Efficacy of Erenumab in Chronic Cluster Headache

NCT04970355 | Completed Phase 2 FDA Drug

• 2 other identifiers: CAMG334ADE07T2020-004399-16
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 11

Brief Summary

The main purpose of this study is to evaluate the efficacy of erenumab in participants with chronic cluster headache.

Conditions

Cluster Headache; Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Brain Disease

Keywords

Pain; Neurology

Outcome Measures

Primary Outcomes (1)

• Reduction of weekly cluster headache attack frequency from baseline over the last 2 weeks of the double-blind epoch (averaged for 7 days).

  Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary, Baseline and 6 weeks of daily data during double-blind treatment phase will be converted into 7-calendar day intervals: The baseline 7-10 day interval, Week 5+6.

  Baseline; Weeks 5-6 (Days 29-42)

Secondary Outcomes (2)

• Percentage of participants with a 50% or greater reduction from baseline in the weekly number of cluster headache attacks averaged per 7 days over the last 2 weeks of the DB epoch.

  Baseline; Weeks 5-6 (Days 29-42)

• Patient Global Impression of Improvement (PGI-I) at week 6.

  Baseline; Week 6

Other Outcomes (12)

• Reduction from baseline in the weekly number of CH attacks in each of the last 2 weeks of the double blind epoch.

  Baseline, Week 5; Week 6

• Reduction from baseline in the number of weekly CH attacks over the entire double-blind trial period (day 1-42).

  Baseline, Weeks 1- 6

• Safety and tolerability of erenumab/placebo

  Baseline; Week 1-Week 10

Study Arms (2)

Erenumab

EXPERIMENTAL

Double-Blind Treatment Phase: Participants receive erenumab 280 mg subcutaneous (SC) injections (loading dose, week 0) followed by erenumab 140 mg s.c. in week 4.

Biological: Erenumab

Placebo

PLACEBO COMPARATOR

Double-Blind Treatment Phase: Participants receive placebo subcutaneous (SC) injections in week 0 and week 4.

Drug: Placebo

Interventions

Erenumab BIOLOGICAL

Pre-filled syringe; s.c. injection

Also known as: AMG 334

Erenumab

Placebo DRUG

Pre-filled syring; s.c. injection

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults ≥18 and \< 65 years of age
• Documented history of chronic cluster headache for ≥12 months prior to screening according to the International Classification of Headache Disorders-3rd Edition (ICHD-3)
• Participants are able to distinguish cluster headache attacks from other headaches.
• Insufficient efficacy OR tolerability OR contraindications of approved cluster headache prophylactic medications. Insufficient efficacy and tolerability as determined by the patient.
• Sufficient acute attack treatment with triptans or oxygen based on the patient´s history
• The patient is able to distinguish cluster headache attacks from other headaches (i.e. tension-type headaches).
• At least 9 cluster headache attacks as defined by the ICHD-3 in 7 days during the baseline epoch (SPII), confirmed by patient-reported eDiary entries.
• Attacks must have occurred on more than 50% of days of the baseline epoch (SPII).
• ≥ 90% patient-reported eDiary compliance during the Baseline epoch, compliance is measured as interacting with e-Diary at least once a day.

You may not qualify if:

• Diagnosis or history of other primary headache diseases according to the International Classification of Headache Disorders, 3rd Edition (ICHD-3), excluding episodic tension type headache and migraine as defined in criterion 2.
• Unable to differentiate cluster headache attacks from other headaches
• Use of a prophylactic cluster headache medication within 5 half-lives prior to the start of the baseline phase
• Parallel use of an SPG stimulator, deep brain stimulation or parallel use of a device for the acute/preventive treatment of chronic cluster headache
• Administration of botulinum toxin type A or B in the head or neck area, within 4 months of baseline (SP II)
• Concurrent use of other therapeutic monoclonal antibodies.
• Current use or any prior exposure to any calcitonin-gene-related peptide (CGRP) antibody, any antibody to the CGRP receptor
• Use of other investigational drugs within 5 half-lives of enrollment, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer
• Evidence of drug, opioid or alcohol abuse or dependence within 12 months prior to screening, based on medical records or patient self-report
• History of use of psilocybin (mushrooms), LSD, MDMA or 2- bromo-LSD within 2 months prior to baseline (SPII)
• Have a positive urine drug screen (UDS) for any substances of abuse, except cannabis or cannabinoids, prior to randomization. A retest is applicable if, in judgment of the investigator, there is a reasonable explanation for the positive result. A negative result in the retest is obligatory for entering baseline (SPII)
• Diagnosis or history of significant active or unstable psychiatric disease, such as bipolar disorder, schizophrenia, personality disorders, or other serious mood or anxiety disorders. Patients with anxiety disorder and/or major depressive disorder are permitted in the study if they are considered by the investigator to be stable and are taking no more than one medication per disorder. Patients must have been on a stable dose within the 3 months prior to the start of the baseline phase
• Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the Columbia Suicide Severity Rating Scale (C-SSRS), if this ideation occurred in the past month, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 3 months. Patients who do not meet this criterion, but who are considered by the judgment of the investigator to be at significant risk for suicide, must be excluded
• Active chronic pain syndromes (e.g., fibromyalgia or chronic pelvic pain) in which the pain has lost its guiding and warning function and has acquired an independent disease value.
• History or current evidence of major psychiatric disorder (such as schizophrenia, bipolar disorder or type B personality disorder that might interfere with the ability to properly report clinical outcomes)

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (11)

LMU Klinikum München

München, Bavaria, 81377, Germany

Location

Kopfschmerzzentrum Frankfurt

Frankfurt am Main, Hesse, 65929, Germany

Location

Vitos - Orthopädische Klinik gGmbH

Kassel, Hesse, 34131, Germany

Location

Universitätsmedizin Greifswald

Greifswald, Mecklenburg-Vorpommern, 17475, Germany

Location

Universitätsklinikum Rostock

Rostock, Mecklenburg-Vorpommern, 18147, Germany

Location

Praxis für Neurologie, Nervenheilkunde, Psychosomatik

Essen, North Rhine-Westphalia, 45133, Germany

Location

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Universitätsklinik Dresden

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Halle

Halle, Saxony-Anhalt, 06120, Germany

Location

Schmerzklinik Kiel - Migräne- und Kopfschmerzzentrum

Kiel, Schleswig-Holstein, 24149, Germany

Location

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Related Publications (1)

• Mecklenburg J, Gaul C, Fitzek M, Overeem LH, Heinze A, Fleischmann R, Boeger A, Holle-Lee D, Straube A, Gendolla A, Israel-Willner H, Lorenz M, Gossrau G, Naegel S, Rimmele F, Rattan S, Materne B, Schulze D, Raffaelli B, Reuter U; CHERUB01 Study Group. Erenumab for Chronic Cluster Headache: A Randomized Clinical Trial. JAMA Netw Open. 2025 Jun 2;8(6):e2516318. doi: 10.1001/jamanetworkopen.2025.16318.

  PMID: 40526384 DERIVED

MeSH Terms

Conditions

Cluster Headache; Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Brain Diseases; Pain

Interventions

erenumab

Condition Hierarchy (Ancestors)

Headache Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Uwe Reuter, MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurologist

Study Record Dates

• First Submitted: July 11, 2021
• First Posted: July 21, 2021
• Study Start: December 2, 2021
• Primary Completion: September 27, 2023
• Study Completion: September 27, 2023
• Last Updated: January 23, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Data are available 6 months after the primary publication.
• Access Criteria: A research proposal must be approved by Charité Universitätsmedizin Berlin. Researchers must sign a data sharing agreement.

Locations

DE (11)