A single arm, open label, multicenter study of the safety and efficacy of Nerivio for the acute treatment of migraine in adolescents (NCT04089761)

A clinical study of the Nerivio device in adolescents with migraine (ages 12-17 years old) was performed to assess the safety and clinical efficacy of Nerivio in adolescents with migraine.

The study was a prospective, open-label, single arm, multicenter study conducted at 12 sites in the USA. Eligible participants were adolescents (12–17 years old, inclusive) who met the International Classification of Headache Disorders (ICHD-3) criteria for migraine. all the inclusion criteria and none of the exclusion criteria.

Following a 4 week “run-in” phase, eligible participants were asked to treat 4 qualifying migraine attacks at home with their optimal stimulation intensity, as soon as possible after migraine headache began and always within one hour of attack onset. Participants were instructed to avoid taking rescue medications prior or within the first two hours post-treatment. Pain scores, absence/presence of migraine associated symptoms, and functional disability were recorded at baseline, 2- and 24-hours post-treatment using the electronic diary application. Improvement in migraine-related disability following the treatment phase was assessed using the Pediatric Migraine Disability Assessment (PedMIDAS) questionnaire.

Efficacy and safety outcome

The primary safety endpoint was assessed by the incidence of adverse events in general and by seriousness, severity and association to the device. Treatment tolerability was assessed by the percent of subjects who fail to complete the study because of adverse events.

The secondary endpoints were related to device efficacy and included the proportion of participants who achieved pain relief at 2 hours post-treatment, defined as improvement from severe or moderate pain to mild or none, or improvement from mild pain to none; proportion of participants who achieved pain-free (improvement from mild, moderate, or severe pain to none) at 2 hours, and disappearance of associated symptoms (nausea/vomiting, photophobia, and phonophobia) at 2 hours post-treatment.

Exploratory endpoints included sustained pain relief at 24 hours, sustained pain-free at 24 hours, and improvement in functional ability at 2 hours and at 24 hours. Within-subject consistency of pain relief and pain-free responses, defined as the proportion of participants achieving pain relief/pain-free at 2 hours post-treatment in at least 50% of their treated headaches, were also assessed.

Disposition of patients

60 patients were enrolled, of which 1 participant was lost to follow-up during the run-in phase, and 14 completed the run-in but were not eligible to continue according to protocol specifications. Among the 45 participants who entered the treatment phase, all participants completed at least one treatment (the training treatment) and 39 participants completed the test treatment, forming the final analysis set (two participants had missing data at 2 hours post-treatment, three participants did not have migraine headaches and one participant was a lost to follow-up).

A total of 159 qualifying migraine headaches were treated with Nerivio for which pain data was recorded at baseline and at 2 hours post-treatment (average of 3.5 treatments per participant). Pain levels at baseline were 15.7% mild (25/159), 48.4% moderate (77/159) and 35.8% severe (57/159). Participant disposition is presented in figure 1

Figure 1 – Participant disposition

Results

The participants demographic information is shown in table 1.

Characteristic Age, y (SD)15.4 (1.8)Female, % (n/N)60.0% (36/60)Race, % (n/N)Caucasian (including Hispanic)86.6% (52/60)African/ Eastern Arab1.66% (1/60)African American10.0% (6/60)American Indian or Alaskan Native1.66% (1/60)Average number of headache days per month9.6 (4.6)Average number of migraine headache days per month7.9 (3.9)Triptan users, % (n/N)30.0% (18/60)Migraine with aura, % (n/N)31.7% (19/60)MBS % (n/N)*Nausea35.0% (21/60)Photophobia43.3% (26/60)Phonophobia16.7% (10/60)None5.0% (3/60)

Table 1 – Participants demographic information

Run-in phase

A total of 267 qualifying migraine attacks were reported during the run-in phase by 54 of the 60 enrolled patients (6 patients did not report any migraines during the run-in phase), with an average of 4.9 migraine attacks per participant.

