Tricaprilin Infantile Spasms Pilot Study

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability, and efficacy of tricaprilin in subjects with infantile spasms. This is a single-arm, open-label, pilot study in up to 10 subjects with infantile spasms. Upon completion of the main phase, subjects who exhibit improvement in seizure control and who tolerate the compound will be offered continued use of the IMP until benefit-risk ratio is no longer favourable, in a one-year open-label extension phase, available to Australian participants only.

Official Title
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A Phase I Open-Label Pilot Study to Investigate the Feasibility, Safety, Tolerability and Efficacy of Daily Administration of Tricaprilin in Subjects With Infantile Spasms

Conditions
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Infantile Spasm

Intervention / Treatment
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* Drug: Tricaprilin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female infants ages 3 months to 24 months, inclusive, at the time of parent/legal guardian signing the informed consent Clinical diagnosis of IS, confirmed by analysis of a 24-hour video-electroencephalogram (vEEG) recording, including at least one documented spasm Continued infantile spasms despite adequate treatment with oral prednisolone (or adrenocorticotropic hormone [ACTH]) and vigabatrin If being treated with concomitant ASDs (other than ketogenic therapies/diet), current ASDs have been at a constant daily dose for at least 1 week. Subject is taking no more than 3 concomitant ASDs Exclusion Criteria: Subject considered by the Investigator, for any reason, to be an unsuitable candidate to receive the investigational product Significant and active pre-existing cardiovascular, renal, liver, infectious, or other systemic disease Subject has clinically significant renal impairment Clinically significant abnormality on ECG that, in the opinion of the Investigator, increases the safety risks of participating in the study Known or suspected allergy to the investigational product Known history of aspiration pneumonia within the past year Previous participation in another clinical study of the investigational product or received any investigational drug, device, or therapy within 30 days of study entry or within five half-lives of another investigational drug Within 14 days of screening, subject has: received therapy with felbamate, cannabinoids, ketogenic diet, or vagus nerve stimulation received therapy with ACTH, prednisolone or other steroid Pre-existing lethal or potentially lethal condition other than infantile spasms Previous failure to respond to an appropriate trial (at least 2 weeks) of the ketogenic diet

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 36 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tricaprilin<br>Tricaprilin will be administered for 5-21 days. The total daily dose (individual per subject up to a maximum of 10g/kg/day) will be split into 4 doses administered orally, approximately every 6 hours. | Drug: Tricaprilin<br>* Tricaprilin will be emulsified in infant formula/milk<br>* Other names: AC-OL-01;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the safety of daily administration of tricaprilin in subjects with Infantile Spasms (IS) | Treatment emergent adverse events | Up to end of study (Day 5 to 21; depending on subject) | 
| To determine the safety and tolerability of daily administration of tricaprilin in subjects with Infantile Spasms (IS) | Brussels Infant and Toddler Stool Scale; the scale consists of 4 categories: hard, formed, loose or watery. The category of stools per subject will be compared between baseline and during the study. | Up to end of study (Day 5 to 21; depending on subject) | 
| Extension Phase (for Australian sites only): To determine the safety of daily long-term administration of tricaprilin in subjects with Infantile Spasms (IS) | Treatment emergent adverse events | End of main phase treatment period to end of extension phase (1-year period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in spasm frequency based on caregiver spasm/seizure diary | Number of clusters and mean cluster duration | Baseline (1-week period) to end of treatment period (1-week period) | 
| Change in spasm frequency based on 24-hour video-EEG | Number of clusters and mean cluster duration | Baseline (1-week period) to end of treatment period (1-week period) | 
| Extension Phase (for Australian sites only): Change in spasm frequency based on caregiver spasm/seizure diary | Number of clusters and mean cluster duration | End of main phase treatment period to end of extension phase (1-year period) |