Lipodystrophy, HIV Infections
Conditions
Keywords
HIV, Lipodystrophy, Abdominal fat accumulation, Growth hormone releasing hormone, HIV-associated lipodystrophy, Treatment experienced
Brief summary
Assessing the Efficacy and Long-Term Safety of a 2 mg dose of TH9507, a Growth Hormone-Releasing Factor Analog, in HIV Subjects with Excess Abdominal Fat Accumulation
Detailed description
HIV lipodystrophy affects a significant proportion of patients treated with combination antiretroviral therapy (ART) and is characterized by excess visceral fat accumulation, loss of extremity and subcutaneous fat, in association with dyslipidemia and insulin resistance. Data from the first Phase 3 multicenter, randomized, placebo-controlled trial demonstrated that daily administration of 2mg TH9507, a growth hormone releasing factor (GRF), to HIV- infected patients with excess of abdominal fat accumulation for 26 weeks resulted in decreases in visceral adipose tissue (VAT) and trunk fat, with lesser changes in limb fat and subcutaneous adipose tissue (SAT). The present study is aimed at confirming the observations made during the first Phase 3 study.
Interventions
DRUGTesamorelin
DRUGPlacebo for Tesamorelin
Sponsors
Theratechnologies
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who have completed the 26 weeks treatment period of the TH9507-CTR-1011 study. * Signed informed consent before any trial-related activities.
Exclusion criteria
* Fasting blood glucose \>8.33 mmoL (150 mg/dL) at the end of the TH9507-CTR-1011 study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in Fasting Blood Glucose at Week 52 | Baseline and Week 52 | Blood glucose was determined after an overnight fast. Changes in blood glucose between baseline and Week 52 are reported. |
| Changes From Baseline in 2 h Oral Glucose Tolerance Test (OGTT) at Week 52 | Baseline and Week 52 | Glucose tolerance was determined after an overnight fast using standard 75 gram-oral glucose tolerance test (OGTT) with glucose measured at timepoints 0, 30, 60, 90 and 120. Changes in glucose tolerance between baseline and Week 52 are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in Visceral Adipose Tissue (VAT) at Week 52 | Baseline and Week 52 | Visceral adipose tissue (VAT) was assessed by computerized tomography (CT) scan using a single-slice. Changes in VAT between baseline and Week 52 are reported. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline in Triglycerides at Week 52 | Baseline and Week 52 | Blood lipid levels were determined under fasting conditions. Changes in triglycerides between baseline and Week 52 are reported. |
| Changes From Baseline in Total Cholesterol/HDL Cholesterol Ratio at Week 52 | Baseline and Week 52 | Blood lipid levels were determined under fasting conditions. Total Cholesterol/HDL Cholesterol Ratio was obtained by dividing the total cholesterol value by the value of the HDL cholesterol. Changes between baseline and Week 52 are reported. |
Countries
Belgium, Canada, France, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tesamorelin 52 Weeks Tesamorelin 2 mg/day for 52 weeks | 92 |
| Tesamorelin (26 Weeks) - Placebo (26 Weeks) Tesamorelin 2 mg/day for 26 weeks followed by Placebo for 26 weeks | 85 |
| Placebo (26 Weeks) - Tesamorelin (26 Weeks) Placebo for 26 weeks followed by Tesamorelin 2 mg/day for 26 weeks | 86 |
| Total | 263 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 | 5 |
| Overall Study | Lost to Follow-up | 2 | 2 | 1 |
| Overall Study | Protocol Violation | 1 | 3 | 1 |
| Overall Study | Unknown reason | 0 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 10 | 7 |
Baseline characteristics
| Characteristic | Tesamorelin 52 Weeks | Tesamorelin (26 Weeks) - Placebo (26 Weeks) | Placebo (26 Weeks) - Tesamorelin (26 Weeks) | Total |
|---|---|---|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 6.9 | 48.9 years STANDARD_DEVIATION 7.2 | 48.4 years STANDARD_DEVIATION 7.9 | 48.3 years STANDARD_DEVIATION 7.3 |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 11 Participants | 29 Participants |
| Sex: Female, Male Male | 83 Participants | 76 Participants | 75 Participants | 234 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 92 | 11 / 85 | 28 / 86 |
| serious Total, serious adverse events | 3 / 92 | 1 / 85 | 3 / 86 |
Outcome results
Primary
Changes From Baseline in 2 h Oral Glucose Tolerance Test (OGTT) at Week 52
Glucose tolerance was determined after an overnight fast using standard 75 gram-oral glucose tolerance test (OGTT) with glucose measured at timepoints 0, 30, 60, 90 and 120. Changes in glucose tolerance between baseline and Week 52 are reported.
