Trial Outcomes & Findings for Individualizing Dose of Growth Hormone to Maintain Normal Growth Velocity After Fulfilled Catch up Growth in Children (NCT NCT02879747)

Results Overview

The proportion of children in the intervention 1 group (=reduced dose) that maintained an individual ΔheightSDS within ±0.3 during the first year of the Maintenance trial, compared to the proportion of children in the intervention 2 group (non-reduced dose)

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

99 participants

Primary outcome timeframe

twelve months

Results posted on

2019-04-30

Participant Flow

All children in the fix dose group and children in the individualized dose group who have reached their midparental height SDS (\>- 0.6 SDS) during at least two years of GH-treatment within the 'GH-dose-catch up' study (TR 98-0198-003) and still are prepubertal were eligible in the study.

If glucose levels at the day of inclusion were higher than 7.1 mmol/L, then the child was excluded before assignment.

Participant milestones

Participant milestones
Measure	Decreased GH Dose Decreased GH dose Genotropin Genotropin: Children were randomized to 50% GH dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Unchanged GH Dose Unchanged GH dose Genotropin: Children were randomized to unchanged dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Control Group Control Group with informed consent but not randomized
Overall Study STARTED	27	38	33
Overall Study COMPLETED	23	32	31
Overall Study NOT COMPLETED	4	6	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Individualizing Dose of Growth Hormone to Maintain Normal Growth Velocity After Fulfilled Catch up Growth in Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Decreased GH Dose n=27 Participants Reduced dose 50% Genotropin Genotropin: Children were randomized to decreased GH dose by 50% after 2-3 years of Catch-up growth	Unchanged GH Dose n=38 Participants Unchanged dose Genotropin Genotropin: Children were randomized to unchanged GH dose after 2-3 years of Catch-up growth	Control Group n=33 Participants Control Group randomized in the previous study to fix dose. This group of children continued with fix dose in the current trial after signing informed consent.	Total n=98 Participants Total of all reporting groups
Age, Categorical <=18 years	27 Participants n=5 Participants	38 Participants n=7 Participants	33 Participants n=5 Participants	98 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	8.53 years STANDARD_DEVIATION 1.51 • n=5 Participants	8.52 years STANDARD_DEVIATION 2.11 • n=7 Participants	8.33 years STANDARD_DEVIATION 1.78 • n=5 Participants	8.52 years STANDARD_DEVIATION 1.99 • n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	26 Participants n=4 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	27 Participants n=7 Participants	25 Participants n=5 Participants	72 Participants n=4 Participants
Region of Enrollment Sweden	27 participants n=5 Participants	38 participants n=7 Participants	33 participants n=5 Participants	65 participants n=4 Participants

PRIMARY outcome

Timeframe: twelve months

The proportion of children in the intervention 1 group (=reduced dose) that maintained an individual ΔheightSDS within ±0.3 during the first year of the Maintenance trial, compared to the proportion of children in the intervention 2 group (non-reduced dose)

Outcome measures

Outcome measures
Measure	Decreased GH Dose n=27 Participants Decreased GH dose Genotropin Genotropin: Children were randomized to 50% GH dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Interventional 2 n=38 Participants Unchanged GH dose Genotropin: Children were randomized to unchanged dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Control Group n=33 Participants Control Group children with fix dose through the previous and current trial and with signed consent
The Proportion of Children Maintaining Normal Growth Velocity	23 Participants	32 Participants	31 Participants

SECONDARY outcome

Timeframe: start of study to two years after start in the trial

Population: Drop outs due to puberty or adverse events

Delta Insulin-like growth factor-I (24 months after start compared to start of study) expressed as ng/ml and converted to standard deviation scores (SDS) to adjust for gender and age. A standard deviation score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A mean value within +-0.5 SDS and a range within +-1.0 SDS is a favorable outcome.

