Trial Outcomes & Findings for Growth Hormone Treatment for the Prevention of Short Stature in Young Girls With Turner Syndrome Before the Age of 4 Years (NCT NCT01066052)

NCT ID: NCT01066052

Last Updated: 2018-12-14

Results Overview

Height SDS was calculated as height minus reference mean height divided by standard deviation of the reference population. Height SDS reflects the height relative to a reference population of the same age and gender.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 115 participants
• Primary outcome timeframe: Year 4
• Results posted on: 2018-12-14

Participant Flow

Participant milestones

Measure	Recombinant Human Growth Hormone (r-hGH) Participants (girls) received r-hGH (Saizen®) as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received depended on participants' baseline height standard deviation score (SDS) relative to the general population standard: participants with a height SDS of -2 standard deviation (SD) or lower received 0.05 milligrams per kilogram (mg/kg) per day r-hGH and those with a height SDS between -1 and -2 SD received 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants received a fixed dose of 0.05 mg/kg per day for a further 2 years.	Historical Control This arm included matching (age and height) historical control participants (girls) with turner syndrome, who were born between 1961 and 1990 and were untreated.
Overall Study STARTED	64	51
Overall Study Treated	61	0
Overall Study COMPLETED	61	51
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Measure	Recombinant Human Growth Hormone (r-hGH) Participants (girls) received r-hGH (Saizen®) as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received depended on participants' baseline height standard deviation score (SDS) relative to the general population standard: participants with a height SDS of -2 standard deviation (SD) or lower received 0.05 milligrams per kilogram (mg/kg) per day r-hGH and those with a height SDS between -1 and -2 SD received 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants received a fixed dose of 0.05 mg/kg per day for a further 2 years.	Historical Control This arm included matching (age and height) historical control participants (girls) with turner syndrome, who were born between 1961 and 1990 and were untreated.
Overall Study Enrolled But Not Treated	3	0

Baseline Characteristics

Growth Hormone Treatment for the Prevention of Short Stature in Young Girls With Turner Syndrome Before the Age of 4 Years

Baseline characteristics by cohort

Measure	r-hGH n=64 Participants Participants (girls) received r-hGH as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received depended on participants' baseline height SDS relative to the general population standard: participants with a height SDS of -2 SD or lower received 0.05 mg/kg per day r-hGH and those with a height SDS between -1 and -2 SD received 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants received a fixed dose of 0.05 mg/kg per day for a further 2 years.	Historical Control n=51 Participants This arm included matching (age and height) historical control participants (girls) with turner syndrome, who were born between 1961 and 1990 and were untreated.	Total n=115 Participants Total of all reporting groups
Age, Categorical <=18 years	64 Participants n=5 Participants	51 Participants n=7 Participants	115 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	51 Participants n=7 Participants	115 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Year 4

Population: All treated participants from r-hGH arm and all participants from Historical Control arm.

Height SDS was calculated as height minus reference mean height divided by standard deviation of the reference population. Height SDS reflects the height relative to a reference population of the same age and gender.

Outcome measures

Measure	r-hGH n=61 Participants Participants (girls) received r-hGH as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received depended on participants' baseline height SDS relative to the general population standard: participants with a height SDS of -2 SD or lower received 0.05 mg/kg per day r-hGH and those with a height SDS between -1 and -2 SD received 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants received a fixed dose of 0.05 mg/kg per day for a further 2 years.	Historical Control n=51 Participants This arm included matching (age and height) historical control participants (girls) with turner syndrome, who were born between 1961 and 1990 and were untreated.
Height SDS at Year 4	-1.35 standard deviation score Standard Deviation 0.86	-2.44 standard deviation score Standard Deviation 0.73

SECONDARY outcome

Timeframe: Baseline up to Year 2

HbA1c develops when hemoglobin, a protein within red blood cells that carries oxygen throughout the body, joins with glucose in the blood, becoming glycated. The higher the level of glucose in the blood, the higher the level of HbA1c is detectable on red blood cells. The normal range for HbA1c is 4 percent (%) to 5.9%. Number of participants, who had abnormal HbA1c levels any time during the assessment, were reported.

Outcome measures

Measure	r-hGH n=61 Participants Participants (girls) received r-hGH as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received depended on participants' baseline height SDS relative to the general population standard: participants with a height SDS of -2 SD or lower received 0.05 mg/kg per day r-hGH and those with a height SDS between -1 and -2 SD received 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants received a fixed dose of 0.05 mg/kg per day for a further 2 years.	Historical Control This arm included matching (age and height) historical control participants (girls) with turner syndrome, who were born between 1961 and 1990 and were untreated.
Number of Participants With Abnormal Glycated Hemoglobin (HbA1c) Levels	1 participants	—

SECONDARY outcome

Timeframe: Baseline, Year 1, Year 2

Population: All treated participants from r-hGH arm. This outcome measure was only planned in the r-hGH arm. Overall number of participants analyzed = participants with available data for this outcome; number analyzed = participants with available data for this outcome at specified timepoint.

BA was determined using left wrist and hand X-ray. CA was determined using the date of birth. Difference of BA and CA (BA-CA) was reported.

