Growth Hormone Deficiency
Conditions
Keywords
long acting growth hormone
Brief summary
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.
Interventions
DRUGTV-1106
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.
DRUGPlacebo
Placebo treatment was administered in a blinded fashion and titrated on weeks 4, 8, 12 and 16 to mimic the active treatment.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period | Baseline (Day 1, pre-dose), Week 24, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin-Like Growth Factor 1 Standard Deviation Score (IGF-I SDS) at Baseline, Week 24 and Endpoint in Core Period | Baseline (Day 1, pre-dose), Week 24, 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. |
| Scored Analysis of Quality of Life Assessment of GH Deficiency in Adults (QoL-AGHDA) at Baseline, Week 24 and Endpoint in Core Period | Baseline (Day 1, pre-dose), Week 24, 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. |
| Participants With Adverse Events During the Core Period | Day 1 up to 24 Weeks | 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. |
| Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Day 1 up to 24 Weeks | 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. |
| Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Day 1 up to Week 24 | 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. |
| Thyroid Stimulating Hormone (TSH) at Baseline and Endpoint | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | One measure of changes in replacement hormones. |
| Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period | Baseline (Day 1, pre-dose), Week 24, 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. |
| Triiodothyronine (Total T3) at Baseline and Endpoint | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | One measure of changes in replacement hormones. |
| Glycated Hemoglobin (HbA1c) at Baseline and Endpoint | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | One measure of glucose homeostasis. |
| Fasting Blood Glucose at Baseline and Endpoint | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | One measure of glucose homeostasis. |
| Insulin at Baseline and Endpoint | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | One measure of glucose homeostasis. |
| Local Tolerability Assessed by Injection Site Reactions | Daay 1 up to Week 24 | Participants reporting at least one injection site reaction. |
| Pharmacokinetic Serum Concentration of TV1106 by Nominal Sampling Timepoints | Baseline (Day 1, pre-dose), Weeks 4, 8, 12, 16, 24 | 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. |
| Free Thyroxin (Free T4) at Baseline and Endpoint | Baseline (Day 1, pre-dose), Endpoint (up to Week 24) | One measure of changes in replacement hormones. |
Countries
Austria, Czechia, Greece, Hungary, Italy, Russia, United States
Participant flow
Recruitment details
Of the 46 patients screened, 14 patients at 10 centers located in the US and Europe (Austria, Greece, Hungary) met entry criteria and were considered eligible for randomization. Of the 32 patients not randomly assigned to study treatment, 26 were excluded on the basis of inclusion/exclusion criteria and 6 were excluded for other reasons.
Pre-assignment details
Participants were randomly allocated to 1 of 2 treatment groups (TV-1106 or placebo) in a 2:1 allocation to prevent selection bias.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo was injected subcutaneously once weekly on the same day and time for 24 weeks during the Core Period. 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. Participants who completed the Core Period were eligible to enter an open-label extension phase for 12 additional months where all participants received treatment with TV-1106. | 6 |
| TV-1106 TV-1106 was injected subcutaneously once weekly on the same day and time for 24 weeks during the Core Period. 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. Participants who completed the Core Period were eligible to enter an open-label extension phase for 12 additional months where all participants received treatment with TV-1106. | 8 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Core Period (24 Weeks) | Adverse Event | 1 | 0 |
| Core Period (24 Weeks) | Early termination of study by sponsor | 4 | 7 |
| Extension Period (12 Months) | Adverse Event | 1 | 0 |
| Extension Period (12 Months) | Early termination of study by sponsor | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | TV-1106 | Total |
