Adrenal Insufficiency
Conditions
Brief summary
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
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.
Interventions
DRUGInfacort®
dry granule formulation of hydrocortisone
Sponsors
Treatment of Adrenal Insufficiency in Neonates consortium (TAIN)
Neurocrine UK Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Weeks to 6 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female children less than 6 years of age. 2. A diagnosis of adrenal insufficiency 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. 5. Ability of parents/carers to understand and give written Informed Consent
Exclusion criteria
1. Clinically evident acute adrenal insufficiency (adrenal crisis). 2. Inability of the child to take oral therapy. 3. Concomitant therapy (other than that required to treat adrenal insufficiency, Vitamin D, Fluoride, Thyroxine and growth hormone). 4. Subjects with clinical signs of acute infection or fever on Day 1. 5. 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. 6. Parents/carers of subjects unwilling to consent to saving and propagation of pseudonymised medical data for study reasons. 7. Subjects who are dependent on the investigator or the sponsor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Cortisol Concentration up to 240 Minutes | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Cortisol Concentration up to 6 Hours | 240 minutes | Serum cortisol concentration 240 minutes after intake of study drug as determined by the central laboratory |
| Subject Assessment of Taste of the Product | 1 minute | 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. |
| Incidence of Serious Adverse Events (SAEs) and Adverse Events (AE) | 7-10 days | Incidence of serious adverse events (SAEs) and adverse events (AE). |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Infacort 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.
Infacort®: dry granule formulation of hydrocortisone | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Infacort |
|---|---|
| Age, Categorical <=18 years | 24 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 718.1 days |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 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 | 24 Participants |
| Region of Enrollment Germany | 24 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 8 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
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.
Time frame: 240 minutes
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Infacort | Serum Cortisol Concentration up to 240 Minutes | 575.8 nmol/L | Geometric Coefficient of Variation 47.9 |
Secondary
Incidence of Serious Adverse Events (SAEs) and Adverse Events (AE)
Incidence of serious adverse events (SAEs) and adverse events (AE).
Time frame: 7-10 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infacort | Incidence of Serious Adverse Events (SAEs) and Adverse Events (AE) | Severe TEAEs | 0 Adverse Events |
| Infacort | Incidence of Serious Adverse Events (SAEs) and Adverse Events (AE) | Moderate TEAEs | 2 Adverse Events |
| Infacort | Incidence of Serious Adverse Events (SAEs) and Adverse Events (AE) | Mild TEAEs | 10 Adverse Events |
| Infacort | Incidence of Serious Adverse Events (SAEs) and Adverse Events (AE) | Treatment-Emergent | 12 Adverse Events |
| Infacort | Incidence of Serious Adverse Events (SAEs) and Adverse Events (AE) | Serious TEAEs | 0 Adverse Events |
Secondary
Serum Cortisol Concentration up to 6 Hours
Serum cortisol concentration 240 minutes after intake of study drug as determined by the central laboratory
Time frame: 240 minutes
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Infacort | Serum Cortisol Concentration up to 6 Hours | 60.1 nmol/L | Geometric Coefficient of Variation 131.7 |
Secondary
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.
Time frame: 1 minute
Population: Out of the total population, one parent/carer did not complete the palatability questionnaire and one parent/carer did not complete questions 3 and 4, and thus were excluded from the analysis of the relevant questions.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Infacort | Subject Assessment of Taste of the Product | 19 Participants |
| Question 2 | Subject Assessment of Taste of the Product | 15 Participants |
| Question 3 | Subject Assessment of Taste of the Product | 21 Participants |
| Question 4 | Subject Assessment of Taste of the Product | 21 Participants |