Prospective post marketing study of acute treatment of migraine assessing the safety and efficacy of Nerivio in children under the age of 12 (NCT06138756)

Background

Migraine has a substantial impact on the lives of young children. Affecting up to 10% of children under 12 years old. Migraine attacks significantly disrupt childhood, hindering schooling, social activities, and sleep, leading to a significant reduction in quality of life. However, the landscape for the acute treatment of migraine in children aged 6-12 is extremely limited. The lack of efficient treatments for the treatment of migraine in children has led to a significant unmet need for efficacious and well‐tolerated migraine treatments.

Based on the above considerations, Theranica performed a post-market data analysis of prospectively collected Real World Data to evaluate the safety and efficacy of the Nerivio device in children ages 6 to 11 years-old, and compared the results found in this target population to the results that were found in adolescents and adults.

Study primary endpoint

Device safety

The incidence of adverse events in general and by seriousness, severity and association to the device, as reported by the users, or by inquiries made by the subjects and/or their parents to Theranica USA customer support service All adverse events that were reported by participants were analyzed including the following information: device-related AEs, description, severity and whether they were serious. and all other Nerivio patients.

Secondary efficacy endpoints

Efficacy.

Consistent Headache Relief at 2 Hours Post-treatment: The proportion of subjects reporting headache relief at 2 hours post-treatment in at least 50% of all their treatments.

Consistent Freedom From Headache at 2 Hours Post-treatment: The proportion of subjects reporting freedom from headache at 2 hours post-treatment in at least 50% of all their treatments.

Consistent Functional Disability Relief at 2 Hours Post-treatment: The proportion of subjects who reported having Functional Disability at the beginning of the treatment and reported improvement of at least one level of Functional Disability at 2 hours post-treatment in at least 50% of all their treatments.

Consistent Functional Disability disappearance at 2 Hours Post-treatment: The proportion of subjects who reported having Functional Disability at the beginning of the treatment and reported no Functional Disability at 2 hours post-treatment in at least 50% of all their treatments.

Freedom from a specific migraine associated symptoms : Freedom from a specific migraine associated symptom was calculated as the percent of patients reporting the presence of that symptom at T=0h, and the lack of that symptom at T=2h post-treatment.

Results

Two hundred and ninety-three (n=293) children 6-11 years old (73.7% female) used the Nerivio device from May 2020 to December 2023 to treat at least one migraine attack and were therefore included in the study (the ITT population). Patient age ranged between 6 to 11 years, inclusive, with gradually more patients in the older age groups (median=11, IQR=9-11; see Table 1). Of them, 18.4% reported at least one attack with aura (girls – 41/216=18.9%, boys – 13/77=16.8%). The remaining 81.6% never reported aura.

Categorical VariablesCount (%)Total NGirlsBoysEnrolled (ITT population)293 (100)216 (73.7)77 (26.3)Age group (years)11151 (51.5)114 (52.8)37 (48.1)1068 (23.2)52 (24.1)16 (20.8)934 (11.6)21 (9.7)13 (16.9)826 (8.9)17 (7.9)9 (11.7)6-714 (4.8)12 (5.6)2 (2.6)Aura in at least 1 attack54 (18.4)41 (18.9)13 (16.8)Continuous VariablesMeanSDMedianMinMaxAge (N=293)10.11.211611Treatments per patient during study period (N=293)

18.7

36.1

10

1

499

Table 1 – Patient demographics and baseline clinical characteristics (ITT)

293 participants were identified according to the study inclusion criteria. Pre- and post-treatment headache and disability reports (at T=0 and T=2h) for the same treatment session were available for at least two treatment sessions for 62 and 50 subjects, respectively. Of these reports, 33 and 24 patients had multiple reports for headache and disability without medication intake that allows the analysis of the Nerivio effect as a stand-alone treatment. Following removal of the first treatment in order to reduce the learning curve effect (as was done in previous studies).

A total of 5,493 treatments were performed between May 2020 and December 2023, ranging between 1 to 499 treatments per patient, with 76.1% of patients conducting 4 or more treatments. The treatments distribution for children is presented in Table 2 and compared to the device usage distribution in the rest of real-world Nerivio users during the same time period.

# of treatments‍per patient1-34-67-910-1213-1516-18>18Children  (6-11 years old, N=293)70  (23.9%)46  (15.7%)29  (9.9%)35  (11.9%)18  (6.1%)19  (6.5%)76  (25.9%)Adolescents (12-18 years old, N=1,628)630  (38.7%)385  (23.6%)205  (12.6%)158  (9.7%)52  (3.2%)47  (2.9%)152  (9.3%)Adults (≥18 years old, N=12,151)4696  (38.6%)2599  (21.4%)1497  (12.3%)1431  (11.8%)333  (2.7%)261  (2.1%)1334  (11.0%)

Table 2 – Nerivio usage distribution (treatments per patient) from May 2020 to December 2023

Safety

No device-related adverse events were reported by the 293 participants. An additional analysis assessed the number of customer support inquiries (general and device-related) made by this patient cohort (usually through their parents), Overall,121 general inquires and 21 device-related inquiries were submitted by the children population, resulted as inquires rates of 0.43 and 0,072, respectively, compared to inquires rates of 0.37 and 0,67 in all other Nerivio users. Demonstrating similar inquiry rate for children and all other users (p=0.725).

