Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of Erenumab in Chronic Cluster Headache (CHERUB01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04970355
Recruitment Status : Recruiting
First Posted : July 21, 2021
Last Update Posted : December 2, 2021
Sponsor:
Information provided by (Responsible Party):
Prof. Uwe Reuter, Charite University, Berlin, Germany

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

Condition or disease Intervention/treatment Phase
Cluster Headache Trigeminal Autonomic Cephalalgias Headache Disorders, Primary Brain Disease Biological: Erenumab Drug: Placebo Phase 2

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Efficacy of Erenumab in Chronic Cluster Headache: A 10 Week Double-blind, Randomized, Placebo Controlled, Multicentric Trial.
Actual Study Start Date : October 28, 2021
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : July 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Headache
Drug Information available for: Erenumab

Arm Intervention/treatment
Experimental: Erenumab
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
Pre-filled syringe; s.c. injection
Other Name: AMG 334

Placebo Comparator: Placebo
Double-Blind Treatment Phase: Participants receive placebo subcutaneous (SC) injections in week 0 and week 4.
Drug: Placebo
Pre-filled syring; s.c. injection




Primary Outcome Measures :
  1. 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) ]
    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.


Secondary Outcome Measures :
  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. [ Time Frame: Baseline; Weeks 5-6 (Days 29-42) ]
    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

  2. Patient Global Impression of Improvement (PGI-I) at week 6. [ Time Frame: Baseline; 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.


Other Outcome Measures:
  1. Reduction from baseline in the weekly number of CH attacks in each of the last 2 weeks of the double blind epoch. [ Time Frame: Baseline, Week 5; Week 6 ]
    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 and week 6.

  2. Reduction from baseline in the number of weekly CH attacks over the entire double-blind trial period (day 1-42). [ Time Frame: Baseline, Weeks 1- 6 ]
    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 1-week 6

  3. Safety and tolerability of erenumab/placebo [ Time Frame: Baseline; Week 1-Week 10 ]
    Number of AEs, TEAEs, SAEs, and number of patients discontinue study participation stratified for treatment and non-treatment related discontinuation.

  4. Discontinuation of the study due to intolerable attack frequency or severity during the double-blind epoch of the study. [ Time Frame: Baseline; Week 1-Week 6 ]
    To compare erenumab with placebo in reduction of frequency and intensity of CH attacks assessed by the rate of patients discontinuing the study due to intolerable attack frequency or severity.

  5. Number of patients achieving at least a 30% reduction from baseline in weekly CH attacks averaged over the last 2 weeks (days 29-42) of the double-blind epoch [ Time Frame: Baseline, Week 5-Week 6 ]
    A 30% responder is any participant who has a ≥30% reduction from baseline in the weekly number of cluster headache attacks in a 7-day interva in Weeks 5+6

  6. Number of patients achieving at least a 70 % reduction from baseline in weekly CH attacks averaged over the last 2 weeks (days 29-42) of the double-blind epoch. [ Time Frame: Baseline, Week 5-Week 6 ]
    A 70% responder is any participant who has a ≥70% reduction from baseline in the weekly number of cluster headache attacks in a 7-day interval: Weeks 5+6

  7. Change from baseline in SF-12 quality of life at week 6 (day 42). Difference between erenumab and placebo scores at week 6 [ Time Frame: Baseline; Week 6 ]
    This information will help keep track of how participants feel and how well they are able to do usual activities.

  8. Change from baseline in HIT-6 quality of life at week 6 (day 42). Difference between erenumab and placebo scores at week 6 and improvement of HIT-6 scores from baseline. [ Time Frame: Baseline; Week 6 ]
    This information will allow to assess the impact of attacks on headache related disability. The recall period for 3 questions is 4weeks & the remaining questions do not have a specific recall period.

  9. Change from baseline in average duration in minutes of recorded CH attacks over the last 2 weeks (days 29-42) of the double-blind epoch. [ Time Frame: Baseline: Weeks 5-6 ]
    Duration of CH 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.

  10. Change from baseline in frequency of acute medication per week averaged over week 5 and 6 (days 29-42). [ Time Frame: Baseline: Weeks 5-6 ]
    Baseline data and the mean change from baseline in the overall weekly average number of days with the use of cluster-specific acute headache medications (as liosted in the protocoll) during weeks 5-6 after administration of the first dose of study drug (based on Week 0 to 5-6 data) is reported.

  11. Change from baseline in average intensity in average numerical pain rating scale value of recorded attacks over week 5 and 6 (days 29-42). [ Time Frame: Baseline: Weeks 5-6 ]
    Participants marked the level of CH-associated pain using the numerical pain ratiung scale.

  12. Discontinuation of treatment due to all-cause during the double-blind epoch of the study [ Time Frame: Weeks 1-8 ]
    Rate of patients discontinuing treatment due to any cause during the double-blind treatment period.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (screening)

  • 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).

Inclusion Criteria (Baseline)

  • 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.

Exclusion Criteria:

  • 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.
  • 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 cannabis, cannabinoids, 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 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)
  • 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 treatment with a CGRP receptor mAb or a CGRP mAb
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04970355


Contacts
Layout table for location contacts
Contact: Mario Lorenz +49 30 450 660139 ma.lorenz@charite.de
Contact: Jasper Mecklenburg, MD +49 30 450 660107 jasper.mecklenburg@charite.de

Locations
Layout table for location information
Germany
LMU Klinikum München Not yet recruiting
München, Bayern, Germany, 81377
Contact: Andreas Straube, MD         
Kopfschmerzzentrum Frankfurt Not yet recruiting
Frankfurt, Hessen, Germany, 65929
Contact: Charly Gaul, MD         
Universitätsklinikum Rostock Not yet recruiting
Rostock, Mecklenburg-Vorpommern, Germany, 18147
Contact: Florian Rimmele, MD         
Praxis für Neurologie, Nervenheilkunde, Psychosomatik Not yet recruiting
Essen, Nordrhein Westfalen, Germany, 45133
Contact: Astrid Gendolla, MD         
Universitätsklinikum Halle Recruiting
Halle, Sachsen-Anhalt, Germany, 06120
Contact: Steffen Nägel, MD         
Schmerzklinik Kiel - Migräne- und Kopfschmerzzentrum Not yet recruiting
Kiel, Schleswig-Holstein, Germany, 24149
Contact: Hartmut Göbel, MD         
Charité Universitätsmedizin Berlin Recruiting
Berlin, Germany, 10117
Contact: Uwe Reuter, MD    +4930450560 ext 274    uwe.reuter@charite.de   
Contact: Jasper Mecklenburg, MD    +4930450660 ext 107    jasper.mecklenburg@charite.de   
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
Layout table for investigator information
Principal Investigator: Uwe Reuter, MD Charite University, Berlin, Germany
Layout table for additonal information
Responsible Party: Prof. Uwe Reuter, Neurologist, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT04970355    
Other Study ID Numbers: CAMG334ADE07T
2020-004399-16 ( EudraCT Number )
First Posted: July 21, 2021    Key Record Dates
Last Update Posted: December 2, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
Supporting Materials: Clinical Study Report (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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Prof. Uwe Reuter, Charite University, Berlin, Germany:
Pain
Neurology
Additional relevant MeSH terms:
Layout table for MeSH terms
Brain Diseases
Cluster Headache
Headache Disorders
Headache Disorders, Primary
Trigeminal Autonomic Cephalalgias
Headache
Pain
Neurologic Manifestations
Central Nervous System Diseases
Nervous System Diseases
Erenumab
Calcitonin Gene-Related Peptide Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs