Presentation Abstract

Session: 97-New Antiretrovirals
Monday, Sep 13, 2010, 11:15 AM - 1:15 PM
Presentation Title: H-933 - A Phase-Ib/IIa Dose-Escalation Study of OBP-601 (4’-ethynyl-d4T, Festinavir) in Treatment-Experienced, HIV-1-Infected Patients
Location: Exhibit Hall B1
Poster Board Number: 396
Presentation Number: H-933
Pres. Time: Monday, Sep 13, 2010, 11:15 AM - 1:15 PM
Category: F1
Keywords: nucleos(t)ide reverse transcriptase inhibitors ; HIV therapy ; Phase-1 
Author(s): L. COTTE1, P. DELLAMONICA 2, F. RAFFI 3, Y. YAZDANPANAH 4, J. M. MOLINA 5, F. BOUE 6, Y. URATA 7;
1Hospices Civils de Lyon, Lyon, France, 2Université de Nice, Nice, France, 3Hotel-Dieu, Nantes, France, 4Ctr. Hosp.ier de Tourcoing, Tourcoing, France, 5Hosp. Saint Louis, Paris, France, 6Hosp. Antoine Beclère, Paris, France, 7ONCOLYS Biopharma, Tokyo, Japan.
Financial Disclosures:  L. Cotte, None..
P. Dellamonica, None..
F. Raffi, None..
Y. Yazdanpanah, None..
J. M. Molina, None..
F. Boue, None. 
Y. Urata,
ONCOLYS Biopharma Role(s): Other, President and CEO, Received: Salary, Other Financial Benefit.
Abstract: Background: OBP-601 is a novel NRTI with in vitro activity against several wild type and drug-resistant HIV-1 and prolonged activity after drug removal. OBP-601 is a weak inhibitor of mitochondrial DNA synthesis. OBP-601 was found to be safe and well-tolerated up to 900 mg in single oral administration in healthy volunteers in a phase-Ia clinical study. Methods: A double-blind, placebo-controlled, dose escalating study was undertaken in treatment-experienced, currently off-treatment, HIV-1-infected patients. Four cohorts of 8 patients were sequentially recruited, to receive OBP-601 monotherapy 100, 200, 300 and 600 mg QD for 10 days (6 patients/cohort) or placebo (2 patients/cohort). A 24h pharmacokinetic was done on day 1 and day 10. Safety, tolerability, HIV-RNA viral load and CD4 counts were assessed at baseline and at each visits. RT and protease genotyping were performed at baseline, day 10 and day 17. Results: A total of 27 patients reported 99 AEs from which 62 where considered unrelated to OBP-601. No clear pattern of AEs was observed. The maximum tolerated dose was not reached. A dose-dependent correlation between AUC and dosage was observed. No new RT mutation emerged at day 10 and 17.
Placebo
(n=8)		100 mg
(n=6)		200 mg
(n=6)		300 mg
(n=6)		600 mg
(n=6)
Baseline mean CD4 (/mm3)400358334465476
Baseline mean HIV-RNA (log copies/ml)4.174.364.624.474.23
Patients with AEs (n)44251
Nb of grade 2/3 AEs (all (unrelated))1 (0)5 (0)3 (2)0 (0)4 (3)
Nb of grade 4 AEs (all (unrelated))0 (0)0 (0)0 (0)0 (0)2 (2)
AUC day 1 / day 10 (h*ng/ml)-6382 / 676512642 / 1352017475 / 1955839645 / 42695
Δ HIV-RNA from baseline (log copies/ml)-0.07-0.87-0.98-1.36-1.22

Conclusions: OBP-601 monotherapy for 10 days appears safe and well-tolerated up to 600 mg/day in HIV-infected, treatment-experienced patients. Antiviral efficacy appears remarkable for a nucleoside and deserves further studies.



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