Turner's Syndrome
Conditions
Keywords
Growth hormone, Turner syndrome, r-hGH, early treatment
Brief summary
The objective of this study is to evaluate the efficacy and safety of recombinant human growth hormone (r-hGH) treatment in girls with Turner Syndrome under the age of 4 years. After 4 years of treatment, height in these girls will be compared with an historical control group of untreated girls with Turner Syndrome, matched for age and height at baseline.
Interventions
DRUGr-hGH
Subcutaneous administration.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
No minimum to 4 Years
Healthy volunteers
No
Inclusion criteria
* Young girls with turner syndrome proved by karyotype * Growth hormone secretion confirmed with ornithin stimulation test * Normal glucidic metabolism confirmed by assessment of HbA1c * None associated severe pathology which could have impact on growth (i.e. renal insufficiency, decompensated heart failure) * No previous or associated treatment with anabolic or sexual steroids * Known parental height
Exclusion criteria
* Severe associated pathology with impact on growth * Concomitant treatment with impact on growth * Previous or associated treatment with anabolic steroids * Associated growth hormone deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Height SDS at Year 4 | Year 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Abnormal Glycated Hemoglobin (HbA1c) Levels | 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. |
| Difference Between Bone Age (BA) and Chronological Age (CA) (BA-CA) | Baseline, Year 1, Year 2 | 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. |
| Number of Participants With Anti r-hGH Antibodies | Baseline up to Year 2 | — |
| Number of Participants With Abnormal Insulin-Like Growth Factor 1 (IGF1) Levels | Baseline up to Year 2 | 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. |
| Number of Participants Who Reached Normal Height at Year 4 | Year 4 | 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. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| r-hGH 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. | 64 |
| 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. | 51 |
| Total | 115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Enrolled But Not Treated | 3 | 0 |
Baseline characteristics
| Characteristic | r-hGH | Historical Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 64 Participants | 51 Participants | 115 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 64 Participants | 51 Participants | 115 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 61 |
| serious Total, serious adverse events | 8 / 61 |
Outcome results
Primary
Height SDS at Year 4
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.
Time frame: Year 4
Population: All treated participants from r-hGH arm and all participants from Historical Control arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-hGH | Height SDS at Year 4 | -1.35 standard deviation score | Standard Deviation 0.86 |
| Historical Control | Height SDS at Year 4 | -2.44 standard deviation score | Standard Deviation 0.73 |
Secondary
Difference Between Bone Age (BA) and Chronological Age (CA) (BA-CA)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| r-hGH | Difference Between Bone Age (BA) and Chronological Age (CA) (BA-CA) | Baseline | -8.9 months | Standard Deviation 7.5 |
| r-hGH | Difference Between Bone Age (BA) and Chronological Age (CA) (BA-CA) | Year 1 | -8.7 months | Standard Deviation 6.5 |
| r-hGH | Difference Between Bone Age (BA) and Chronological Age (CA) (BA-CA) | Year 2 | -8.1 months | Standard Deviation 7.8 |
Secondary
Number of Participants Who Reached Normal Height at Year 4
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.
Time frame: Year 4
Population: All treated participants from r-hGH arm. This outcome measure was only planned in the r-hGH arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| r-hGH | Number of Participants Who Reached Normal Height at Year 4 | 49 participants |
Secondary
Number of Participants With Abnormal Glycated Hemoglobin (HbA1c) Levels
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.
Time frame: Baseline up to Year 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| r-hGH | Number of Participants With Abnormal Glycated Hemoglobin (HbA1c) Levels | 1 participants |
Secondary
Number of Participants With Abnormal Insulin-Like Growth Factor 1 (IGF1) Levels
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.
Time frame: Baseline up to Year 2
Population: All treated participants from r-hGH arm. This outcome measure was only planned in the r-hGH arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| r-hGH | Number of Participants With Abnormal Insulin-Like Growth Factor 1 (IGF1) Levels | 46 participants |
Secondary
Number of Participants With Anti r-hGH Antibodies
Time frame: Baseline up to Year 2
Population: Data for this outcome was not collected from any participant.