Ensayos clínicos

PATH A (all studies NOT including the clinical trial)

Inclusion Criteria:

• Have a diagnosis of acute PTH attributed to mild traumatic injury to the head as defined by the International Classification of Headache Disorders (ICHD-3).
• PTH onset 7-28 days prior to the time of enrollment.
• Adults,18-70 years of age.
• Willing to be randomized to either of the two clinical trial treatment arms.
• Willing to maintain a headache diary.
• Willing and able to return for follow-up visits.
• Additional Inclusion Criteria for Randomization into the Clinical Trial (assessed after run-in phase).
• 5 or more moderate or severe headache days during the 4-week run-in phase.
• At least 80% compliant with diary keeping during the 4-week run-in phase (i.e., provides data on at least 80% of days).

Exclusion Criteria:

• Episodic tension-type headache, migraine, or other headaches with at least 4 headache days/month on average over the 6 months prior to the mTBI resulting in PTH.
• Previous history of chronic headache (i.e., at least 15 headache days/month) including PPTH, chronic migraine, medication overuse headache, new daily persistent headache, hemicrania continua, chronic tension-type headache.
• Diminished decision-making capacity that in the investigator’s opinion would interfere with the person’s ability to provide informed consent and complete study procedures.
• Current or prior use of preventive medications for migraine or other primary headache disorder.
• Use of onabotulinumtoxinA in the head, neck or face region within 12 months of screening.
• During the 6 months before screening, use of opioids or barbiturates on an average of at least 4 days per month.
• Subjects who underwent an intervention or used a device (e.g., nerve blocks, transcranial magnetic stimulation, vagal nerve stimulation, or electrical trigeminal nerve stimulation) for headache.
• History of major psychiatric disorder such as schizophrenia and bipolar disorder.
• History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
• History of positive neuroimaging findings that indicate a moderate or severe TBI.
• Sensory disorders that in the investigator’s opinion might affect perception of cutaneous thermal stimuli (e.g., peripheral neuropathy).
• Pregnancy.
• Breastfeeding.
• History of myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months prior to screening.
• Not willing to use a reliable form of contraception (for women of childbearing potential) through 16 weeks after the last dose of erenumab. Acceptable methods of birth control include not having intercourse, hormonal birth control methods, intrauterine devices, surgical contraceptive methods, or two barrier methods (each partner must use a barrier method) with spermicide. A reliable form of contraception must be started prior to or at the time of starting the run-in phase. Not being of childbearing potential is defined as any woman who:
  • Is post-menopausal by history, defined as:
    • At least 55 years of age with cessation of menses for 12 or more months, OR
    • Younger than 55 years of age but no spontaneous menses for at least 2 years, OR
    • Younger than 55 years of age and spontaneous menses within the past 1 year, but currently amenorrheic (e.g. spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels at least 40 IU/L) or postmenopausal estradiol level (less than 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.
• Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study.
• Has previously received any CGRP ligand or receptor targeted monoclonal antibody.

PATH B (all studies except for the clinical trial)

Inclusion Criteria:

• Have a diagnosis of acute PTH attributed to mild traumatic injury to the head as defined by the International Classification of Headache Disorders (ICHD-3).
• PTH onset 7-28 days prior to the time of enrollment.
• Adults 18-70 years of age.
• Willing to maintain a headache diary.
• Willing and able to return for follow-up visits.

Exclusion Criteria:

• Episodic tension-type headache, migraine, or other headaches with at least 4 headache days/month on average over the 6 months prior to the mTBI resulting in PTH.
• Previous history of chronic headache (i.e. at least 15 headache days/month) including PPTH, chronic migraine, medication overuse headache, new daily persistent headache, hemicrania continua, chronic tension-type headache.
• Diminished decision-making capacity that in the investigator’s opinion would interfere with the person’s ability to provide informed consent and complete study procedures.
• Current or prior use of preventive medications for migraine or other primary headache disorder.
• Use of onabotulinumtoxinA in the head, neck or face region within 12 months of screening.
• During the 6 months before screening, use of opioids or barbiturates on at least 4 days per month.
• Subjects who underwent an intervention or used a device (e.g., nerve blocks, transcranial magnetic stimulation, vagal nerve stimulation, or electrical trigeminal nerve stimulation) for headache.
• History of major psychiatric disorder such as schizophrenia and bipolar disorder.
• History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
• History of positive neuroimaging findings that indicate a moderate or severe TBI.
• Sensory disorders that in the investigator’s opinion might affect perception of cutaneous thermal stimuli (e.g., peripheral neuropathy).
• Pregnancy.
• Breastfeeding.
• Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study.