|---|---|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 12.86 | 56.4 years STANDARD_DEVIATION 17.7 | 53.4 years STANDARD_DEVIATION 15.66 |
| Age, Customized <40 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Customized >=40 years | 5 Participants | 7 Participants | 12 Participants |
| Body Mass Index | 26.040 kg/m^2 STANDARD_DEVIATION 6.1675 | 27.716 kg/m^2 STANDARD_DEVIATION 3.3512 | 26.998 kg/m^2 STANDARD_DEVIATION 4.628 |
| Cause of Growth-Hormone Deficiency Idiopathic | 0 Participants | 1 Participants | 1 Participants |
| Cause of Growth-Hormone Deficiency Non-secreting pituitary adenoma | 3 Participants | 2 Participants | 5 Participants |
| Cause of Growth-Hormone Deficiency Other | 3 Participants | 4 Participants | 7 Participants |
| Cause of Growth-Hormone Deficiency Secreting pituitary adenoma | 0 Participants | 1 Participants | 1 Participants |
| Duration of Growth-Hormone Deficiency Diagnosis | 9.270 years STANDARD_DEVIATION 9.312 | 11.104 years STANDARD_DEVIATION 13.1631 | 10.318 years STANDARD_DEVIATION 11.2932 |
| Growth-Hormone Deficiency Onset Adult (>+18 years) | 5 Participants | 7 Participants | 12 Participants |
| Growth-Hormone Deficiency Onset Childhood (<18 years) | 1 Participants | 1 Participants | 2 Participants |
| Height | 175.093 cm STANDARD_DEVIATION 9.1702 | 170.130 cm STANDARD_DEVIATION 8.5363 | 172.257 cm STANDARD_DEVIATION 8.8362 |
| Insulin-like Growth Factor 1 Standard Deviation Score | -2.00 standard deviations STANDARD_DEVIATION 0.978 | -1.40 standard deviations STANDARD_DEVIATION 0.545 | -1.66 standard deviations STANDARD_DEVIATION 0.789 |
| Prior Treatment for Growth-Hormone Deficiency Missing | 4 Participants | 7 Participants | 11 Participants |
| Prior Treatment for Growth-Hormone Deficiency No | 0 Participants | 0 Participants | 0 Participants |
| Prior Treatment for Growth-Hormone Deficiency Yes | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
| Weight | 80.963 kg STANDARD_DEVIATION 24.1867 | 80.448 kg STANDARD_DEVIATION 13.3406 | 80.669 kg STANDARD_DEVIATION 17.9137 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 | 0 / 2 |
| other Total, other adverse events | 3 / 6 | 4 / 8 | 1 / 2 |
| serious Total, serious adverse events | 1 / 6 | 0 / 8 | 0 / 2 |
Outcome results
Primary
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.
Time frame: Baseline (Day 1, pre-dose), Week 24, Endpoint in Core period
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period | Baseline | 24.38 kg | Standard Deviation 7.495 |
| Placebo | Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period | Week 24 | 28.90 kg | — |
| Placebo | Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period | Endpoint | 23.27 kg | Standard Deviation 7.389 |
| TV-1106 | Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period | Baseline | 29.50 kg | Standard Deviation 10.922 |
| TV-1106 | Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period | Week 24 | 31.80 kg | — |
| TV-1106 | Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period | Endpoint | 31.05 kg | Standard Deviation 13.256 |
Secondary
Fasting Blood Glucose at Baseline and Endpoint
One measure of glucose homeostasis.
Time frame: Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Population: Safety population of participants reporting data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Fasting Blood Glucose at Baseline and Endpoint | Baseline | 5.37 MMOL/L | Standard Deviation 2.389 |
| Placebo | Fasting Blood Glucose at Baseline and Endpoint | Endpoint | 4.82 MMOL/L | Standard Deviation 0.818 |
| TV-1106 | Fasting Blood Glucose at Baseline and Endpoint | Baseline | 4.83 MMOL/L | Standard Deviation 0.32 |
| TV-1106 | Fasting Blood Glucose at Baseline and Endpoint | Endpoint | 5.01 MMOL/L | Standard Deviation 0.344 |
Secondary
Free Thyroxin (Free T4) at Baseline and Endpoint
One measure of changes in replacement hormones.
Time frame: Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Population: Safety population of participants reporting data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Free Thyroxin (Free T4) at Baseline and Endpoint | Baseline | 17.22 PMOL/L | Standard Deviation 5.375 |
| Placebo | Free Thyroxin (Free T4) at Baseline and Endpoint | Endpoint | 15.65 PMOL/L | Standard Deviation 2.18 |
| TV-1106 | Free Thyroxin (Free T4) at Baseline and Endpoint | Baseline | 15.26 PMOL/L | Standard Deviation 1.696 |
| TV-1106 | Free Thyroxin (Free T4) at Baseline and Endpoint | Endpoint | 14.54 PMOL/L | Standard Deviation 3.259 |
Secondary
Glycated Hemoglobin (HbA1c) at Baseline and Endpoint
One measure of glucose homeostasis.
