Idiopathic Growth Hormone Deficiency, Turner Syndrome
Conditions
Keywords
Growth Hormone Deficiency, Turner syndrome, Pharmacogenetics, Recombinant Human Growth Hormone therapy
Brief summary
PREDICT Validation is a validation pharmacogenetic trial. The purpose of this study is to confirm that some genes can be used to predict how well a subject diagnosed with idiopathic growth hormone deficiency (IGHD) or turner syndrome (TS) will respond to a treatment with recombinant human growth hormone (r-hGH).
Detailed description
This study is an open-label, interventional, retrospective, multicenter, international study, single-arm, non-randomized, and non-controlled study. The subject's trial participation includes a single visit. During the visit, subjects who give consent to participate in the trial will undergo blood sampling for genetic markers testing and retrospective data will be collected relative to the first year of the subject's r-hGH treatment. The r-hGH treatment followed by the subject is indicated the pediatric population, therefore most of the subjects included into the trial will be below 18 years old. This study is a non-investigational medicinal product (IMP) trial therefore no drug product data is provided.
Interventions
OTHERBlood sampling
Subjects with pre-established diagnosis of IGHD and TS and were treated with r-hGH therapy for 1 year, will be observed in this retrospective cohort study wherein blood sampling will performed for genotyping of the various genetic markers along with collection of retrospective data relative to the r-hGH treatment.
Sponsors
Merck Serono S.A., Geneva
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
* Pre-established diagnosis of IGHD or TS based on classical criteria with at least 1 year of r-hGH therapy and with Tanner stage 1 at treatment start * Retrospective availability of a complete set of clinical, auxological and biological parameters necessary for building the predictive model * Other protocol defined inclusion criteria could apply
Exclusion criteria
* Acquired growth hormone deficiency (GHD) * Any drug or disease that could affect growth during the first year of r-hGH treatment * Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Height at Year 1 | Baseline and Year 1 | Change from baseline in height at year 1 was one of the growth parameter to assess the first year growth response to r-hGH treatment. |
| Change From Baseline in Height Standard Deviation Score (SDS) at Year 1 | Baseline and Year 1 | 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. Change from baseline in height SDS at Year 1 was one of the growth parameter to assess the first year growth response to r-hGH treatment. |
| Height Velocity Standard Deviation Score (SDS) at Year 1 | Year 1 | Height velocity SDS was calculated as height velocity minus reference mean height velocity divided by standard deviation of the reference population. Height velocity SDS reflects the height velocity relative to a reference population of the same age and gender. Height velocity SDS at Year 1 was one of the growth parameter to assess the first year growth response to r-hGH treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the Contribution of Validated Genetic Markers to the Amplitude of First Year Growth Response to r-hGH Therapy in IGHD Children Using Growth Hormone Deficiency Kabi-Pharmacia International Growth Study (GHD KIGS) Predictive Model | Year 1 | GHD KIGS predictive model includes various clinical, auxological and biological markers which are as follows: maximum growth hormone (GH) response to provocation test; age at onset of therapy; birth weight SDS; average GH dose received during the first year of r-hGH therapy; height SDS at start of therapy; the difference between the pre-treatment height SDS of the subject and the mid parental height SDS; and weight SDS at start of therapy. |
| Evaluation of the Contribution of Validated Genetic Markers to the Amplitude of First Year Growth Response to r-hGH Therapy in TS Girls Using Turner Syndrome Kabi-Pharmacia International Growth Study (TS KIGS) Predictive Model | Year 1 | TS KIGS predictive model includes various clinical, auxological and biological markers which are as follows: maximum GH response to provocation test; age at onset of therapy; birth weight SDS; average GH dose received during the first year of r-hGH therapy; height SDS at start of therapy; the difference between the pre-treatment height SDS of the subject and the mid parental height SDS; and weight SDS at start of therapy. |
Countries
Argentina, Canada, Czechia, France, Germany, Italy, Spain, Sweden, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Idiopathic Growth Hormone Deficiency (IGHD) Cohort Participants with pre-established diagnosis of IGHD and were treated with recombinant human growth hormone (r-hGH) therapy for at least 1 year were observed in this retrospective cohort study wherein blood sampling was performed for genotyping of the various genetic markers along with collection of retrospective data relative to the r-hGH treatment. | 293 |
| Turner Syndrome (TS) Cohort Participants with pre-established diagnosis of TS and were treated with r-hGH therapy for at least 1 year were observed in this retrospective cohort study wherein blood sampling was performed for genotyping of the various genetic markers along with collection of retrospective data relative to the r-hGH treatment. | 132 |
| Total | 425 |
Baseline characteristics
| Characteristic | Idiopathic Growth Hormone Deficiency (IGHD) Cohort | Turner Syndrome (TS) Cohort | Total |
|---|---|---|---|
| Age, Customized Between 8 to 12 years | 84 participants | 31 participants | 115 participants |
| Age, Customized greater than (>) 12 years | 12 participants | 6 participants | 18 participants |
| Age, Customized less than (<) 8 years | 197 participants | 95 participants | 292 participants |
| Sex: Female, Male Female | 85 Participants | 132 Participants | 217 Participants |
| Sex: Female, Male Male | 208 Participants | 0 Participants | 208 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 293 | 0 / 132 |
Outcome results
Primary
Change From Baseline in Height at Year 1
Change from baseline in height at year 1 was one of the growth parameter to assess the first year growth response to r-hGH treatment.
