Assessment of Adherence, Quality of Life, Clinical Response and Safety of Daily and Long-Acting Growth Hormone Therapy

Study Overview
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Brief Summary
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The purpose of the study is to compare quality of life, adherence, insulin resistance, body composition and efficacy of long-acting growth hormone (LAGH) to daily growth hormone (DGH) in children with growth hormone deficiency (GHD). These objectives will be evaluated every 6 months for subjects prior to switch from DGH to LAGH, and 6 months after.

Detailed Description
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Daily subcutaneous injections of recombinant human growth hormone (GH) is the standard of care therapy for children with GH deficiency (GHD). A potential impediment to long-term efficacy of daily GH (DGH) is a lack of adherence and persistence. Multiple Long-Acting Growth Hormone (LAGH) molecules are being developed with the expectation that reduced frequency of injections will improve the patient and caregiver experience leading to improved adherence and, ultimately, improve efficacy. However, the connection between reduced injection frequency, improved adherence and improved efficacy have not yet been demonstrated. GH has metabolic effects that impact insulin resistance, body composition and lipid levels. There is concern that persistently elevated levels of GH provided by LAGH may have a negative effect on metabolism. There is also concern that the larger size of the LAGH molecules in development may limit their access to the target tissues leading to an imbalance of the linear growth and metabolic effects. The purpose of the study is to compare quality of life, adherence, insulin resistance, body composition and efficacy of long-acting growth hormone (LAGH) to daily growth hormone (DGH) in children with growth hormone deficiency (GHD). These objectives will be evaluated every 6 months for subjects prior to switch from DGH to LAGH, and 6 months after.

Official Title
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Assessment of Adherence, Quality of Life, Clinical Response and Safety of Daily and Long-Acting Growth Hormone Therapy

Conditions
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Growth Hormone Deficiency, Growth Hormone Treatment

Intervention / Treatment
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* Drug: Long-Acting Growth Hormone (LAGH)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Girls must be between the ages of 2 and 11 years, and boys must be between the ages of 2 and 13 years Have established diagnosis of pediatric growth hormone deficiency (GHD). For the purposes of the study, GHD is defined as peak growth hormone response to clonidine/arginine stimulation testing of <10 ng/mL Either treatment-naive or currently treated with a daily growth hormone as approved by health insurance Exclusion Criteria: Any medical condition which, in the opinion of the Investigator, can be an independent cause of short stature and/or limit the response to exogenous growth factor treatment Current treatment with long-acting growth hormone Currently pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Transition to long-acting growth hormone (LAGH)<br>Participants in this arm will transition between daily growth hormone treatment and long-acting growth hormone treatment. | Drug: Long-Acting Growth Hormone (LAGH)<br>* Long-acting growth hormone (LAGH) treatment<br>|
| Consistent daily growth hormone (DGH)<br>Participants in this group will continue with daily growth hormone treatment. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insulin Resistance | Fasting glucose and insulin will be measured using standard laboratory tests in order to calculate homeostatic model assessment of insulin resistance (HOMA-IR). The equation is as follows, fasting plasma glucose (mmol/l) multiplied by fasting serum insulin (mU/l) divided by 22.5. HOMA-IR is a unitless measure with no defined range. Higher scores indicate lower insulin sensitivity/higher insulin resistance. Insulin resistance will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years | 
| Change in Bone Mineral Density - DXA | Bone mineral density will be measured using dual energy X-ray absorptiometry (DXA) reported in units of grams per centimeter^2. Bone density will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years | 
| Change in Bone Mineral Density - pQCT | Bone mineral density will be measured using peripheral quantitative computed tomography (pQCT) and reported in units of grams per centimeter^3. Bone density will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years | 
| Change in Percent Fat | Percent fat will be measured using dual energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and BodPod and reported in units of percent kilograms. Percent fat will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years | 
| Change in Fat Free Mass | Fat free mass will be measured using dual energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and BodPod and reported in units of kilograms. Fat free mass will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years | 
| Change in Muscle Content - DXA | Muscle content will be measured using dual energy X-ray absorptiometry (DXA) and BodPod and reported in units of percent kilograms. Muscle content will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years | 
| Change in Muscle Content - pQCT | Muscle content will be measured using peripheral quantitative computed tomography (pQCT) and reported in units of grams per centimeter^3. Muscle content will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PedsQL Questionnaire | The PedsQL Questionnaire contains 23 items rated on a 3- or 5-point Likert scale. Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Total score is calculated as the unweighted average of item scores. Higher scores indicate better health-related quality of life. PedsQL will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years | 
| Change in QOLISSY Questionnaire | The QOLISSY Questionnaire contains 66 items rated on a 5-point Likert scale. Total score is calculated as the mean of item scores. Total scores range from 66 to 330 with higher scores indicating better quality of life. QOLISSY will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years | 
| Change in DID-EQ Questionnaire | The Diabetes Injection Device - Experience Questionnaire (DID-EQ) contains 10 items on a 4-point Likert scale. Total score is calculated as a weighted average of item scores. Total scores range from 10 to 40 with higher score indicating more positive perceptions of injection device characteristics. DID-EQ will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years | 
| Change in DID-PQ Questionnaire | The Diabetes Injection Device - Preference Questionnaire (DID-EQ) contains 10 items on a 5-point Likert scale (-2 to 2), with a total range of -20 to 20. Scores on each end of the scale equal a more positive perception of the device. A higher score indicates a stronger preference for LAGH device and a lower (negative) score indicates a preference for daily growth hormone device. Results will be reported descriptively and categorically as the frequency and percentage of patients reporting each response to each item. DID-EQ will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to | Every six months for approximately 2 years | 
| Change in Adherence Survey | An adherence survey will be administered and medication possession ratio (MPR) data will be obtained. Likert scale items will be measured with a range of 26 to 121, with a higher score indicating a greater burden to growth hormone treatment. Non-Likert scale items (2 items with percent report and 2 items with Yes/No responses) will not be added to a total score but will be reported descriptively. Adherence will be assessed at baseline, 6 months prior to beginning LAGH treatment, and 6 months following the start of LAGH treatment, or every 6 months for two years for those who do not switch to LAGH. Change in values will be reported, for participants on Daily Growth Hormone who never switch to LAGH, from baseline to values obtained at 6 months, 12 months, 18 months, and 24 months. For participants who switch to LAGH, baseline values pre-LAGH treatment will be compared to those obtained 6 months following the start of LAGH treatment. | Every six months for approximately 2 years |