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Cluster HeadachePhase 2CHERUB01NCT04970355

Efficacy of Erenumab in Chronic Cluster Headache

A Phase 2 study testing Erenumab in people with Cluster Headache and Trigeminal Autonomic Cephalalgias, run by Charite University, Berlin, Germany at 11 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 64 years
What is being tested?
Erenumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
101 participants
Where
11 sitesGermany
Study dates
2 Dec 2021to 27 Sep 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
  • Headache freedom from the historic diagnosis of migraine has to be at least one year prior to study inclusion. If patients have on average <=1 migraine attack per month within a year and can distinguish between migraine attacks and cluster attacks, they are allowed to participate.
  • 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)
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  • 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)
  • History or current severe coronary artery disease, myocardial infarction, stroke, transient ischemic attack, unstable angina, or coronary artery bypass surgery or other revascularization procedures within 12 months prior to screening
  • History or current diagnosis of ECG abnormalities indicating significant risk of safety for patients participating in the study- Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic protein
  • History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
  • Hepatic disease by history or total bilirubin ≥2×ULN or ALT or AST ≥3xULN as assessed by central laboratory at initial screening
  • History of severe constipation, defined as less than 3 bowel movements /week not adequately manageable by routine medical treatment, within 3 months prior to screening
  • Acute SARS-CoV2 Infection within 2 weeks prior to screening
  • Women who are pregnant or nursing
  • Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to erenumab or to any of the inactive ingredients
  • Unlikely to be able to complete all protocol required study visits or procedures, and/or to comply with all required study procedures (e.g., independent completion of electronic diary items) to the best of the patient's and investigator's knowledge
  • Prior known treatment with a CGRP receptor mAb (erenumab)
  • Prior treatment with a CGRP ligand antibody. Exceptions: Patients who participated in a randomized, placebo-controlled trial with CGRP ligand antibodies and were not unblinded (i.e., have no knowledge whether they received placebo or verum) can participate in the trial. Patients, who knowingly received a CGRP ligand antibody (i.e.galcanezumab or fremanezumab) can participate in the trial if the following criteria are met: a) Administered dose was not effective versus placebo in clinical trials i.e. galcanezumab (<300 mg/month s.c.) or fremanezumab (≤675 mg loading dose followed by 225 mg s.c./month), b) Treatment duration of maximal 2 month or 2 injection cycles c) The last dose was administered at least 6 month prior to begin of screening epoche.
  • Patients who may be dependent on the sponsor or investigator
  • Patients who are in custody of an institution due to governmental authority decision or court order

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

Germany11 sites

  • Charité Universitätsmedizin Berlin

    Berlin, 10117

  • Universitätsklinik Dresden

    Dresden, Saxony, 01307

  • Praxis für Neurologie, Nervenheilkunde, Psychosomatik

    Essen, North Rhine-Westphalia, 45133

  • Universitätsklinikum Essen

    Essen, North Rhine-Westphalia, 45147

  • Kopfschmerzzentrum Frankfurt

    Frankfurt am Main, Hesse, 65929

  • Universitätsmedizin Greifswald

    Greifswald, Mecklenburg-Vorpommern, 17475

  • Universitätsklinikum Halle

    Halle, Saxony-Anhalt, 06120

  • Vitos - Orthopädische Klinik gGmbH

    Kassel, Hesse, 34131

  • Schmerzklinik Kiel - Migräne- und Kopfschmerzzentrum

    Kiel, Schleswig-Holstein, 24149

  • LMU Klinikum München

    München, Bavaria, 81377

  • Universitätsklinikum Rostock

    Rostock, Mecklenburg-Vorpommern, 18147

Other trials in Germany

About this study

Official title: Efficacy of Erenumab in Chronic Cluster Headache: A 10 Week Double-blind, Randomized, Placebo Controlled, Multicentric Trial.

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

Read the detailed description

The purpose of this study is to determine the efficacy of erenumab in a loading dose of 280mg followed by 140mg after 4 weeks compared to placebo as a prophylactic treatment in patients with chronic cluster headache.

This study has a 10-week 2-arm, randomized, double-blind, parallel- group, placebo-controlled design. Data from this study will provide important information if the blockade of the CGRP receptor with erenumab is an efficacious principle for the treatment of chronic cluster headache

Being tested
Erenumab, Placebo
Keywords
Pain, Neurology
Medical subject headings
Cluster Headache, Trigeminal Autonomic Cephalalgias, Headache Disorders, Primary, Brain Diseases, Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ErenumabBiological

    Also called AMG 334

    Pre-filled syringe; s.c. injection

  • PlaceboDrug

    Pre-filled syring; s.c. injection

Study groups in NCT04970355
Study groupRoleWhat they receive
ErenumabExperimentalDouble-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.
Receives: Biological: Erenumab
PlaceboPlacebo comparatorDouble-Blind Treatment Phase: Participants receive placebo subcutaneous (SC) injections in week 0 and week 4.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (2)

  1. 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.

    A 50% responder is any participant who has a ≥50% reduction from baseline in the weekly number of cluster headache attacks in a 7-day interval: Weeks 5+6

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

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

    PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse.

    Measured: Baseline; Week 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2021
  2. Study start2 Dec 2021
  3. Primary completion27 Sep 2023
  4. Study completion27 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04970355
Sponsor's protocol ID
CAMG334ADE07T
Other IDs
2020-004399-16
Acronym
CHERUB01
Status last verified
Jan 2024
First submitted
11 Jul 2021
Last updated
23 Jan 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Publications

  • 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.

    PubMed 40526384

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Erenumab in people with Cluster Headache and Trigeminal Autonomic Cephalalgias, run by Charite University, Berlin, Germany at 11 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reduction of weekly cluster headache attack frequency from baseline over the last 2 weeks of the double-blind epoch (averaged for 7 days). (time frame: Baseline; Weeks 5-6 (Days 29-42)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04970355, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2024.

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