Treatment phase

Safety analysis

Safety analyses were performed on all 45 participants who used the device at least once. 10 participants (22.2%) reported at least one adverse event. There was one device-related adverse event reported (2.2%) in which a temporary feeling of pain in the arm was felt. This adverse event was mild and resolved after the treatment without requiring medication or any other intervention. The other adverse events were deemed unrelated to the device included common cold (1 participant), chest congestion (2 participants), influenza (2 patients), leg pain (1 patient), streptococcus pharyngitis (1 participant), upper respiratory infection (1 patient), and worsened migraine (1 patient). There were no device-related serious adverse events and none of the participants withdrew from the study due to device-related adverse events.

Efficacy analysis

The efficacy endpoints were conducted on the test treatment of the final analysis set of 39 participants. Pain relief and pain-free at 2 hours were achieved by 71.8% (28/39) and 35.9% (14/39) participants, respectively. For the primary efficacy endpoint, missing data was imputed using a worst-case scenario, in which all treatments with missing pain level data were considered failures. According to this sensitivity analysis, pain relief was achieved by 68.3% (28/41) of the participants.

Pain relief was sustained for 24 hours in 90.9% (20/22) of the participants, and pain freedom was sustained for 24 hours in 90.9% (10/11) of the participants (only subjects achieving relief/freedom at 2 hours were included in the analyses; 6 participants did not report pain level at 24 hours and were thus excluded from the analysis). Nausea, photophobia, and phonophobia disappeared at 2 hours in 54.5% (12/22), 41.9% (13/31), and 40.0% (10/25) participants, respectively. Furthermore, 69.7% (23/33) participants experienced improvement in functional ability at 2 hours (only participants with functional disability at baseline were included in the analysis) and 69.0% (20/29) participants experienced improvement in functional ability at 24 hours (only participants with functional disability at baseline were included in the analysis; 4 participants with missing data at 24 hours were excluded from the analysis). In order to assess long-term response to the treatment, a consistency analysis was conducted across all treated attacks (excluding the training treatment). This analysis demonstrated that 66.7% (26/39) of the participants experienced pain relief in at least 50% of their treated attacks, and 33.3% (13/39) of the participants experienced pain-free in at least 50% of their treated attacks.

Headache disability as determined by the impact of recurrent headaches on a patient’s quality of life was assessed using the Pediatric Migraine Disability Assessment (PedMIDAS) questionnaire. 42 participants who completed the questionnaire both at baseline and at the end of treatment phase were included in the analysis. The change between the PedMIDASs at enrollment (37.1±30.4) and the end of the treatment phase (18.5±26.8) was 18.6 ± 23.4. These results indicate that treating migraine headaches with Nerivio significantly decreases migraine disability. Interestingly, the average decrease observed in the current study is similar to the reduction shown for migraine preventive treatments in the pediatric population. These findings suggest that Nerivio is effective for improving patients’ quality of life.

Endpoint

Result

Pain-free at 2 hours post-treatment(in the test treatment)71.8% (28/39)Disappearance of associated symptoms at 2 hours post-treatment35.9% (14/39)Disappearance of nausea54.5% (12/22)Disappearance of photophobia41.9% (13/31)Disappearance of phonophobia40.0% (10/25)Sustained pain relief at 24 hours post-treatment (in the test treatment)90.9% (20/22)Sustained pain free at 24 hours post-treatment (in the test treatment)90.9% (10/11)Improvement in functional ability at 2 hours69.7% (23/33)Improvement in functional ability at 24 hours69.0% (20/29)

Table 2 – Efficacy outcome

The perceived usability of Nerivio was assessed using the system usability scale (SUS). 42

participants who completed the questionnaire at the end of treatment phase were included in the analysis. The mean SUS score was 85.1±12.7. These results indicate high levels of acceptability, ease of use, learnability and confidence when using Nerivio.

The results of the study show that Nerivio is safe and effective for the acute treatment of migraine in adolescents.

Conclusions:

Performance data demonstrate that the Nerivio is safe and effective for acute treatment of migraine in adolescents as it is in adult patients, resulted in clinically meaningful benefits (pain relief and pain freedom)

The results of the study show that Nerivio is safe and effective for the acute treatment of migraine in adolescents. There was one device-related adverse event in which a temporary feeling of pain in the arm was felt. This adverse event was mild and resolved after the treatment without requiring medication or any other intervention. This rate of device-related adverse events compares favorably to the reported rates for current pharmacological treatments.

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