Ensayos clínicos

Inclusion Criteria: 

• The patient is capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• The patient is a man or woman 18 to 70 years of age, inclusive.
• The patient has a body weight ≥ 45 kg.
• Traumatic injury to the head has occurred, defined as a structural or functional injury resulting from the action of external forces. These include striking the head with or the head striking and object, penetration of the head by a foreign  body, forces generated from blasts or explosions; or whiplash has occurred, defined as sudden and inadequately restrained acceleration/deceleration movements of the head with flexion/extension of the neck. Whiplash may occur after either high or low impact forces.
• The patient has a diagnosis of PTH as per the ICHD-3 (beta version) criteria:
  • Headache is reported to have developed within 7 days after one of the following:
    • ○ mild traumatic injury to the head;
    • ○ regaining of consciousness following the injury to the head;
    • ○ discontinuation of medication(s) that impair ability to sense or report headache following the injury to the head.
• In addition, the following criteria should be met:
  • Headache persists for >1 month after injury to the head.
• During the baseline period, the patient has at least 8 headache days of at least moderate severity, defined as a day when a patient reports at least 4 hours of headache (not necessarily consecutive) and at its worst at any point has at least moderate severity; or when a patient has a headache and takes a prescription abortive medication with intent to alleviate the headache (regardless of duration or severity).
• The patient demonstrated compliance with the electronic diary during the baseline period by entry of headache data at a minimum of 75% compliance.
• The patient is not using preventive medications for headache (i.e., at least 5 half-lives have passed since last use) or is using them in a dose and regimen that have been stable for at least 2 months prior to beginning the baseline period.
• Women may be included only if they have a negative serum beta-human chorionic gonadotropin (β-HCG) test at screening and a negative urine pregnancy test at baseline, are sterile, or postmenopausal.
• Women of childbearing potential (WOCBP) whose male partners are potentially fertile (i.e., no vasectomy) must use highly effective birth control methods for the duration of the study (i.e., starting at screening) and for 30 weeks after the last IMP administration.
• Men must be sterile or, if they are potentially fertile or reproductively competent (i.e., not surgically or congenitally sterile) and their female partners are of childbearing potential, must use, together with their female partners, a condom for the duration of the study and for 30 weeks after the last IMP administration.

Exclusion Criteria: 

• The patient has a previous history of brain imaging showing evidence of intracerebral hemorrhage, subdural or epidural hematomas, or subarachnoid hemorrhage as a consequence of the traumatic head injury. Brain images with structurally insignificant changes, as discussed and approved by the sponsor, will be reviewed by the sponsor on a case-by-case basis.
• The patient has PTH attributed to craniotomy.
• The patient has whiplash and subsequent headache but no history of head injury or concussion.
• The patient has an existing headache history prior to the head trauma, unless the patient reports a significant worsening of at least 50% in the frequency and/or severity of the headaches and in the opinion of the investigator, the patient fulfills criteria for PTH.
• The patient is using analgesic medications containing opioids (including codeine) or a barbiturate on average more than 15 days per month.
• The patient has participated in another study of an IMP (or a medical device) within the previous 30 days (or 90 days for biologics) or 5.5 half-lives, whichever is longer, of the IMP or is currently participating in another study of an IMP (or a medical device) prior to screening.
• The patient has had exposure to a mAb targeting the CGRP pathway (erenumab, eptinezumab, galcanezumab, and fremanezumab) during the 6 months prior to the day of the screening visit.
• The patient is not currently being treated with onabotulinmumtoxinA (e.g., Botox, Dysport, Xeomin) application in the head or neck or has received any such injection during the 3 months prior to the screening visit.
• The patient has been implanted with any electronic devices for headache prevention during the 3 months prior to the screening visit or is currently using any implanted or externally applied stimulator or device.
• The patient has been treated with a nerve block for head and/or neck pain during the 3 months prior to the screening visit.
• The patient has a known hypersensitivity to any components of the IMPs stated in this protocol.
• The patient has a history or presence of other medical illness that, in the opinion of the investigator indicates a medical problem that would preclude study participation.
• The patient is a pregnant or lactating woman or plans to become pregnant during the study.
• The patient has clinically significant hematological, cardiac, renal, endocrine, pulmonary, gastrointestinal, genitourinary, neurologic, hepatic, or ocular disease or has any clinically significant uncontrolled medical condition (treated or untreated) at the discretion of the investigator.
• The patient has any psychiatric condition or evidence of significant active or unstable psychiatric disease that, in the opinion of the investigator, could jeopardize or would compromise the patient’s ability to participate in this study.
• The patient has major depression as assessed by the 2-item Patient Health Questionnaire (PHQ-2)/9-item Patient Health Questionnaire (PHQ-9) at screening. Any patient with a score ≥ 5 should be considered to have major depression and should be referred for appropriate treatment. Patients with lower scores (5 to 14) may also have major depression, and they should be carefully evaluated by the investigator for the presence of additional symptoms.
• The patient has a history of alcohol abuse or recreational drug abuse or at the discretion of the investigator is suspected of abusing alcohol or recreational drugs.
• The patient has any lifetime history of suicidal behaviors (suicide attempts, interrupted attempts, aborted attempts, suicidal ideation, or preparations for suicide).
• The patient fulfills any of the following criteria:
  • mentally or legally incapacitated or unable to give consent for any reason;
  • in custody due to an administrative or a legal decision, under tutelage, or being admitted to a sanitarium or social institution;
  • in current litigation for any civil or criminal offense;
  • in current, ongoing or future litigation for the life of the study, relating to headaches, trauma or injury to the brain;
  • unable to be contacted in case of emergency.
• The patient has any other condition, which, in the opinion of the investigator, makes the patient inappropriate for inclusion in the study.