This phase 2 study evaluated efficacy and safety of fremanezumab, (Ajovy, Teva) for the treatment of posttraumatic headache (PTH) in adult patients.

Fremanezumab, an approved preventive treatment for migraine, is a potent calcitonin-gene-related peptide (CGRP) binder that blocks both α- and β-CGRP isoforms from binding to the CGRP receptor.

After 4-week baseline, eligible patients (n=87) were randomly assigned to receive either monthly sc injections of fremanezumab (675 mg) or placebo during a 12-week double-blind period. Subsequently, 70 participants continued in a 12-week open-label period. Headache information was captured daily by participants using an electronic diary during baseline and double-blind periods. Primary efficacy endpoint was mean change from baseline in monthly average number of headache days of at least moderate severity during the 12-week period after the first dose of fremanezumab. Safety was evaluated continuously during the double-blind and open-label periods using adverse event reporting, ECGs, clinical laboratory tests and physical examination. 

For the primary efficacy endpoint, patients on fremanezumab did not observe a reduction in moderate-to-severe headache days compared to placebo (p=0.1876, -3.6 and -5.1 days for fremanezumab and placebo groups, respectively); and there were no differences in the secondary endpoints. In the double-blind period, 31 fremanezumab- and 35 placebo-treated patients reported adverse events, mostly injection site reactions. All but one AE in the placebo group were mild or moderate, and no deaths were reported. During all study periods, there were no meaningful changes in the laboratory and clinical examinations and no treatment-emergent anti-CGRP antibody response. 

This study did not demonstrate statistical differences between fremanezumab and placebo treatment for any of the efficacy endpoints. Despite being administered at a higher dose than labeled for migraine, safety data for fremanezumab 675 mg monthly was comparable to placebo administration and consistent with the known safety profile of fremanezumab.