Time frame: Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Population: Safety population of participants reporting data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Glycated Hemoglobin (HbA1c) at Baseline and Endpoint | Baseline | 5.53 percentage of total hemoglobin | Standard Deviation 0.647 |
| Placebo | Glycated Hemoglobin (HbA1c) at Baseline and Endpoint | Endpoint | 5.45 percentage of total hemoglobin | Standard Deviation 0.797 |
| TV-1106 | Glycated Hemoglobin (HbA1c) at Baseline and Endpoint | Baseline | 5.49 percentage of total hemoglobin | Standard Deviation 0.422 |
| TV-1106 | Glycated Hemoglobin (HbA1c) at Baseline and Endpoint | Endpoint | 5.51 percentage of total hemoglobin | Standard Deviation 0.358 |
Secondary
Insulin at Baseline and Endpoint
One measure of glucose homeostasis.
Time frame: Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Population: Safety population of participants reporting data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Insulin at Baseline and Endpoint | Endpoint | 65.0 PMOL/L | Standard Deviation 49.68 |
| Placebo | Insulin at Baseline and Endpoint | Baseline | 68.0 PMOL/L | Standard Deviation 68.9 |
| TV-1106 | Insulin at Baseline and Endpoint | Baseline | 57.0 PMOL/L | Standard Deviation 22.68 |
| TV-1106 | Insulin at Baseline and Endpoint | Endpoint | 94.3 PMOL/L | Standard Deviation 89.04 |
Secondary
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.
Time frame: Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Insulin-Like Growth Factor 1 Standard Deviation Score (IGF-I SDS) at Baseline, Week 24 and Endpoint in Core Period | Endpoint | -1.66 standard deviation score | Standard Deviation 0.493 |
| Placebo | Insulin-Like Growth Factor 1 Standard Deviation Score (IGF-I SDS) at Baseline, Week 24 and Endpoint in Core Period | Baseline | -2.00 standard deviation score | Standard Deviation 0.978 |
| Placebo | Insulin-Like Growth Factor 1 Standard Deviation Score (IGF-I SDS) at Baseline, Week 24 and Endpoint in Core Period | Week 24 | -2.00 standard deviation score | — |
| TV-1106 | Insulin-Like Growth Factor 1 Standard Deviation Score (IGF-I SDS) at Baseline, Week 24 and Endpoint in Core Period | Baseline | -1.40 standard deviation score | Standard Deviation 0.545 |
| TV-1106 | Insulin-Like Growth Factor 1 Standard Deviation Score (IGF-I SDS) at Baseline, Week 24 and Endpoint in Core Period | Week 24 | -1.30 standard deviation score | — |
| TV-1106 | Insulin-Like Growth Factor 1 Standard Deviation Score (IGF-I SDS) at Baseline, Week 24 and Endpoint in Core Period | Endpoint | -0.67 standard deviation score | Standard Deviation 0.896 |
Secondary
Local Tolerability Assessed by Injection Site Reactions
Participants reporting at least one injection site reaction.
Time frame: Daay 1 up to Week 24
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Local Tolerability Assessed by Injection Site Reactions | Swelling | 0 Participants |
| Placebo | Local Tolerability Assessed by Injection Site Reactions | Tenderness | 0 Participants |
| Placebo | Local Tolerability Assessed by Injection Site Reactions | Pain | 0 Participants |
| Placebo | Local Tolerability Assessed by Injection Site Reactions | Erythema | 0 Participants |
| Placebo | Local Tolerability Assessed by Injection Site Reactions | Warmth | 0 Participants |
| TV-1106 | Local Tolerability Assessed by Injection Site Reactions | Erythema | 0 Participants |
| TV-1106 | Local Tolerability Assessed by Injection Site Reactions | Warmth | 0 Participants |
| TV-1106 | Local Tolerability Assessed by Injection Site Reactions | Swelling | 0 Participants |
| TV-1106 | Local Tolerability Assessed by Injection Site Reactions | Pain | 2 Participants |
| TV-1106 | Local Tolerability Assessed by Injection Site Reactions | Tenderness | 1 Participants |
Secondary
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.
