E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-associated lipodystrophy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024608 |
E.1.2 | Term | Lipodystrophy |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate a reduction in visceral adipose tissue (VAT) versus placebo. |
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E.2.2 | Secondary objectives of the trial |
1. To demonstrate the efficacy of TH9507 versus placebo in: a. Subject reported outcomes related to body image b. Total cholesterol/ HDL-Cholesterol ratio and triglycerides levels c. IGF-1 levels 2. To characterize the safety profile of TH9507 treatment in HIV subjects with excess abdominal fat accumulation.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects (male or female) aged 18 to 65 inclusive; 2. HIV positive with CD4 cell counts > 100 cells/mm3 and viral load < 10 000 copies/mL within 8 weeks prior to randomization; 3. On stable ART regimen for at least 8 weeks prior to randomization; 4. Have evidence of excess abdominal fat accumulation defined by the following anthropometrics cut off values, considered by the Investigator to be part of the HIV-associated lipodystrophy syndrome and occurring in the context of the treatment of HIV disease: a. For males: Waist circumference greater than or equal to 95 cm and waist/hip ratio greater than or equal to 0.94 b. For females: Waist circumference greater than or equal to 94 cm and waist/hip ratio greater than or equal to 0.88; 5. Female subjects of childbearing potential are eligible only if they are not pregnant (negative pregnancy test) or lactating and they are: a. pre-menopausal and using an acceptable form of birth control prior to study entry and for at least 2 months after completing the treatment, b. or surgically sterilized (tubal ligation or hysterectomy), c. or post-menopausal with no menses for > 1 year; 6. For all female subjects, normal mammography within 6 months of randomization; 7. Have sufficient literacy to read, understand and complete the self-administered patient-reported outcomes questionnaire, as well as all study questionnaires; 8. Signed informed consent before any trial-related activities.
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E.4 | Principal exclusion criteria |
1. Body Mass Index less than or equal to 20 kg/m2; 2. Opportunistic infection or HIV-related disease within 3 months of randomization; 3. History of malignancy of any organ or tissue (with the exception of basal cell carcinoma of the skin, in situ carcinoma of the cervix and stable Kaposi not having required treatment for the past 6 months); 4. For male subjects, suspicion of cancer by prostate examination and PSA > 5 ng/ml at screening; 5. For female subjects, history of breast cancer or proven maternal family history of breast cancer; 6. Hypopituitarism, or history of pituitary tumor/surgery, head irradiation or head trauma that has affected the somatotrophic axis; 7. Untreated hypothyroidism; 8. Co-morbid condition that will not allow the subject to complete the study as per the Investigator’s judgment; 9. Evidence of the following at screening: a. Hepatic dysfunction: ALT or AST greater than or equal to 3 x ULN b. Renal dysfunction: serum creatinine > 133 micromol/L (1.5 mg/dL) c. Anemia: hemoglobin more than 20 g/L below LLN d. Fasting blood glucose greater than or equal to 8.33 mmol/L (150 mg/dL) e. Lipid metabolism dysfunction: fasting triglycerides > 11.3 mmol/L (0.99 g/dL); 10. Uncontrolled hypertension defined as systolic pressure > 140 mmHg and diastolic pressure > 90 mmHg; 11. Use of any hypoglycemic or insulin-sensitizing agent within 6 months of randomization (except subjects previously treated with insulin during pregnancy and where insulin was not required after delivery) and throughout the study; 12. Change in anti-hyperlipemic regimen within 3 months prior to randomization; Use of stable anti-hyperlipemic regimen during the study is not exclusionary; 13. Supraphysiological dose of testosterone [e.g. > 10 mg/day of transdermal testosterone, > 10 g/day of topical/gel testosterone, or > 100 mg/week of IM testosterone (e.g. 200 mg/2 weeks, 300 mg/3 weeks or 400 mg/month), or their equivalent] within 6 months prior to randomization and throughout the study; 14. Change in physiological testosterone regimen within 6 months prior to randomization. Use of stable physiologic testosterone during the study is not exclusionary; 15. Use of anabolic steroids within 6 months prior to randomization and throughout the study; 16. Therapy with estrogen within 2 months prior to randomization and throughout the study; 17. Use of any prescription weight loss agent (anorectics, anorexigenics or anti-obesity agents), appetite stimulant or antianorectic agents within 3 months prior to randomization and throughout the study; 18. Use of any experimental or marketed GH or GRF/GHRH products, GH secretagogues, IGF-1 or IGFBP-3 within 6 months prior to randomization and throughout the study; 19. Prior use of TH9507; 20. Drug or alcohol dependence within 6 months prior to randomization; 21. Use of methadone within 6 months prior to randomization; 22. Participation in a clinical trial with any investigational drug/device within 30 days prior to screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percent change from baseline to week 26 in VAT (Visceral Adipose Tissue) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |