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Efficacy and Tolerability of Erenumab in the Prophylactic Treatment of Persistent Post-Traumatic Headache

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ClinicalTrials.gov Identifier: NCT03974360
Recruitment Status : Recruiting
First Posted : June 4, 2019
Last Update Posted : June 4, 2019
Sponsor:
Collaborators:
Novartis
Amgen
Information provided by (Responsible Party):
Henrik Schytz, Danish Headache Center

Brief Summary:
An exploratory open-label study of PPTH patients to study the efficacy and tolerability of erenumab in the prophylactic treatment of persistent headache attributed to mild traumatic injury to the head. Approximately 100 subjects will be included to erenumab 140 mg. Patients who have participated in study with prior provocation (Ethics Committee of the Capital Region of Denmark (H-1801147 and H-18050498) and who have consented to be contacted will primarily be included. The study will begin February 2019 and is expected to last one year. Patients responding to advertisement (see add) will be contacted by phone.

Condition or disease Intervention/treatment Phase
Post-Traumatic Headache Mild Traumatic Brain Injury Post-Concussion Syndrome Drug: AMG 334 Phase 2

Detailed Description:

The reasons and justification of choosing an open-label design are the following:

  1. To date, there are no evidence for prophylactic drugs treating post-traumatic headache. Post-traumatic headache patients are notoriously known to be refractory to prophylactic treatment and have usually tried several prophylactic drugs such as amitriptylin, which is recommended as a prophylactic drug in migraine and chronic tension-type headache, and other drugs developed for the treatment of primary headache disorders. First step is therefore to show if there is an effect at all following erenumab treatment in these refractory PPTH patients.
  2. The refractory nature of PPTH will lower the bias that could occur through placebo effects.
  3. The treatment period is also quite long, and the endpoint is assessed in the last month of treatment, which will also minimize a placebo effect.
  4. Furthermore, this relatively small exploratory open label study is needed to show if there is an effect of erenumab in post-traumatic headache at all and what this effect is, before initiating larger multicenter double-blind studies in this patient group.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Exploratory Open-Label Study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Study to Evaluate the Efficacy and Tolerability of Erenumab in the Prophylactic Treatment of Persistent Headache Attributed to Mild Traumatic Injury to the Head
Actual Study Start Date : April 5, 2019
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Headache

Arm Intervention/treatment
Experimental: Erenumab
100 subjects with persistent post-traumatic headache will be allocated to receive monthly subcutaneous injections of 140 mg erenumab at three time points (week 0, week 4, week 8)
Drug: AMG 334
100 subjects with persistent post-traumatic headache will be allocated to receive monthly subcutaneous injections of 140 mg erenumab at three time points (week 0, week 4, week 8)
Other Name: Erenumab




Primary Outcome Measures :
  1. Effect of Erenumab on Headache Days with Moderate or Severe Intensity [ Time Frame: 12 weeks ]
    To evaluate the effect of erenumab on change in the monthly average number of headache days with moderate or severe intensity from baseline to week 9-12 in patients with persistent post-traumatic headache (PPTH). The assessment will be made using a headache diary.


Secondary Outcome Measures :
  1. Erenumab on number of Headache Days [ Time Frame: 12 weeks ]
    To evaluate the effect of erenumab on change in the monthly average number of headache days from baseline to week 9-12 in PPTH patients. The assessment will be made using a headache diary.

  2. Proportion of Patient reaching at least 75% reduction in monthly average number of headache days [ Time Frame: 12 weeks ]
    To evaluate the proportion of patients reaching at least 75% reduction in the monthly average number of headache days of any severity (Time frame: baseline - week 12). The assessment will be made using a headache diary.

  3. Proportion of Patient reaching at least 50% reduction in monthly average number of headache days [ Time Frame: 12 weeks ]
    To evaluate the proportion of patients reaching at least 50% reduction in the monthly average number of headache days of any severity (Time frame: baseline - week 12). The assessment will be made using a headache diary.

  4. Proportion of Patient reaching at least 25% reduction in monthly average number of headache days [ Time Frame: 12 weeks ]
    To evaluate the proportion of patients reaching at least 25% reduction in the monthly average number of headache days of any severity (Time frame: baseline - week 12). The assessment will be made using a headache diary.

  5. Headache Impact Test (HIT-6) [ Time Frame: 12 weeks ]

    To evaluate the mean change in disability score, as measured by the 6-item Headache Impact Test (HIT-6) from baseline - week 12.

    HIT-6 consits of six items and is a global measure of adverse headache impact to assess headache severity in the previous month and change in a patient's clinical status over a short period of time. Each of the 6 questions is responded to using 1 of 5 response categories: "never," "rarely,""sometimes," "very often," or "always." For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. Subjects will complete the HIT-6 monthly at each clinical visit.


  6. Tolerability of Erenumab will be assessed by recording number and type of adverse events [ Time Frame: 12 weeks ]
    To evaluate the tolerability of erenumab. Tolerability will be assessed by recording number and type of adverse events at each follow-up visit.