Outcome measures

Measure	r-hGH n=60 Participants Participants (girls) received r-hGH as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received depended on participants' baseline height SDS relative to the general population standard: participants with a height SDS of -2 SD or lower received 0.05 mg/kg per day r-hGH and those with a height SDS between -1 and -2 SD received 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants received a fixed dose of 0.05 mg/kg per day for a further 2 years.	Historical Control This arm included matching (age and height) historical control participants (girls) with turner syndrome, who were born between 1961 and 1990 and were untreated.
Difference Between Bone Age (BA) and Chronological Age (CA) (BA-CA) Baseline	-8.9 months Standard Deviation 7.5	—
Difference Between Bone Age (BA) and Chronological Age (CA) (BA-CA) Year 1	-8.7 months Standard Deviation 6.5	—
Difference Between Bone Age (BA) and Chronological Age (CA) (BA-CA) Year 2	-8.1 months Standard Deviation 7.8	—

SECONDARY outcome

Timeframe: Baseline up to Year 2

Population: Data for this outcome was not collected from any participant.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Year 2

Population: All treated participants from r-hGH arm. This outcome measure was only planned in the r-hGH arm.

The normal range for IGF1 levels is 45 to 117 nanogram per milliliter (ng/mL) for girls aged less than (<) 3 years and 80 to 236 ng/mL for girls aged 3 to 6 years. Values outside the normal range were considered abnormal. Number of participants, who had abnormal IGF1 levels any time during the assessment, were reported.

Outcome measures

Measure	r-hGH n=61 Participants Participants (girls) received r-hGH as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received depended on participants' baseline height SDS relative to the general population standard: participants with a height SDS of -2 SD or lower received 0.05 mg/kg per day r-hGH and those with a height SDS between -1 and -2 SD received 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants received a fixed dose of 0.05 mg/kg per day for a further 2 years.	Historical Control This arm included matching (age and height) historical control participants (girls) with turner syndrome, who were born between 1961 and 1990 and were untreated.
Number of Participants With Abnormal Insulin-Like Growth Factor 1 (IGF1) Levels	46 participants	—

SECONDARY outcome

Timeframe: Year 4

Population: All treated participants from r-hGH arm. This outcome measure was only planned in the r-hGH arm.

Participants with normal height were those who attained a height which was within +/- 2 height SDS of reference population standard. Height SDS was calculated as height minus reference mean height divided by standard deviation of the reference population. Height SDS reflects the height relative to a reference population of the same age and gender.

Outcome measures

Measure	r-hGH n=61 Participants Participants (girls) received r-hGH as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received depended on participants' baseline height SDS relative to the general population standard: participants with a height SDS of -2 SD or lower received 0.05 mg/kg per day r-hGH and those with a height SDS between -1 and -2 SD received 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants received a fixed dose of 0.05 mg/kg per day for a further 2 years.	Historical Control This arm included matching (age and height) historical control participants (girls) with turner syndrome, who were born between 1961 and 1990 and were untreated.
Number of Participants Who Reached Normal Height at Year 4	49 participants	—

Adverse Events

r-hGH

Serious events: 8 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Measure	r-hGH n=61 participants at risk Participants (girls) received r-hGH as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received depended on participants' baseline height SDS relative to the general population standard: participants with a height SDS of -2 SD or lower received 0.05 mg/kg per day r-hGH and those with a height SDS between -1 and -2 SD received 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants received a fixed dose of 0.05 mg/kg per day for a further 2 years.
Vascular disorders Urethral reflux	1.6% 1/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.
Surgical and medical procedures Trauma leading to scalp surgery	1.6% 1/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.
Skin and subcutaneous tissue disorders Measles	1.6% 1/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.
Nervous system disorders Serious otitis	1.6% 1/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.
Immune system disorders Immunoglobulin G4 deficiency	1.6% 1/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.
Respiratory, thoracic and mediastinal disorders Arterial hypertension	1.6% 1/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.
Congenital, familial and genetic disorders Chronic persistent cytolysis	1.6% 1/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.
Surgical and medical procedures Surgery to remove large mass (meningocele/benign cyst)	1.6% 1/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.
Surgical and medical procedures Transtympanic drainage tube placement	1.6% 1/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.
Surgical and medical procedures Tonsillectomy/adenoidectomy	1.6% 1/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.

Other adverse events

Measure

r-hGH n=61 participants at risk Participants (girls) received r-hGH as a subcutaneous injection administered by a parent in the evening. During Years 1-2, the dose of r-hGH received depended on participants' baseline height SDS relative to the general population standard: participants with a height SDS of -2 SD or lower received 0.05 mg/kg per day r-hGH and those with a height SDS between -1 and -2 SD received 0.035 mg/kg per day r-hGH. After 2 years of treatment, all participants received a fixed dose of 0.05 mg/kg per day for a further 2 years.

Infections and infestations Infection

77.0% 47/61 Adverse events were collected only from participants treated with r-hGH. No adverse event data collection occurred in Historical Control arm.

Additional Information

Merck KGaA Communication Center,

Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

Phone: 496151725200

Email: service@merckgroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place