Time frame: Baseline and Year 1
Population: FAS population included all the participants who had provided informed consent and had non-missing height at start (defined as within one month prior to treatment start date) and at 1 year (+/- 120 days) of r-hGH treatment and had pharmacogenomics data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idiopathic Growth Hormone Deficiency (IGHD) Cohort | Change From Baseline in Height at Year 1 | Baseline | 103.6 centimeter | Standard Deviation 18.1 |
| Idiopathic Growth Hormone Deficiency (IGHD) Cohort | Change From Baseline in Height at Year 1 | Change at Year 1 | 9.8 centimeter | Standard Deviation 2.7 |
| Turner Syndrome (TS) Cohort | Change From Baseline in Height at Year 1 | Baseline | 103.5 centimeter | Standard Deviation 16.3 |
| Turner Syndrome (TS) Cohort | Change From Baseline in Height at Year 1 | Change at Year 1 | 8.6 centimeter | Standard Deviation 2 |
Primary
Change From Baseline in Height Standard Deviation Score (SDS) at Year 1
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. Change from baseline in height SDS at Year 1 was one of the growth parameter to assess the first year growth response to r-hGH treatment.
Time frame: Baseline and Year 1
Population: FAS population included all the participants who had provided informed consent and had non-missing height at start (defined as within one month prior to treatment start date) and at 1 year (+/- 120 days) of r-hGH treatment and had pharmacogenomics data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Idiopathic Growth Hormone Deficiency (IGHD) Cohort | Change From Baseline in Height Standard Deviation Score (SDS) at Year 1 | Baseline | -2.60 standard deviation score | Standard Deviation 1.06 |
| Idiopathic Growth Hormone Deficiency (IGHD) Cohort | Change From Baseline in Height Standard Deviation Score (SDS) at Year 1 | Change at Year 1 | 0.98 standard deviation score | Standard Deviation 0.67 |
| Turner Syndrome (TS) Cohort | Change From Baseline in Height Standard Deviation Score (SDS) at Year 1 | Baseline | -2.17 standard deviation score | Standard Deviation 1.03 |
| Turner Syndrome (TS) Cohort | Change From Baseline in Height Standard Deviation Score (SDS) at Year 1 | Change at Year 1 | 0.71 standard deviation score | Standard Deviation 0.48 |
Primary
Height Velocity Standard Deviation Score (SDS) at Year 1
Height velocity SDS was calculated as height velocity minus reference mean height velocity divided by standard deviation of the reference population. Height velocity SDS reflects the height velocity relative to a reference population of the same age and gender. Height velocity SDS at Year 1 was one of the growth parameter to assess the first year growth response to r-hGH treatment.
Time frame: Year 1
Population: FAS population included all the participants who had provided informed consent and had non-missing height at start (defined as within one month prior to treatment start date) and at 1 year (+/- 120 days) of r-hGH treatment and had pharmacogenomics data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Idiopathic Growth Hormone Deficiency (IGHD) Cohort | Height Velocity Standard Deviation Score (SDS) at Year 1 | 4.18 standard deviation score | Standard Deviation 2.9 |
| Turner Syndrome (TS) Cohort | Height Velocity Standard Deviation Score (SDS) at Year 1 | 2.59 standard deviation score | Standard Deviation 1.92 |
Secondary
Evaluation of the Contribution of Validated Genetic Markers to the Amplitude of First Year Growth Response to r-hGH Therapy in IGHD Children Using Growth Hormone Deficiency Kabi-Pharmacia International Growth Study (GHD KIGS) Predictive Model
GHD KIGS predictive model includes various clinical, auxological and biological markers which are as follows: maximum growth hormone (GH) response to provocation test; age at onset of therapy; birth weight SDS; average GH dose received during the first year of r-hGH therapy; height SDS at start of therapy; the difference between the pre-treatment height SDS of the subject and the mid parental height SDS; and weight SDS at start of therapy.
Time frame: Year 1
Population: No genetic markers were identified during the study therefore, the data for this outcome measure was not analyzed.
Secondary
Evaluation of the Contribution of Validated Genetic Markers to the Amplitude of First Year Growth Response to r-hGH Therapy in TS Girls Using Turner Syndrome Kabi-Pharmacia International Growth Study (TS KIGS) Predictive Model
TS KIGS predictive model includes various clinical, auxological and biological markers which are as follows: maximum GH response to provocation test; age at onset of therapy; birth weight SDS; average GH dose received during the first year of r-hGH therapy; height SDS at start of therapy; the difference between the pre-treatment height SDS of the subject and the mid parental height SDS; and weight SDS at start of therapy.
Time frame: Year 1
Population: No genetic markers were identified during the study therefore, the data for this outcome measure was not analyzed.