Trial Outcomes & Findings for Study of TV-1106 in Growth Hormone-Deficient Adults (NCT NCT02410343)

Last Updated: 2022-01-24

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

14 participants

Primary outcome timeframe

Baseline (Day 1, pre-dose), Week 24, Endpoint in Core period

Results posted on

2022-01-24

Participant Flow

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.

Participants were randomly allocated to 1 of 2 treatment groups (TV-1106 or placebo) in a 2:1 allocation to prevent selection bias.

Participant milestones

Participant milestones
Measure	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.	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.
Core Period (24 Weeks) STARTED	6	8
Core Period (24 Weeks) COMPLETED	1	1
Core Period (24 Weeks) NOT COMPLETED	5	7
Extension Period (12 Months) STARTED	1	1
Extension Period (12 Months) COMPLETED	0	0
Extension Period (12 Months) NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
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

Study of TV-1106 in Growth Hormone-Deficient Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=6 Participants 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.	TV-1106 n=8 Participants 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.	Total n=14 Participants Total of all reporting groups
Age, Continuous	49.3 years STANDARD_DEVIATION 12.86 • n=5 Participants	56.4 years STANDARD_DEVIATION 17.70 • n=7 Participants	53.4 years STANDARD_DEVIATION 15.66 • n=5 Participants
Age, Customized <40 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Customized >=40 years	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Weight	80.963 kg STANDARD_DEVIATION 24.1867 • n=5 Participants	80.448 kg STANDARD_DEVIATION 13.3406 • n=7 Participants	80.669 kg STANDARD_DEVIATION 17.9137 • n=5 Participants
Height	175.093 cm STANDARD_DEVIATION 9.1702 • n=5 Participants	170.130 cm STANDARD_DEVIATION 8.5363 • n=7 Participants	172.257 cm STANDARD_DEVIATION 8.8362 • n=5 Participants
Body Mass Index	26.040 kg/m^2 STANDARD_DEVIATION 6.1675 • n=5 Participants	27.716 kg/m^2 STANDARD_DEVIATION 3.3512 • n=7 Participants	26.998 kg/m^2 STANDARD_DEVIATION 4.6280 • n=5 Participants
Insulin-like Growth Factor 1 Standard Deviation Score	-2.00 standard deviations STANDARD_DEVIATION 0.978 • n=5 Participants	-1.40 standard deviations STANDARD_DEVIATION 0.545 • n=7 Participants	-1.66 standard deviations STANDARD_DEVIATION 0.789 • n=5 Participants
Duration of Growth-Hormone Deficiency Diagnosis	9.270 years STANDARD_DEVIATION 9.3120 • n=5 Participants	11.104 years STANDARD_DEVIATION 13.1631 • n=7 Participants	10.318 years STANDARD_DEVIATION 11.2932 • n=5 Participants
Growth-Hormone Deficiency Onset Adult (>+18 years)	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Growth-Hormone Deficiency Onset Childhood (<18 years)	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Cause of Growth-Hormone Deficiency Secreting pituitary adenoma	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Cause of Growth-Hormone Deficiency Non-secreting pituitary adenoma	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Cause of Growth-Hormone Deficiency Idiopathic	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Cause of Growth-Hormone Deficiency Other	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Prior Treatment for Growth-Hormone Deficiency Yes	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Prior Treatment for Growth-Hormone Deficiency No	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Prior Treatment for Growth-Hormone Deficiency Missing	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1, pre-dose), Week 24, Endpoint in Core period

Population: ITT

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants 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.	TV-1106 n=8 Participants 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.
Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period Baseline	24.38 kg Standard Deviation 7.495	29.50 kg Standard Deviation 10.922
Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period Week 24	28.90 kg Standard Deviation NA Value from a single individual	31.80 kg Standard Deviation NA Value from a single individual
Body Fat Mass at Baseline, Week 24 and Endpoint in Core Period Endpoint	23.27 kg Standard Deviation 7.389	31.05 kg Standard Deviation 13.256

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period

Population: ITT

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.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants 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.	TV-1106 n=8 Participants 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.
Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period Baseline	12.02 kg Standard Deviation 4.716	15.05 kg Standard Deviation 5.041
Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period Week 24	15.60 kg Standard Deviation NA Value from a single individual	12.60 kg Standard Deviation NA Value from a single individual
Total Trunk Fat at Baseline, Week 24 and Endpoint in Core Period Endpoint	11.20 kg Standard Deviation 4.173	15.05 kg Standard Deviation 6.369

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period

Population: ITT

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.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants 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.	TV-1106 n=8 Participants 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.
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	-1.40 standard deviation score Standard Deviation 0.545
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 Standard Deviation NA Value from a single individual	-1.30 standard deviation score Standard Deviation NA Value from a single individual
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	-0.67 standard deviation score Standard Deviation 0.896

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-dose), Week 24, Endpoint in Core Period

Population: ITT

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.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants 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.	TV-1106 n=8 Participants 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.
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	9.6 units on a scale Standard Deviation 8.14
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 Standard Deviation NA Value from a single individual	0.0 units on a scale Standard Deviation NA Value from a single individual
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	6.5 units on a scale Standard Deviation 6.12

SECONDARY outcome

Timeframe: Day 1 up to 24 Weeks

Population: Safety population

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.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants 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.	TV-1106 n=8 Participants 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.
Participants With Adverse Events During the Core Period >=1 adverse event	3 Participants	4 Participants
Participants With Adverse Events During the Core Period Severe adverse event	1 Participants	0 Participants
Participants With Adverse Events During the Core Period Treatment-related adverse event	0 Participants	2 Participants
Participants With Adverse Events During the Core Period Deaths	0 Participants	0 Participants
Participants With Adverse Events During the Core Period Other serious adverse events	1 Participants	0 Participants
Participants With Adverse Events During the Core Period Discontinued from study drug due to adverse events	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 up to 24 Weeks

Population: Safety population

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.

Outcome measures

Outcome measures
Measure	Placebo n=6 Participants 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.	TV-1106 n=8 Participants 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.
Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results Blood urea nitrogen: >=10.71 mmol/L	0 Participants	1 Participants
Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results Creatinine: >=177 mmol/L	0 Participants	1 Participants
Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results Bilirubin: >=34.2 mmol/L	2 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results Leukocytes: <=3.0 10^9/L	1 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results Hemoglobin: (male) <=115 g/L	1 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results Hematocrit: (male) <0.37 L/L	1 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results Platelets: <=75 10^9/L	1 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Blood and Urine Test Results Neutrophils: <=1.0 10^9/L	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 up to Week 24

Population: Safety population

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.