Phase 2 of new ARVs

Fostemsavir, prodrug of temsavir
(attachment inhibitor)

AI438011 Study : Fostemsavir Phase II
Original article : Lalezari J. Lancet HIV 2015; 2:e427-37 ; Thompson M, CROI 2015, Abs. 545
Last update : 12/10/2015

Dr Anton Pozniak
Chelsea and Westminster Hospital
London, UK

  • Virologic response rates (mITT and observed) and immunologic responses were similar across the fostemsavir and ATV/r arms through Week 48
  • All fostemsavir doses were generally well tolerated with no dose-response safety signals reported
  • Continuation dose of fostemsavir 1200 mg QD for the Phase IIb study
  • Phase III study in heavily treatment-experienced patients with limited therapeutic options
    • Phase III dose : 600 mg BID
    • Subjects enrolled regardless of baseline susceptibility to temsavir
    • A retrospective analysis will be conducted to determine whether a baseline phenotypic assay is necessary in the future

Design :

  • Phase IIb , randomised, active-controlled, bl inded -to-fostemsavir dose
  • ARV-experienced patients, > 18 years, HIV RNA > 1,000 c/ mL , CD4 cell count > 50/mm3
  • Susceptibility to RAL, TDF and ATV
  • Temsavir IC 50 < 0.1 μM (100 nM ) by screening Phenosense ® entry assay

Objective :

  • Primary endpoints (W24) :
    • % HIV-1 RNA < 50 c/ mL
    • % of SAEs and AEs leading to discontinuation
  • Secondary endpoints (W48) :
    • %HIV-1 RNA < 50 c/ mL
    • Change in CD4 T- cell count from baseline
    • % SAEs and AEs leading to discontinuation

Baseline characteristics and patient disposition

Fostemsavir 7 days of monotherapy
Mean change in HIV RNA from baseline (log 10 c/ml)

HIV RNA < 50 c/ mL or < 400 c/ mL at W24

HIV RNA < 50 c/ml at W24 by baseline HIV RNA (observed )

HIV RNA < 50 c/ mL or < 400 c/ mL at W48, mITT snapshot

HIV RNA < 50 c/ mL at W48, observed

Safety data through W48


* Anal abscess, herpes encephalitis, overdose (3), extrapulmonary tuberculosis (2), herpes zoster , abdominal pain, myalgia , spontaneous abortion, acute renal failure , cellulitis (2), lymphangitis , chronic cholecystitis , back pain, pneumonia , pyelonephritis , diarrhea , cholelithiasis , migraine
** Illegal substance use, extrapulmonary tuberculosis (3), acute renal failure , abdominal distension, flatulence, nausea , jaundice ; 6/7 AE leading to discontinuation in first 24 weeks

Grade 3-4 laboratory abnormalities (≥ 2 subjects )

Mean change from baseline at W48 in fasting lipids , mg/ dL

   

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