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

NCT03974360 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 2018-003943-46
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Post-Traumatic Headache; Mild Traumatic Brain Injury; Post-Concussion Syndrome

Outcome Measures

Primary Outcomes (1)

• Effect of Erenumab on Headache Days with Moderate or Severe Intensity

  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.

  12 weeks

Secondary Outcomes (6)

• Erenumab on number of Headache Days

  12 weeks

• Proportion of Patient reaching at least 75% reduction in monthly average number of headache days

  12 weeks

• Proportion of Patient reaching at least 50% reduction in monthly average number of headache days

  12 weeks

• Proportion of Patient reaching at least 25% reduction in monthly average number of headache days

  12 weeks

• Headache Impact Test (HIT-6)

  12 weeks

Other Outcomes (4)

• CGRP induced change in AUC in responders versus non-responders*

  12 weeks

• CGRP induced incidence of exacerbations in responders versus non-responders*

  12 weeks

• CGRP induced change in AUC* correlated to change in number of headache days from baseline - week 9-12

  12 weeks

Study Arms (1)

Erenumab

EXPERIMENTAL

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

Interventions

AMG 334 DRUG

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)

Also known as: Erenumab

Erenumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Danish Headache Center: lead
• Novartis: collaborator
• Amgen: collaborator

Study Sites (1)

Danish Headache Center

Glostrup Municipality, Copenhagen, 2600, Denmark

Location

Related Publications (1)

• Ashina H, Iljazi A, Al-Khazali HM, Eigenbrodt AK, Larsen EL, Andersen AM, Hansen KJ, Brauner KB, Morch-Jessen T, Chaudhry B, Antic S, Christensen CE, Ashina M, Amin FM, Schytz HW. Efficacy, tolerability, and safety of erenumab for the preventive treatment of persistent post-traumatic headache attributed to mild traumatic brain injury: an open-label study. J Headache Pain. 2020 Jun 3;21(1):62. doi: 10.1186/s10194-020-01136-z.

  PMID: 32493206 DERIVED

MeSH Terms

Conditions

Post-Traumatic Headache; Brain Concussion; Post-Concussion Syndrome

Interventions

erenumab

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Injuries, Traumatic; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating

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

Model Details: Exploratory Open-Label Study

Study Record Dates

• First Submitted: April 17, 2019
• First Posted: June 4, 2019
• Study Start: April 5, 2019
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: February 10, 2020

Record last verified: 2020-02

Locations

DK (1)