TH9507 in Patients With HIV-Associated Lipodystrophy

A Phase 3 Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Assessing the Efficacy and Safety of a 2 mg Dose of TH9507, a Growth Hormone Releasing Factor Analog, in HIV Patients With Excess of Abdominal Fat Accumulation

HIV lipodystrophy affects a significant proportion of patients treated with combination antiretroviral therapy (ART) and is characterized by excess visceral fat accumulation and loss of extremity and subcutaneous fat, in association with dyslipidemia and insulin resistance. Data from a previous randomized, placebo-controlled trial demonstrated that daily administration of 2mg TH9507, a growth hormone releasing factor (GRF), to HIV patients with an excess of abdominal fat accumulation for 12 weeks resulted in decreases in visceral adipose tissue (VAT) and trunk fat, with no significant changes in limb fat and subcutaneous adipose tissue (SAT). This study is aimed at further assessing the efficacy and safety of 2 mg TH9507 in a larger population of HIV patients treated with ART and experiencing an excess of abdominal fat accumulation.

Inclusion Criteria:

• Ages 18 to 65 years inclusive

• HIV positive; CD4 cell counts >100 cells/mm3; viral load <10,000 copies/mL (stable for 8 weeks)

• On stable ART regimen for at least 8 weeks prior to randomization

• Have evidence of abdominal fat accumulation defined by the following anthropometric cut off values:

  • For males: waist circumference > 95 cm and waist to hip ratio > 0.94;
  • For females: waist circumference > 94 cm and waist to hip ratio > 0.88.

• Females of childbearing potential not pregnant or lactating; normal mammography within 6 months of study.

• Signed informed consent

Exclusion Criteria:

• Body mass index < 20 kg/m2
• Opportunistic infection; HIV-related disease within 3 months of study.
• History of malignancy; active neoplasm.
• Prostate-specific antigen (PSA) >5 ng/mL at screening
• Hypopituitarism; history of pituitary tumor/surgery; head irradiation; head trauma that has affected the somatotropic axis.
• Untreated hypothyroidism
• Type 1 diabetics and type 2 diabetics on oral hypoglycemic or insulin sensitizing agent within 6 months of study
• ALT or AST > 3 x ULN; serum creatinine > 133 mmol/L (1.5 mg/dL); hemoglobin more than 20 g/L below LLN; fasting blood glucose > 8.33 mmol/L (150 mg/dL); fasting triglycerides > 11.3 mmol/L (0.99 g/dL).
• Untreated hypertension
• Change in anti-hyperlipemic regimen within 3 months prior to study
• Change in testosterone regimen and/or supraphysiological dose of testosterone
• Estrogen therapy
• Anoretics/anorexigenics or anti-obesity agents within 3 months of study
• Growth hormone (GH); GH secretagogues; growth hormone releasing factor (GRF) products; IGF-1; or IGFBP-3 within 6 months of study.
• Drug or alcohol dependence or use of methadone within 6 months of study entry
• Participation in a clinical trial with any investigational drug/device within 30 days of screening.