E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-traumatic headache |
Post-traumatisk hovedpine |
|
E.1.1.1 | Medical condition in easily understood language |
Headache after concussion |
Hovedpine efter et hovedtraume |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019222 |
E.1.2 | Term | Headache post-traumatic |
E.1.2 | System Organ Class | 100000004852 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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)
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 |
|
E.2.2 | Secondary objectives of the trial |
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)
To evaluate the proportion of patients reaching at least 50% reduction in the monthly average number of headache days of any severity (i.e. responders) (Time frame: baseline – week 9-12)
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 9-12)
To evaluate the mean change in disability score, as measured by the 6-item Headache Impact Test (HIT-6) from baseline – week 12
To evaluate the mean change in number of days using acute medication from baseline – week 9-12
To evaluate the tolerability of erenumab. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Men and women between 18 – 65 years who suffer from PPTH following a concussion / mild traumatic brain injury
Fertile women must use safe contraceptives or 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 |
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E.4 | Principal 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 o Underwent bilateral oophorectomy OR o Underwent hysterectomy OR o 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
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)
Change in the monthly average number of headache days from baseline to week 9-12 in PPTH patients |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
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 proportion of patients reaching at least 50% reduction in the monthly average number of headache days of any severity (i.e. responders) (Time frame: baseline – week 9-12)
The proportion of patients reaching at least 25% reduction in the monthly average number of headache days of any severity (Time frame: baseline – week 9-12)
The mean change in disability score, as measured by the 6-item Headache Impact Test (HIT-6) from baseline – week 12
The mean change in number of days using acute medication from baseline – week 9-12
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
GCP Unit region Hovedstaden |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |