Extension Study for Patients Entered Into Study Infacort 003

Study Overview
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Brief Summary
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A Phase 3, open-label, single-group, non-randomised, observational study of the safety and biochemical disease control of Infacort® in neonates, infants and children with adrenal insufficiency and congenital adrenal hyperplasia who had completed study Infacort 003. All subjects who had satisfactorily completed study Infacort 003 were offered the opportunity to take part in Infacort 004.

Detailed Description
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A Phase 3, open-label, single-group, non-randomised, observational study of the safety and biochemical disease control of Infacort® in neonates, infants and children with AI who had completed study Infacort 003 (EudraCT number 2014-002265-30). All subjects who had satisfactorily completed study Infacort 003 wiere offered the opportunity to participate in study Infacort 004 at or after their final visit of study Infacort 003. Subjects received the usual clinically-appropriate dose (since bioequivalence has been demonstrated with conventional hydrocortisone), as determined by the Investigator, which was administered according to usual clinical practice - generally 3 or 4 times a day. Subjects could continue to be treated in this study until they met the study withdrawal criteria, until Infacort® was commercially available locally (which has now been achieved), or until the Sponsor decided to discontinue the study.

Official Title
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Open-label, Long-term Follow-up of Safety and Biochemical Disease Control of Infacort® in Neonates, Infants and Children With Congenital Adrenal Hyperplasia and Adrenal Insufficiency Previously Enrolled in the Infacort 003 Study

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: Subjects successfully completing study Infacort 003, whose inclusion criteria were: Male and female children less than 6 years of age. A diagnosis of adrenal insufficiency (AI) 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. In addition, the parents/carers must be able to understand and give written Informed Consent for this extension study. Exclusion Criteria: Clinically evident acute AI (adrenal crisis) (Note: the subject can be re-evaluated for eligibility once the episode is over) Inability of the child to take oral therapy Subjects with clinical signs of acute infection or fever on inclusion (Note: the subject can be re-evaluated for eligibility once the episode is over) Any surgical or medical condition that 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 in a dependent relationship with the Investigator or the Sponsor

Ages Eligible for Study
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Minimum Age: 1 Month
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® granules | Drug: Infacort®<br>* Infacort® is a dry granule formulation of hydrocortisone stored in capsules available in different strengths (0.5, 1.0, 2.0 and 5.0 mg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs) | The primary endpoint was the nature and occurrence of serious adverse events (SAEs) and adverse events (AEs) observed throughout the study. AEs were recorded from the time of the first intake of Infacort until the final visit. | 29 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth Velocity | Growth velocity standard deviation score (SDS). Body height/length (cm) was obtained at each visit by specially trained paediatric endocrine nurses or physicians using standard calibrated auxological methods. | 29 months | 
| Cortisol Levels | Cortisol levels measured from dried blood spots. The dried blood spots were analysed for multi-steroids, including cortisol (all subjects). Blood spot absolute laboratory values for the safety population are presented. A dried blood spot sample was collected at the initial and final visits, every month for the first 2 months of the study and thereafter every 6 months (unless required after 3 months). | 29 months | 
| Number of Participants Exhibiting a Change in Tanner Development Stage | The Tanner Development Stage was assessed as an additional analysis in this study. All assessments (breast, genitalia, and pubic hair) were Grade 1 (pre-pubertal) at baseline, with only 1 subject (in Cohort 2) showing a change during the study. Subject 018 showed progression to Grade 2 in the pubic hair category (sparse, pigmented hair mainly on labia). | 29 months |