Efficacy

Consistency for headache relief and freedom from headache at 50% of the treatments Consistent headache relief was reported by 72.2% (13/18) of the patients with available data, and freedom from headache was reported by 36.0% (9/25). As can be seen in Table 3, the results for consistent headache relief and freedom in children are similar to the results from prior clinical trial in adolescents (TCH004), which showed consistent headache relief in 66.7% (26/39) and consistent headache freedom in 33.3% (13/39) of the adolescent study population. There are no statistically significant differences between the children and adolescents for consistent headache relief and freedom.

In addition, these results are in agreement, or slightly better numerically, with the results for consistency of headache relief and freedom from headache found in real-world data from adults and adolescents. In adolescents, it was shown that 60.3% (158 of 262) and 26.3% (76 of 289) experienced headache relief or freedom from headache in at least 50% of their treatments, respectively. It was shown that 55.6% (6,519 of 11,723) and 20.3% (3,021 of 14,854) of the adults experienced headache relief or freedom from headache in at least 50% of their treatments, respectively.

Children (age 6-121) NCT06138756Adolescents (age 12-17) NCT04089761Chi^2P valueConsistent headache relief ^aat 2 hours post-treatment72.2% (13/18)66.7% (26/39)0.1750.674Consistent headache freedom ^b at 2 hours post-treatment36.0% (9/25)33.3% (13/39)0.0480.826

Table 3 – Effectiveness of Nerivio at achieving consistent headache relief/freedom and in children compared to adolescents.

Consistency for functional disability relief and freedom from functional disability at 50% of the treatments

Functional disability relief and functional disability freedom were reported by 83.3% (15/18) and 38.9% (7/18) of the participants, respectively. As can be seen in Table 4 the results for functional disability relief and freedom are similar to the functional disability relief (69.7% [23/33]) and functional disability freedom (39.4% [13/33]) demonstrated by treating with the Nerivio device in the adolescent population.

In addition, these results are in agreement with the results for consistency of functional disability relief and freedom from functional disability found in real-world data from adolescents and adults. In adolescents, it was shown that 66.3% (169 of 255) and 41.2% (105 of 255) experienced functional disability relief or freedom from functional disability in at least 50% of their treatments, respectively.In adults, It was shown that 51.2% (6,731 of 13,156) and 24.9% (3,272 of 13,156) of the adults experienced functional disability relief or freedom from functional disability in at least 50% of their treatments, respectively.

Children‍(ages 6-11) RWE-009Adolescents (ages 12-17)‍TCH004Chi^2P valueConsistent functional disabilityrelief ^c at 2 hours post-treatment83.3% (15/18)69.7% (23/33)0.0330.285Consistent functional disability freedom ^d at 2 hourspost-treatment38.9% (7/18)39.4% (13/33)0.0010.971

Table 4 – Effectiveness of Nerivio at achieving consistent headache relief/freedom and functional disability relief/freedom in children compared to adolescents.
^c Defined as decrease (improvement) by at least one level of functional disability from baseline^d Defined as decrease from any disability level at baseline to none Consistency for freedom from migraine associated symptoms at 50% of the treatments Consistent 2-hours post-treatment freedom from migraine associated symptoms in at least 50% of the treatments per participant in which the participant reported an associated symptom(s) at baseline was 70.0% (7/10) for nausea/vomiting, 50.0% (4/8) for phonophobia, and 22.2% (2/9) for photophobia. As can be seen in Table 7, these results are in agreement with the freedom from migraine associated symptom(s) found in the adolescent’s population.

Children (ages 6-11) RWE-009Adolescents (ages 12-17) TCH004Chi^2P valueConsistent freedom from nausea/ vomiting at 2 hours post-treatment70.0% (7/10)54.5% (12/22)0.6800.409Consistent freedom from phonophobia at 2 hours post-treatment50.0% (4/8)40.0% (10/25)0.2480.618Consistent freedom from photophobia at 2 hours post-treatment22.2% (2/9)41.9% (13/31)0.2150.642

Table 5 – Effectiveness of Nerivio at achieving consistent freedom from migraine associated symptoms in children compared to adolescents.

Conclusions

The current results align with previous clinical trials and real-world evidence in adolescents and adults confirming the efficacy, tolerability, and safety of Nerivio device in the treatment of acute migraine, showing no adverse events and high efficacy in children

The safety results demonstrate a high safety and tolerability profile, with no reporting of device-related adverse events.

The stimulation intensity applied by the vast majority of the young patients is at a level that is sufficient for obtaining an effective treatment and is very similar to the intensity distribution demonstrated by adolescents in previous studies. In terms of efficacy, the clinical outcome for acute treatment of migraine shown in this study for this young age group is the same as previously shown for older age groups, across all endpoints – pain relief and disappearance, disappearance of associated symptoms, and partial or complete relief from functional disability.

The current results may suggest an additional non-pharmacological therapeutic tool for children, which is thought to be important in improving their quality of life.

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