Post-Traumatic HeadachePhase 2NCT03974360
Efficacy and Tolerability of Erenumab in the Prophylactic Treatment of Persistent Post-Traumatic Headache
A Phase 2 study testing AMG 334 in people with Post-Traumatic Headache and Mild Traumatic Brain Injury, run by Danish Headache Center at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Post-Traumatic Headache, Mild Traumatic Brain Injury, Post-Concussion Syndrome
- What is being tested?
- AMG 334
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- 5 Apr 2019to 31 Dec 2019
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 22Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
The reasons and justification of choosing an open-label design are the following:
- 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.
- The refractory nature of PPTH will lower the bias that could occur through placebo effects.
- 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.
- 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.
- Being tested
- AMG 334
- Medical subject headings
- Post-Traumatic Headache, Brain Concussion, Post-Concussion Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 334Drug
Also called 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)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: AMG 334 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (6)
Erenumab on number of Headache Days
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.
Measured: 12 weeks
Proportion of Patient reaching at least 75% reduction in monthly average number of headache days
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.
Measured: 12 weeks
Proportion of Patient reaching at least 50% reduction in monthly average number of headache days
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.
Measured: 12 weeks
Proportion of Patient reaching at least 25% reduction in monthly average number of headache days
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.
Measured: 12 weeks
Headache Impact Test (HIT-6)
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.
Measured: 12 weeks
Tolerability of Erenumab will be assessed by recording number and type of adverse events
To evaluate the tolerability of erenumab. Tolerability will be assessed by recording number and type of adverse events at each follow-up visit.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2019
- Study start5 Apr 2019
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post-Traumatic HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Exploratory Open-Label Study
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Danish Headache Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, Amgen
- Responsible party
- Principal investigator, Henrik Schytz, Danish Headache Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03974360
- Sponsor's protocol ID
- 2018-003943-46
- Other IDs
- 2018
- Status last verified
- Feb 2020
- First submitted
- 17 Apr 2019
- Last updated
- 10 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 32493206
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03974360
- Acronym / sponsor ID
- 2018-003943-46
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Danish Headache CenterUniversity, hospital or other
- Collaborators
- Novartis, Amgen
- Study start
- 5 Apr 2019 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 4 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The reasons and justification of choosing an open-label design are the following:
- 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.
- The refractory nature of PPTH will lower the bias that could occur through placebo effects.
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Exploratory Open-Label Study
| Arm | Type | Receives |
|---|---|---|
| Erenumab | Experimental | Drug: AMG 334100 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) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (22 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 334Also: Erenumab100 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 | Erenumab |
Primary outcome
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.
6 secondary outcomes
Erenumab on number of Headache Days
Time frame: 12 weeks
Proportion of Patient reaching at least 75% reduction in monthly average number of headache days
Time frame: 12 weeks
Proportion of Patient reaching at least 50% reduction in monthly average number of headache days
Time frame: 12 weeks
Proportion of Patient reaching at least 25% reduction in monthly average number of headache days
Time frame: 12 weeks
Headache Impact Test (HIT-6)
Time frame: 12 weeks
Tolerability of Erenumab will be assessed by recording number and type of adverse events
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2020.
- Derived from this study: PubMed 32493206Ashina 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AMG 334 in people with Post-Traumatic Headache and Mild Traumatic Brain Injury, run by Danish Headache Center at 1 site in Denmark.
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 2 inclusion and 22 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 10 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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. 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?
Effect of Erenumab on Headache Days with Moderate or Severe Intensity (time frame: 12 weeks). 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 NCT03974360, 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 10 Feb 2020; AzTrials last refreshed its copy on 8 Nov 2026.