Study of TV-1106 in Growth Hormone-Deficient Adults

Study Overview
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Brief Summary
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The primary objective of this study is to determine the efficacy of 6 months of treatment with TV-1106 compared with placebo on body fat composition.

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Efficacy, Safety and Tolerability Study of TV-1106 in Growth Hormone-Deficient Adults Who Are Not Current Users of rhGH Treatment

Conditions
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Growth Hormone Deficiency

Intervention / Treatment
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* Drug: TV-1106
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion: males and females 18 years of age or over diagnosis of adult growth hormone deficiency (GHD) for at least 6 months, or patients who have hypopituitarism from surgical resection no history of exposure to any rhGH within the past 12 months prior to screening stable, adequate doses of replacement hormones (adrenal, thyroid, estrogen, testosterone, vasopressin) for at least 3 months prior to screening Other criteria apply, please contact the investigator for more information Exclusion: patients with acute or chronic conditions or diseases that could confound results of the study or put the patient at undue risk as determined by the investigator Presence of contraindications to rhGH treatment patients who have participated in another clinical trial with a new chemical/biological entity within 3 months of screening patients with known active malignancy (excluding surgically removed basal cell carcinoma or carcinoma in situ of cervix) patients with a previously treated pituitary tumor with evidence of tumor progression in the past year patients with a new diagnosis of pituitary adenoma or other intracranial tumor within 12 months of screening presence of Prader-Willi syndrome, Turner's syndrome, untreated adrenal insufficiency, active acromegaly in the past 5 years, or active Cushing's syndrome in the past 1 year patients with type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus as indicated by a glycated hemoglobin (HBA1c) of ≥8% patients using weight reducing agents or appetite suppressants women who are pregnant or nursing, or planning pregnancy during the study period Other criteria apply, please contact the investigator for more information

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo was injected subcutaneously once weekly on the same day and time for 24 weeks. To maintain the blind, placebo could be titrated by an unblinded central reader on weeks 4, 8, 12 and 16 to match the effect of dose titration. | Drug: Placebo<br>* Placebo treatment was administered in a blinded fashion and titrated on weeks 4, 8, 12 and 16 to mimic the active treatment.<br>* Other names: Matching placebo;|
| Experimental: TV-1106<br>TV-1106 was injected subcutaneously once weekly on the same day and time for 24 weeks. A common starting dose was 5.0 mg. Doses could be titrated by an unblinded central reader on weeks 4, 8, 12 and 16 until the participant's insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) was within the range of -0.5 to +1.5. | Drug: TV-1106<br>* A starting dose of 5.0 mg was expected to be appropriate for most patients because the daily recommended starting dose of recombinant human growth hormone (rhGH) treatments (e.g. somatropin) is 0.2 mg/day, and the conversion factor was 28. Dosage could be titrated by an unblinded central reader on weeks 4, 8, 12 and 16 until the participant's insulin-like growth factor 1 (IGF-1) standard deviation score (SDS) was within the range of -0.5 to +1.5.<br>* Other names: long-acting growth hormone, albutropin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period | The primary efficacy measure for the study was body fat mass (kg) measured by DXA imaging. The primary outcome as defined in the protocol was the change from baseline to week 24 in body fat mass. Due to the early termination of the study, observed values including endpoint values are reported. Endpoint is the last observed value. | Baseline (Day 1, pre-dose), Week 24, Endpoint in Core period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period | Trunk fat (kg) was assessed based on DXA results. Trunk fat was defined as fat mass - (total arm fat + total leg fat + total head fat). The outcome as defined in the protocol was the within-patient change from baseline to week 24 in trunk fat. Due to the early termination of the study, observed values including endpoint values are reported. Endpoint is the last observed value. | Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period | 
| Insulin-Like Growth Factor 1 Standard Deviation Score (IGF-I SDS) at Baseline, Week 24 and Endpoint in Core Period | IGF-I SDS, as reported by the central laboratory, was a key secondary variable. The week 24 value is a trough value as it was taken 7 days after the last TV-1106 or placebo injection. The outcome as defined in the protocol was the within-patient change from baseline to week 24. Due to the early termination of the study, observed values including endpoint values are reported. Endpoint is the last observed value and is of variable length of time since last TV-1106 or placebo injection. | Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period | 
| Scored Analysis of Quality of Life Assessment of GH Deficiency in Adults (QoL-AGHDA) at Baseline, Week 24 and Endpoint in Core Period | The AGHDA instrument is comprised of 25 questions, with yes or no answers. To each of the 25 questions comprising QOL AGHDA, a score of 1 was assigned if the answer was affirmative and 0 if the answer was negative. Data reported is the total score across the 25 questions for a total range of 0-25 with higher scores representing a poorer quality of life. The outcome as defined in the protocol was the within-patient change from baseline to week 24. Due to the early termination of the study, observed values including endpoint values are reported. Endpoint is the last observed value. | Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period | 
| Participants With Adverse Events During the Core Period | An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents usual activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. | Day 1 up to 24 Weeks | 
| Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Parameters with potentially clinically significant abnormal test results include - Serum chemistry: blood urea nitrogen, creatinine and bilirubin - Hematology: leukocytes, hemoglobin, hematocrit, platelets and neutrophils - Urinalysis: none Significance criteria are listed below with the test. | Day 1 up to 24 Weeks | 
| Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Shifts represented as baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicates an abnormal but not clinically significant finding. Abnormal CS indicates an abnormal and clinically significant finding. | Day 1 up to Week 24 | 
| Thyroid Stimulating Hormone (TSH) at Baseline and Endpoint | One measure of changes in replacement hormones. | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | 
| Free Thyroxin (Free T4) at Baseline and Endpoint | One measure of changes in replacement hormones. | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | 
| Triiodothyronine (Total T3) at Baseline and Endpoint | One measure of changes in replacement hormones. | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | 
| Glycated Hemoglobin (HbA1c) at Baseline and Endpoint | One measure of glucose homeostasis. | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | 
| Fasting Blood Glucose at Baseline and Endpoint | One measure of glucose homeostasis. | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | 
| Insulin at Baseline and Endpoint | One measure of glucose homeostasis. | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | 
| Local Tolerability Assessed by Injection Site Reactions | Participants reporting at least one injection site reaction. | Daay 1 up to Week 24 | 
| Pharmacokinetic Serum Concentration of TV1106 by Nominal Sampling Timepoints | Weeks 4 and 8 serum samples obtained 2 days after TV1106 administration. Weeks 12 and 24 serum samples obtained 7 days after TV1106 administration. Week 16 serum samples obtained 1 day after TV1106 administration. | Baseline (Day 1, pre-dose), Weeks 4, 8, 12, 16, 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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long acting growth hormone