Treatment of Adrenal Insufficiency in Children

Study Overview
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Brief Summary
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The study will be conducted in a total of 24 subjects before their 6th birthday, requiring replacement therapy for adrenal insufficiency due to either CAH, primary adrenal failure or hypopituitarism. The study will consist of three consecutive cohorts. Cohort 1 will include 12 subjects aged between 2 and < 6 years. If no safety concerns emerge, then 6 subjects aged 28 days to <2 years will be enrolled (Cohort 2). A review of accumulated data will be undertaken and only if again no safety concerns emerge, then 6 neonates aged from birth to <28 days will be enrolled (Cohort 3). The decision to continue after each cohort will be based on the recommendation of an Independent Data Monitoring Committee (IDMC).

Detailed Description
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This is a Phase 3, open label, single centre study of Infacort® in neonates, infants and children less than 6 years of age with adrenal insufficiency. The study will be conducted in a total of 24 subjects, before their 6th birthday, requiring replacement therapy for adrenal insufficiency due to either CAH, primary adrenal failure or hypopituitarism. Due to the rare occurrence of adrenal insufficiency it is expected that for the third cohort of this study (neonates) only subjects with CAH will be recruited. The study will consist of three consecutive parts. Cohort 1 will include 12 subjects aged between 2 and < 6 years. If no safety concerns emerge, then 6 subjects aged 28 days to <2 years will be enrolled (Cohort 2). A review of accumulated data will be undertaken and only if again no safety concerns emerge, then 6 neonates aged from birth to <28 days will be enrolled (Cohort 3). The decision to continue after each cohort will be based on the recommendation of an Independent Data Monitoring Committee (IDMC). The study will consist of a screening visit (Visit 1 performed as a minimum the day before the intake of study drug), one treatment visit (Visit 2, Day 1), a follow-up visit (Visit 3) one to three days after intake of study drug (Day 2, Day 3 or Day 4) and a follow-up telephone call (Visit 4) 7 - 10 days after intake of study drug. Study completion evaluation will be performed at Visit 3. Parents/ carers will have at least 1 night to consider participation of their child before completing written informed consent. Children aged 3 - 6 years will be informed about their involvement in the study in the presence of their parents/carers. All subjects will receive their standard treatment including fludrocortisone other than the dose of hydrocortisone that is to be substituted by Infacort®. Subjects who meet the eligibility criteria at screening (Visit 1) will attend for Visit 2 at a suitable time before the next planned dose of hydrocortisone is due. Subjects may have insertion of an intravenous cannula (with suitable local anaesthesia) allowing blood samples to be taken as well as their routine clinical samples (where required) prior to their next dose of hydrocortisone given as Infacort®. If a cannula is not used, direct venous sampling may be carried out instead. After all planned study procedures have been completed the subjects will go home and will return one to three days later for the follow-up assessments (Visit 3). A follow-up telephone call (Visit 4) 7 - 10 days after intake of study drug will be undertaken.

Official Title
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A Phase 3 Open-label Study of Infacort® in Neonates, Infants and Children Less Than 6 Years of Age With Adrenal Insufficiency

Conditions
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Adrenal Insufficiency

Intervention / Treatment
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* Drug: Infacort®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female children less than 6 years of age. A diagnosis of adrenal insufficiency as confirmed by an inappropriately low cortisol usually with other supporting tests. Receiving appropriate adrenocortical replacement therapy (hydrocortisone with/without fludrocortisone). Adequately hydrated and nourished. Ability of parents/carers to understand and give written Informed Consent Exclusion Criteria: Clinically evident acute adrenal insufficiency (adrenal crisis). Inability of the child to take oral therapy. Concomitant therapy (other than that required to treat adrenal insufficiency, Vitamin D, Fluoride, Thyroxine and growth hormone). Subjects with clinical signs of acute infection or fever on Day 1. Any surgical or medical condition which in the opinion of the investigator may place the subject at higher risk from his/her participation in the study. Parents/carers of subjects unwilling to consent to saving and propagation of pseudonymised medical data for study reasons. Subjects who are dependent on the investigator or the sponsor.

Ages Eligible for Study
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Minimum Age: 1 Week
Maximum Age: 6 Years

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: Infacort<br>Infacort® is a dry granule formulation of hydrocortisone stored in capsules that will be available in different strengths (0.5, 1.0, 2.0 and 5.0mg). The clinically-appropriate dose, based on standard individualised treatment, will be administered, given as a single dose orally. This will usually be equivalent to the previous day's dose. | Drug: Infacort®<br>* dry granule formulation of hydrocortisone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Cortisol Concentration up to 240 Minutes | The primary endpoint will be the maximum levels of serum cortisol concentration up to 240 minutes after intake of study drug as determined by the central laboratory. | 240 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Cortisol Concentration up to 6 Hours | Serum cortisol concentration 240 minutes after intake of study drug as determined by the central laboratory | 240 minutes | 
| Subject Assessment of Taste of the Product | Palatability of the investigational product as determined by parent/carer responses to the following questions: Question 1: My child found swallowing easy. Question 2: My child showed a positive reaction after Infacort was given. Question 3: I would be happy to give my child Infacort in the future. Question 4: Overall, I would prefer Infacort for my child over the usual hydrocortisone medication. | 1 minute | 
| Incidence of Serious Adverse Events (SAEs) and Adverse Events (AE) | Incidence of serious adverse events (SAEs) and adverse events (AE). | 7-10 days |