Time frame: Day 1 up to 24 Weeks
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With Adverse Events During the Core Period | >=1 adverse event | 3 Participants |
| Placebo | Participants With Adverse Events During the Core Period | Severe adverse event | 1 Participants |
| Placebo | Participants With Adverse Events During the Core Period | Treatment-related adverse event | 0 Participants |
| Placebo | Participants With Adverse Events During the Core Period | Other serious adverse events | 1 Participants |
| Placebo | Participants With Adverse Events During the Core Period | Discontinued from study drug due to adverse events | 1 Participants |
| Placebo | Participants With Adverse Events During the Core Period | Deaths | 0 Participants |
| TV-1106 | Participants With Adverse Events During the Core Period | Discontinued from study drug due to adverse events | 0 Participants |
| TV-1106 | Participants With Adverse Events During the Core Period | >=1 adverse event | 4 Participants |
| TV-1106 | Participants With Adverse Events During the Core Period | Other serious adverse events | 0 Participants |
| TV-1106 | Participants With Adverse Events During the Core Period | Severe adverse event | 0 Participants |
| TV-1106 | Participants With Adverse Events During the Core Period | Deaths | 0 Participants |
| TV-1106 | Participants With Adverse Events During the Core Period | Treatment-related adverse event | 2 Participants |
Secondary
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.
Time frame: Day 1 up to 24 Weeks
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Blood urea nitrogen: >=10.71 mmol/L | 0 Participants |
| Placebo | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Creatinine: >=177 mmol/L | 0 Participants |
| Placebo | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Bilirubin: >=34.2 mmol/L | 2 Participants |
| Placebo | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Leukocytes: <=3.0 10^9/L | 1 Participants |
| Placebo | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Hemoglobin: (male) <=115 g/L | 1 Participants |
| Placebo | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Hematocrit: (male) <0.37 L/L | 1 Participants |
| Placebo | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Platelets: <=75 10^9/L | 1 Participants |
| Placebo | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Neutrophils: <=1.0 10^9/L | 1 Participants |
| TV-1106 | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Neutrophils: <=1.0 10^9/L | 0 Participants |
| TV-1106 | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Blood urea nitrogen: >=10.71 mmol/L | 1 Participants |
| TV-1106 | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Hemoglobin: (male) <=115 g/L | 0 Participants |
| TV-1106 | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Creatinine: >=177 mmol/L | 1 Participants |
| TV-1106 | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Platelets: <=75 10^9/L | 0 Participants |
| TV-1106 | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Bilirubin: >=34.2 mmol/L | 0 Participants |
| TV-1106 | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Hematocrit: (male) <0.37 L/L | 0 Participants |
| TV-1106 | Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results | Leukocytes: <=3.0 10^9/L | 0 Participants |
Secondary
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.
Time frame: Baseline (Day 1, pre-dose), Weeks 4, 8, 12, 16, 24
Population: Safety population of participants treated with TV1106
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| TV-1106 | Pharmacokinetic Serum Concentration of TV1106 by Nominal Sampling Timepoints | Week 24, Day 7 | NA ng/mL |
| TV-1106 | Pharmacokinetic Serum Concentration of TV1106 by Nominal Sampling Timepoints | Baseline | NA ng/mL |
| TV-1106 | Pharmacokinetic Serum Concentration of TV1106 by Nominal Sampling Timepoints | Week 4, Day 2 | NA ng/mL |
| TV-1106 | Pharmacokinetic Serum Concentration of TV1106 by Nominal Sampling Timepoints | Week 8, Day 2 | 4.50 ng/mL |
| TV-1106 | Pharmacokinetic Serum Concentration of TV1106 by Nominal Sampling Timepoints | Week 12, Day 7 | NA ng/mL |
| TV-1106 | Pharmacokinetic Serum Concentration of TV1106 by Nominal Sampling Timepoints | Week 16, Day 1 | 9.05 ng/mL |
Secondary
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.