Time frame: Baseline and Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesamorelin 52 Weeks | Changes From Baseline in 2 h Oral Glucose Tolerance Test (OGTT) at Week 52 | -2 mg/dL | Standard Deviation 38 |
| Tesamorelin (26 Weeks) - Placebo (26 Weeks) | Changes From Baseline in 2 h Oral Glucose Tolerance Test (OGTT) at Week 52 | 2 mg/dL | Standard Deviation 35 |
| Placebo (26 Weeks) - Tesamorelin (26 Weeks) | Changes From Baseline in 2 h Oral Glucose Tolerance Test (OGTT) at Week 52 | 7 mg/dL | Standard Deviation 37 |
p-value: >0.05ANCOVA
Primary
Changes From Baseline in Fasting Blood Glucose at Week 52
Blood glucose was determined after an overnight fast. Changes in blood glucose between baseline and Week 52 are reported.
Time frame: Baseline and Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesamorelin 52 Weeks | Changes From Baseline in Fasting Blood Glucose at Week 52 | 0 mg/dL | Standard Deviation 16 |
| Tesamorelin (26 Weeks) - Placebo (26 Weeks) | Changes From Baseline in Fasting Blood Glucose at Week 52 | -2 mg/dL | Standard Deviation 34 |
| Placebo (26 Weeks) - Tesamorelin (26 Weeks) | Changes From Baseline in Fasting Blood Glucose at Week 52 | 1 mg/dL | Standard Deviation 21 |
p-value: >0.05ANCOVA
Secondary
Changes From Baseline in Visceral Adipose Tissue (VAT) at Week 52
Visceral adipose tissue (VAT) was assessed by computerized tomography (CT) scan using a single-slice. Changes in VAT between baseline and Week 52 are reported.
Time frame: Baseline and Week 52
Population: All data were included in the analysis by intention to treat principles. Intent to treat populations were defined as all randomized subjects who were exposed to study drug (i.e injection of at least 1 dose of study drug).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesamorelin 52 Weeks | Changes From Baseline in Visceral Adipose Tissue (VAT) at Week 52 | -41 cm^2 | Standard Deviation 57 |
| Tesamorelin (26 Weeks) - Placebo (26 Weeks) | Changes From Baseline in Visceral Adipose Tissue (VAT) at Week 52 | 0 cm^2 | Standard Deviation 53 |
| Placebo (26 Weeks) - Tesamorelin (26 Weeks) | Changes From Baseline in Visceral Adipose Tissue (VAT) at Week 52 | -26 cm^2 | Standard Deviation 47 |
p-value: <0.001ANCOVA
Other Pre-specified
Changes From Baseline in Total Cholesterol/HDL Cholesterol Ratio at Week 52
Blood lipid levels were determined under fasting conditions. Total Cholesterol/HDL Cholesterol Ratio was obtained by dividing the total cholesterol value by the value of the HDL cholesterol. Changes between baseline and Week 52 are reported.
Time frame: Baseline and Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesamorelin 52 Weeks | Changes From Baseline in Total Cholesterol/HDL Cholesterol Ratio at Week 52 | -0.23 ratio | Standard Deviation 1.75 |
| Tesamorelin (26 Weeks) - Placebo (26 Weeks) | Changes From Baseline in Total Cholesterol/HDL Cholesterol Ratio at Week 52 | 0.13 ratio | Standard Deviation 1.19 |
| Placebo (26 Weeks) - Tesamorelin (26 Weeks) | Changes From Baseline in Total Cholesterol/HDL Cholesterol Ratio at Week 52 | 0.06 ratio | Standard Deviation 1.01 |
p-value: >0.05ANCOVA
Other Pre-specified
Changes From Baseline in Triglycerides at Week 52
Blood lipid levels were determined under fasting conditions. Changes in triglycerides between baseline and Week 52 are reported.
Time frame: Baseline and Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tesamorelin 52 Weeks | Changes From Baseline in Triglycerides at Week 52 | -37 mg/dL | Standard Deviation 196 |
| Tesamorelin (26 Weeks) - Placebo (26 Weeks) | Changes From Baseline in Triglycerides at Week 52 | 4 mg/dL | Standard Deviation 177 |
| Placebo (26 Weeks) - Tesamorelin (26 Weeks) | Changes From Baseline in Triglycerides at Week 52 | 1 mg/dL | Standard Deviation 120 |
p-value: >0.05ANCOVA