Extension Study for Patients Entered Into Study Infacort 003

Phase 3

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Infacort	Infacort®	Infacort® granules

Primary Outcome Measures

Name	Time	Method
Incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs)	29 months	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.

Secondary Outcome Measures

Name	Time	Method
Growth Velocity	29 months	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.
Cortisol Levels	29 months	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).
Number of Participants Exhibiting a Change in Tanner Development Stage	29 months	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).