PATH C (phenotyping, molecular/genetic biomarker, clinical trial)

Inclusion Criteria:

• Have a diagnosis of acute PTH attributed to mild traumatic injury to the head as defined by the International Classification of Headache Disorders (ICHD-3).
• PTH onset 7-28 days prior to the time of enrollment.
• Adults, 18-70 years of age.
• Willing to be randomized to either of the two clinical trial treatment arms.
• Willing to maintain a headache diary.
• Willing and able to return for follow-up visits.

Exclusion Criteria:

• Episodic tension-type headache, migraine, or other headaches with at least 4 headache days/month on average over the 6 months prior to the mTBI resulting in PTH.
• Previous history of chronic headache (i.e. at least 15 headache days/month) including PPTH, chronic migraine, medication overuse headache, new daily persistent headache, hemicrania continua, chronic tension-type headache.
• Diminished decision-making capacity that in the investigator’s opinion would interfere with the person’s ability to provide informed consent and complete study procedures.
• Current or prior use of preventive medications for migraine or other primary headache disorder.
• Use of onabotulinumtoxinA in the head, neck or face region within 12 months of screening.
• During the 6 months before screening, use of opioids or barbiturates on average at least 4 days per month.
• Subjects who underwent an intervention or used a device (e.g., nerve blocks, transcranial magnetic stimulation, vagal nerve stimulation, or electrical trigeminal nerve stimulation) for headache.
• History of major psychiatric disorder such as schizophrenia and bipolar disorder.
• History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
• Pregnancy.
• Breastfeeding.
• History of myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months prior to screening.
• Not willing to use a reliable form of contraception (for women of childbearing potential) through 16 weeks after the last dose of erenumab. Acceptable methods of birth control include not having intercourse, hormonal birth control methods, intrauterine devices, surgical contraceptive methods, or two barrier methods (each partner must use a barrier method) with spermicide. A reliable form of contraception must be started prior to or at the time of starting the run-in phase. Not being of childbearing potential is defined as any woman who:
  • Is post-menopausal by history, defined as:
    • At least 55 years of age with cessation of menses for 12 or more months; OR
    • Younger than 55 years of age but no spontaneous menses for at least 2 years; OR
    • Younger than 55 years of age and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels at least 40 IU/L) or postmenopausal estradiol level (less than 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.
• Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study.
• Has previously received any CGRP ligand or receptor targeted monoclonal antibody.

PATIENT ELIGIBILITY FOR HEALTHY CONTROLS

Inclusion Criteria:

• Adults, 18-70 years of age.
• Willing and able to return for follow-up visits.

Exclusion Criteria:

• History of traumatic brain injury.
• History of migraine or other headaches:
  • Tension-type headache up to an average of 3 days per month is allowed.
• Diminished decision-making capacity that in the investigator’s opinion would interfere with the person’s ability to provide informed consent and complete study procedures
• During the 6 months before screening, use of opioids or barbiturates on an average of at least 4 days per month
• History of major psychiatric disorder such as schizophrenia and bipolar disorder
• History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
• Sensory disorders that in the investigator’s opinion might affect perception of cutaneous thermal stimuli (e.g. peripheral neuropathy).
• Pregnancy.
• Breastfeeding.
• Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study.
• Has previously received any CGRP ligand or receptor targeted monoclonal antibody.

Exclusion Criteria - PART A, PART B and HEALTHY CONTROLS

• Contraindications to magnetic resonance imaging, including, but not limited to:
  • Metal implants;
  • Aneurysm clips;
  • Severe claustrophobia;
  • Implanted electronic devices;
  • Insulin or infusion pump;
  • Cochlear/otologic/ear implant;
  • Non-removable prosthesis;
  • Implanted shunts/catheters;
  • Certain intrauterine devices;
  • Tattooed makeup;
  • Body piercings that cannot be removed;
  • Metal fragments;
  • Wire sutures or metal staples.
• Factors that reduce MR image quality and interpretability:
  • Dental braces or other non-removable devices (e.g., retainers);
  • Prior brain surgery;
  • Known brain MRI abnormality that in the investigator’s opinion will significantly impact MRI data.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 8/30/22. Questions regarding updates should be directed to the study team contact.