ... This real-world study documents that 24-week eptinezumab treatment is rapidly effective and well tolerated in migraine patients with multiple ...

5. vyepti.com vyepti.com/vyepti-study-results

Clinical Study Results for VYEPTI® IV Migraine Treatment People with chronic migraine who averaged 16 migraine days a month receiving VYEPTI had an average of 8 fewer migraine days a month vs 6 with placebo, over 3 ...

6. vyeptihcp.com vyeptihcp.com/safety-and-tolerability

VYEPTI Safety Profile & Tolerability Learn about VYEPTI safety results from both pivotal trials, the long-term, open-label safety and tolerability study, and common adverse reactions.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/761119s000lbl.pdf

VYEPTI (eptinezumab-jjmr) - accessdata.fda.gov The estimated rate of major birth defects (2.2%-2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women ...

8. es.aetna.com es.aetna.com/cpb/medical/data/900_999/0970.html

Eptinezumab-jjmr (Vyepti) - Medical Clinical Policy Bulletins Treatment-emergent adverse events reported by ≥2% of eptinezumab-treated patients at an incidence greater than placebo included: upper respiratory tract ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/vyepti-epar-product-information_en.pdf

Vyepti, eptinezumab - EMA Limited safety data are available in patients with cardiovascular risk factors such as diabetes, circulatory diseases and hyperlipidaemia. Patients with a ...

10. nature.com nature.com/articles/s41598-025-09490-1

Comprehensive safety analysis of adverse events ... This study aimed to thoroughly analyze the safety of eptinezumab by examining AEs using FAERS data and conducting a systematic review and meta- ...