succinylated human serum albumin (suc-hsa) for hiv-1 infection

Conditions: HIV Infections

Summary: the primary objective of the study is to evaluate the pharmacokinetic behavior of suc-hsa after consecutive daily intravenous (i.v.) doses. the secondary objectives are to evaluate the safety and tolerability and the antiretroviral and immunological effects of consecutive daily i.v. doses of suc-hsa.

this is a single centre, single arm study. subjects will receive 5 consecutive daily doses of suc-hsa at a dose of 10 mg/kg on days 0, 1, 2, 3 and 4 on the special investigation unit (siu), with a safety follow up on the siu for 4 hours on day 1 and 2 hours on the next days. there will be follow-up visits on week 1, 2, 4 and 12. standard safety parameters (physical examination, clinical symptoms, laboratory hematology and biochemistry) will be followed until week 12. plasma hiv-1 rna and cd4+/cd8+ cell counts will be assessed at every visit. plasma drug levels (trough and peak) will be measured from baseline until week 2. 6 patients will be included in this study as described in this protocol amendment. eligible subjects are chronic hiv-1 infected patients who have never been treated with antiretroviral treatment and for whom there is no need to start antiretroviral treatment. test product: suc-hsa, a candidate hiv-1 fusion inhibitor. duration of treatment: 5 days criteria for evaluation: * safety: symptoms, signs at physical examination, standard hematology and chemistry laboratory parameters- efficacy: changes in plasma hiv-1 rna and cd4+ t cell count * pharmacokinetics: plasma levels of suc-hsa: cmin, cmax and auc

Eligibility criteria:
inclusion criteria: 1. patient is ≥ 18 years of age; 2. voluntarily signed informed consent; 3. patient has a proven hiv-1 infection (with positive antibodies against hiv-1 and a detectable plasma hiv-1 rna); 4. patient is hiv-1 treatment naïve; 5. cd4+ t-cell count ≥ 350 x 10\^6/l; 6. plasma hiv-1 rna level at screening visit of at least 5.000 copies/ml, and not varying more than ± 0.5 log10 copies during the preceding 6 month period; 7. patient was participant in part 1 of the original suc-hsa study (protocol no. 2003-002, version 2.4, dated 18 november 2003) and the administration of suc-hsa occurred more than 8 weeks ago, or patient was not participant in this study; 8. patient is one of the following: * not heterosexually active, or * a heterosexually active female, agreeing to use an effective method of contraception with her partner (combined oral contraceptive pill; injectable contraceptive; intrauterine contraceptive device (iucd); consistent use of condoms if using these; physiological or anatomical sterility in herself or her partner) from 14 days prior to the first administration of study medication until 4 months after the last, and willing to undergo urine pregnancy tests prior to the first and last administration, or * a heterosexually active male, agreeing to use an effective method of contraception with his partner from the day of the first administration until 4 months after the last administration. exclusion criteria: 1. history of an aids defining event; 2. use of antiretroviral or immunomodulatory therapy; 3. any reason to start antiretroviral therapy at the time of enrolment or which is expected to occur during the course of the study at the time of enrolment; 4. presence of active, replicating hepatitis b and/or c virus co-infection; 5. asat and/or alat \> 3 times upper limit of normal (uln) (aids clinical trials group \[actg\] toxicity scale); 6. serum creatinine measuring \> 1.5 x uln; 7. total bilirubin \> 2x uln; 8. neutropenia (absolute neutrophil count \< 1000/mm3); 9. presence of any clinically significant disease or findings during screening, that in the opinion of the investigator could compromise the safety of the subject; 10. patient is female and (willing to become) pregnant or breast-feeding; 11. any other condition which, in the opinion of the investigator, may interfere with the evaluation of the study objectives.

Keywords: hiv-1 succinylated human serum albumin treatment naive