Time frame: Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Scored Analysis of Quality of Life Assessment of GH Deficiency in Adults (QoL-AGHDA) at Baseline, Week 24 and Endpoint in Core Period | Baseline | 3.8 units on a scale | Standard Deviation 5.46 |
| Placebo | Scored Analysis of Quality of Life Assessment of GH Deficiency in Adults (QoL-AGHDA) at Baseline, Week 24 and Endpoint in Core Period | Week 24 | 1.0 units on a scale | — |
| Placebo | Scored Analysis of Quality of Life Assessment of GH Deficiency in Adults (QoL-AGHDA) at Baseline, Week 24 and Endpoint in Core Period | Endpoint | 2.8 units on a scale | Standard Deviation 4.62 |
| TV-1106 | Scored Analysis of Quality of Life Assessment of GH Deficiency in Adults (QoL-AGHDA) at Baseline, Week 24 and Endpoint in Core Period | Baseline | 9.6 units on a scale | Standard Deviation 8.14 |
| TV-1106 | Scored Analysis of Quality of Life Assessment of GH Deficiency in Adults (QoL-AGHDA) at Baseline, Week 24 and Endpoint in Core Period | Week 24 | 0.0 units on a scale | — |
| TV-1106 | Scored Analysis of Quality of Life Assessment of GH Deficiency in Adults (QoL-AGHDA) at Baseline, Week 24 and Endpoint in Core Period | Endpoint | 6.5 units on a scale | Standard Deviation 6.12 |
Secondary
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.
Time frame: Day 1 up to Week 24
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Normal - Normal | 4 Participants |
| Placebo | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Normal - Abnormal CS | 0 Participants |
| Placebo | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Abnormal NCS - Normal | 1 Participants |
| Placebo | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Abnormal NCS - Abnormal NCS | 0 Participants |
| Placebo | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Normal - Abnormal NCS | 1 Participants |
| Placebo | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Abnormal NCS - Abnormal CS | 0 Participants |
| TV-1106 | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Normal - Abnormal NCS | 0 Participants |
| TV-1106 | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Normal - Abnormal CS | 0 Participants |
| TV-1106 | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Normal - Normal | 6 Participants |
| TV-1106 | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Abnormal NCS - Abnormal CS | 0 Participants |
| TV-1106 | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Abnormal NCS - Normal | 1 Participants |
| TV-1106 | Shift From Baseline To Endpoint in Core Period in Electrocardiogram Findings | Abnormal NCS - Abnormal NCS | 1 Participants |
Secondary
Thyroid Stimulating Hormone (TSH) at Baseline and Endpoint
One measure of changes in replacement hormones.
Time frame: Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Population: Safety population of participants reporting data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Thyroid Stimulating Hormone (TSH) at Baseline and Endpoint | Baseline | 0.365 MIU/L | Standard Deviation 0.3791 |
| Placebo | Thyroid Stimulating Hormone (TSH) at Baseline and Endpoint | Endpoint | 0.545 MIU/L | Standard Deviation 0.5439 |
| TV-1106 | Thyroid Stimulating Hormone (TSH) at Baseline and Endpoint | Baseline | 1.028 MIU/L | Standard Deviation 2.0259 |
| TV-1106 | Thyroid Stimulating Hormone (TSH) at Baseline and Endpoint | Endpoint | 0.796 MIU/L | Standard Deviation 1.6971 |
Secondary
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.
Time frame: Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period | Baseline | 12.02 kg | Standard Deviation 4.716 |
| Placebo | Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period | Week 24 | 15.60 kg | — |
| Placebo | Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period | Endpoint | 11.20 kg | Standard Deviation 4.173 |
| TV-1106 | Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period | Baseline | 15.05 kg | Standard Deviation 5.041 |
| TV-1106 | Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period | Week 24 | 12.60 kg | — |
| TV-1106 | Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period | Endpoint | 15.05 kg | Standard Deviation 6.369 |
Secondary
Triiodothyronine (Total T3) at Baseline and Endpoint
One measure of changes in replacement hormones.
Time frame: Baseline (Day 1, pre-dose), Endpoint (up to Week 24)
Population: Safety population of participants reporting data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Triiodothyronine (Total T3) at Baseline and Endpoint | Baseline | 1.80 NMOL/L | Standard Deviation 1.228 |
| Placebo | Triiodothyronine (Total T3) at Baseline and Endpoint | Endpoint | 1.32 NMOL/L | Standard Deviation 0.133 |
| TV-1106 | Triiodothyronine (Total T3) at Baseline and Endpoint | Baseline | 1.71 NMOL/L | Standard Deviation 0.302 |
| TV-1106 | Triiodothyronine (Total T3) at Baseline and Endpoint | Endpoint | 1.64 NMOL/L | Standard Deviation 0.351 |