Adrenal Insufficiency
Conditions
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.
Interventions
DRUGInfacort®
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).
Sponsors
Neurocrine UK Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 6 Years
Healthy volunteers
No
Inclusion criteria
Subjects successfully completing study Infacort 003, whose inclusion criteria were: 1. Male and female children less than 6 years of age. 2. A diagnosis of adrenal insufficiency (AI) as confirmed by an inappropriately low cortisol usually with other supporting tests. 3. Receiving appropriate adrenocortical replacement therapy (hydrocortisone with/without fludrocortisone). 4. 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
1. Clinically evident acute AI (adrenal crisis) (Note: the subject can be re-evaluated for eligibility once the episode is over) 2. Inability of the child to take oral therapy 3. 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) 4. 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 5. Parents/carers of subjects unwilling to consent to saving and propagation of pseudonymised medical data for study reasons 6. Subjects who are in a dependent relationship with the Investigator or the Sponsor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infacort Infacort® granules
Infacort®: 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). This was a non-randomised, open-label, single-group study; all subjects who participated received Infacort. One subject was initially withdrawn from the study, but subsequently re-enrolled. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Infacort |
|---|---|
| Age, Categorical <=18 years | 18 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 1021.6 days STANDARD_DEVIATION 650.84 |
| Body Mass Index | 17.02 kg/m^2 STANDARD_DEVIATION 2.083 |
| Body Surface Area | 0.582 m^2 STANDARD_DEVIATION 0.1803 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment Germany | 18 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 14 / 18 |
| serious Total, serious adverse events | 3 / 18 |
Outcome results
Primary
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.
Time frame: 29 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infacort | Incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs) | Serious TEAEs | 9 adverse events |
| Infacort | Incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs) | Treatment-Emergent Adverse Events (TEAE) - Overall | 193 adverse events |
| Infacort | Incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs) | Severe TEAEs | 0 adverse events |
| Infacort | Incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs) | Moderate TEAEs | 42 adverse events |
| Infacort | Incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs) | Mild TEAEs | 151 adverse events |
Secondary
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).
Time frame: 29 months
Population: The reason why n=14 at Visit 1 is because of no result for Subjects 005, 010, 017 \& 018. N=12 at Final Visit due to 12 completers.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Infacort | Cortisol Levels | Visit 1 | 43.329 nmol/L | Standard Deviation 48.3217 |
| Infacort | Cortisol Levels | Final Visit | 22.022 nmol/L | Standard Deviation 27.1323 |
Secondary
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.
Time frame: 29 months
Population: Reference data for growth velocity is only available for patients \<=6 years old at time of assessment. Therefore n=2 \& not 4 for C1 at Month 11. Subject 001 was re-enrolled so no Visit 10 data available and, therefore, n=1 for C1 at Month 23.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Infacort | Growth Velocity | visit 6 - 11th Month | 0.6343 Standard Deviation Score | Standard Deviation 2.51996 |
| Infacort | Growth Velocity | Visit 10 - 23rd Month | 0.9214 Standard Deviation Score | Standard Deviation 1.88757 |
Secondary
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).
Time frame: 29 months
Population: 'Count of Participants' data below represents the number of subjects that exhibited a change from baseline in their Tanner Development Stage.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infacort | Number of Participants Exhibiting a Change in Tanner Development Stage | 1 Participants |