Zavegepant Intranasal Spray for the Acute Treatment of Episodic Cluster Headache

NCT07714369 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HSC-MS-26-0153
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess headache response rate for minimal pain at 30 minutes following zavegepant administration and to assess additional effectiveness and treatment failure endpoints at various timepoints after zavegepant administration

Conditions

Cluster Headache

Keywords

Zavegepant; headache; CGRP

Outcome Measures

Primary Outcomes (1)

• Percentage of participants who achieve minimal pain at 30 minutes following their first administration of zavegepant 20mg.

  Minimal pain is defined as 0 or 1 on the 0-4 numerical rating scale.

  end of study (up to 70 days from baseline)

Secondary Outcomes (5)

• Percentage of participants who achieve minimal pain at 15 minutes following zavegepant administration

  end of study (up to 70 days from baseline)

• Percentage of participants who achieve pain freedom at 30 minutes following zavegepant administration

  end of study (up to 70 days from baseline)

• Percentage of participants who achieve pain freedom at 15 minutes following zavegepant administration

  end of study (up to 70 days from baseline)

• Percentage of participants who use rescue therapy between 30-180 minutes following zavegepant administration

  end of study (up to 70 days from baseline)

• Treatment failure as assessed by the percentage of participants with cluster headache recurrence within 3 hours

  end of study (up to 70 days from baseline)

Study Arms (1)

Zavegepant

EXPERIMENTAL

Drug: Zavegepant 20 mg

Interventions

Zavegepant 20 mg DRUG

Participants will administer zavegepant 10 mg twice in quick succession (once into the left nostril, once into the right nostril, for a total of 20mg) to treat up to 3 separate cluster headache attacks maintaining a minimum interval of 48 hours between administrations.

Zavegepant

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of episodic cluster headache according to the International Classification of Headache Disorders 3rd edition
• A history of at least 2 prior headache bouts
• Onset of cluster headache before age 50 years
• Cluster headache attacks last a minimum duration of 45 minutes (if untreated)
• Evidence of signed informed consent (ICF) as described in the protocol, indicating compliance with the requirements and restrictions listed in the ICF and this protocol

You may not qualify if:

• Pregnant or breastfeeding patients.
• Inability to follow training instructions for use of nasal device.
• Unable to speak or read English.
• Unable to access the internet (for the Questionnaires / Case Report Forms).
• Females of childbearing potential, without the ability to use 2 acceptable methods of contraception to avoid pregnancy for up to 48 hours after each study drug administration, followed by 1 acceptable method for 28 days after the last administration of study treatment.
• Body mass index ≥ 35 kg/m2
• Prisoners or subjects who are involuntarily incarcerated.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
• Have participated in another clinical research study with biological investigational agents (or other relevant agents) in the last 90 days.
• Positive drug screen for drugs of abuse at the investigator's discretion (e.g., positive amphetamines may be allowed when prescribed for an approved indication such as ADHD)
• Co-existing disease or other characteristics that precludes appropriate diagnosis of cluster headache. Other headache and facial pain disorders are allowed as long as their attacks are distinguishable from cluster headache attacks
• Currently uncontrolled, unstable, or recently diagnosed cardiovascular or neurovascular disease, Raynaud's disease, uncontrolled hypertension, a history of myocardial infarction , Acute Coronary Syndrome (ACS), Percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or Transient Ischemic Attack (TIA) in the prior 6 months
• A known history of severe hepatic impairment, or diagnosis of Gilbert's Syndrome or any other active hepatic or biliary disorder
• A history of Human Immunodeficiency Virus (HIV).
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• Pfizer: collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Cluster Headache; Headache

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Mark J Burish, MD, PhD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark J Burish, MD, PhD

CONTACT

713-486-7771; nctt.wec@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 20, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: July 20, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)