Other Outcome Measures:
  1. CGRP induced change in AUC in responders versus non-responders* [ Time Frame: 12 weeks ]
    * based on data from patients involved in the CGRP provocation (Ethics Committee of the Capital Region of Denmark (H-1801147 and H-18050498). Response is defined as patients reaching at least 50% reduction in the monthly average number of headache days of any severity from baseline to week 9-12

  2. CGRP induced incidence of exacerbations in responders versus non-responders* [ Time Frame: 12 weeks ]
    * based on data from patients involved in the CGRP provocation (Ethics Committee of the Capital Region of Denmark (H-1801147 and H-18050498). Response is defined as patients reaching at least 50% reduction in the monthly average number of headache days of any severity from baseline to week 9-12

  3. CGRP induced change in AUC* correlated to change in number of headache days from baseline - week 9-12 [ Time Frame: 12 weeks ]
    * based on data from patients involved in the CGRP provocation (Ethics Committee of the Capital Region of Denmark (H-1801147 and H-18050498). Response is defined as patients reaching at least 50% reduction in the monthly average number of headache days of any severity from baseline to week 9-12

  4. Headache phenotype* in responders versus non-responders [ Time Frame: 12 weeks ]
    *PPTH patients will be divided into patients with a migraine phenotype or a primarily tension-type headache phenotype. Headache phenotype will be assessed using a semi-structured interview.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women between 18 - 65 years who suffer from PPTH following a concussion / mild traumatic brain injury more than 12 months ago.
  • Fertile women must use safe contraceptives and present with a negative u-HCG on the experimental day. Safe contraceptives are defined as intra-uterine devices, contraceptive pills or implants and surgical sterilization.

Exclusion Criteria:

  • Pre-trauma primary headache disorders, including tension-type headache > 1 days/months
  • Medication-overuse headache
  • Whiplash injury
  • Cardiovascular disease of any kind, including cerebrovascular disease
  • Hypertension on the experimental day (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
  • Hypotension on the experimental day (systolic blood pressure < 90 mmHg and/or diastolic blood pressure < 50 mmHg)
  • Pre-trauma psychiatric disorder of any kind - unless effectively treated
  • Anamnestic or clinical symptoms of any kind that are deemed relevant for study participation by the physician who examines the patient
  • Pregnant or breastfeeding, or is a female expecting to conceive during the study,
  • including through 4 weeks after the last dose of erenumab
  • Female subject of childbearing potential who is unwilling to use an acceptable
  • Method of effective contraception during treatment through 4 weeks after the last dose of erenumab. Acceptable methods of effective birth control include not having intercourse (true abstinence, when this is in line with the preferred and usual lifestyle of the subject), hormonal birth control methods (pills, shots/injections, implants, or patches), intrauterine devices, surgical contraceptive methods (vasectomy with medical assessment of the surgical success of this procedure or bilateral tubal ligation), or two barrier methods (each partner must use one barrier method) with spermicide - males must use a condom with spermicide; females must choose either a diaphragm with spermicide, OR cervical cap with spermicide, OR contraceptive sponge with spermicide. Female subjects not of childbearing potential are defined as any female who: is post-menopausal by history, defined as:

    • Age ≥ 55 years with cessation of menses for 12 or more months, OR
    • Age < 55 years but no spontaneous menses for at least 2 years, OR
    • Age < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (eg, spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved. OR

      • Underwent bilateral oophorectomy OR
      • Underwent hysterectomy OR
      • Underwent bilateral salpingectomy
  • Known sensitivity to any component of erenumab
  • Previously randomized into an erenumab study
  • Member of investigational site staff or relative of the investigator
  • Unlikely to be able to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge

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): NCT03974360


Contacts
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Contact: Henrik Schytz, MD, PhD, DMSc 004528761824 henrik.winther.schytz.01@regionh.dk

Locations
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Denmark
Danish Headache Center Recruiting
Glostrup, Copenhagen, Denmark, 2600
Contact: Henrik Schytz, MD, PhD, DMSc    004528761824    henrik.winther.schytz.01@regionh.dk   
Sponsors and Collaborators
Danish Headache Center
Novartis
Amgen

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Responsible Party: Henrik Schytz, Associate Professor, Danish Headache Center
ClinicalTrials.gov Identifier: NCT03974360     History of Changes
Other Study ID Numbers: 2018-003943-46
First Posted: June 4, 2019    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: June 2019

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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
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Brain Concussion
Post-Concussion Syndrome
Post-Traumatic Headache
Headache
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Pain
Neurologic Manifestations
Signs and Symptoms
Head Injuries, Closed
Wounds, Nonpenetrating
Headache Disorders, Secondary
Headache Disorders
Erenumab
Antibodies, Monoclonal
Calcitonin Gene-Related Peptide Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Immunologic Factors