Outcome measures

Outcome measures
Measure	Decreased GH Dose n=15 Participants Decreased GH dose Genotropin Genotropin: Children were randomized to 50% GH dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Interventional 2 n=22 Participants Unchanged GH dose Genotropin: Children were randomized to unchanged dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Control Group n=23 Participants Control Group children with fix dose through the previous and current trial and with signed consent
IGF-I	-1.10 standard deviation scores Standard Deviation 1.14	0.58 standard deviation scores Standard Deviation 0.91	-0.06 standard deviation scores Standard Deviation 1.26

SECONDARY outcome

Timeframe: 1-7 years in the trial

Population: All 98 Children were measured at start of puberty

Height at start of puberty measured as cm and expressed as standard deviation score (SDS) to adjust for age and gender

Outcome measures

Outcome measures
Measure	Decreased GH Dose n=27 Participants Decreased GH dose Genotropin Genotropin: Children were randomized to 50% GH dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Interventional 2 n=38 Participants Unchanged GH dose Genotropin: Children were randomized to unchanged dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Control Group n=33 Participants Control Group children with fix dose through the previous and current trial and with signed consent
Height SDS at Start of Puberty	-1.0 standard deviation scores Standard Deviation 1.02	-1.06 standard deviation scores Standard Deviation 0.84	-0.98 standard deviation scores Standard Deviation 0.91

OTHER_PRE_SPECIFIED outcome

Timeframe: start of study to two years after start in the trial

Changes in height standard deviation scores (SDS) (calculated as height in cm at start converted to SDS and height in cm after two years in the trial converted to SDS)

Outcome measures

Outcome measures
Measure	Decreased GH Dose n=15 Participants Decreased GH dose Genotropin Genotropin: Children were randomized to 50% GH dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Interventional 2 n=22 Participants Unchanged GH dose Genotropin: Children were randomized to unchanged dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Control Group n=23 Participants Control Group children with fix dose through the previous and current trial and with signed consent
Changes in Height	0.18 standard deviation scores Standard Deviation 0.16	0.57 standard deviation scores Standard Deviation 0.36	0.55 standard deviation scores Standard Deviation 0.26

Adverse Events

Decreased GH Dose

Serious events: 3 serious events

Other events: 20 other events

Deaths: 0 deaths

Unchanged GH Dose

Serious events: 4 serious events

Other events: 25 other events

Deaths: 0 deaths

Control Group

Serious events: 3 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Decreased GH Dose n=27 participants at risk Reduced dose 50% Genotropin Children were randomized to decreased GH dose by 50% after 2-3 years of Catch-up growth	Unchanged GH Dose n=38 participants at risk Unchanged dose Children were randomized to unchanged dose after 2-3 years of Catch-up growth	Control Group n=33 participants at risk Control Group with fix dose. Children that were randomized to fix dose in the previous and current trial and signed informed consent
Ear and labyrinth disorders Otitis media	3.7% 1/27 • Number of events 1 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	0.00% 0/38 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	0.00% 0/33 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.
Gastrointestinal disorders Abdominal pain	3.7% 1/27 • Number of events 1 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	2.6% 1/38 • Number of events 1 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	0.00% 0/33 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.
Infections and infestations facial nerve palsy due to tick disease	3.7% 1/27 • Number of events 1 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	0.00% 0/38 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	0.00% 0/33 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.
Injury, poisoning and procedural complications accident	0.00% 0/27 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	2.6% 1/38 • Number of events 1 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	0.00% 0/33 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.
Injury, poisoning and procedural complications fracture	0.00% 0/27 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	5.3% 2/38 • Number of events 2 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	3.0% 1/33 • Number of events 1 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.
Infections and infestations Urinary tract infection (upper)	0.00% 0/27 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	0.00% 0/38 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	6.1% 2/33 • Number of events 2 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.

Other adverse events

Other adverse events
Measure	Decreased GH Dose n=27 participants at risk Reduced dose 50% Genotropin Children were randomized to decreased GH dose by 50% after 2-3 years of Catch-up growth	Unchanged GH Dose n=38 participants at risk Unchanged dose Children were randomized to unchanged dose after 2-3 years of Catch-up growth	Control Group n=33 participants at risk Control Group with fix dose. Children that were randomized to fix dose in the previous and current trial and signed informed consent
Infections and infestations virosis	74.1% 20/27 • Number of events 52 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	65.8% 25/38 • Number of events 46 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.	72.7% 24/33 • Number of events 53 • Two years or in some cases up to seven prepubertal years No relevant information according to reviewer.

Additional Information

Dr Jovanna Dahlgren, PI and director of Department of Pediatrics

Queen Silvia Children´s Hospital and University of Gothenburg

Phone: +46702750233

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place