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Motivate 1 Study: Efficacy and Safety of Maraviroc plus Optimized Background Therapy In Viremic, ART-Experienced Patients Infected With CCR5-Tropic HIV-1: 24-Week Results of Phase 2b/3 Studies
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Reported by Jules Levin
CROI Feb 27, 2007, Los Angeles
Brief Summary:
In Motivate 1 study which took place in the USA & Canada patients were randomized to maraviroc once or twice daily plus OBT (optimized background therapy) or placebo plus OBT:....Viral load reduction at week 24 was -1.82 log for patients on MVC QD+OBT (N=232), -1.95 log for patients on MVCBID+OBT (n=235), and -1.03 for patients on placebo+OBT (n=118)..... 60.4% <400 c/ml for patients on MVC BID +OBT (p<0.0001 versus placebo + OBT), 54.7% <400 c/ml for patients on MVC QD +OBT (p<0.0001 versus placebo + OBT), 31.4% <400 c/ml on placebo+OBT..... CD4 increase was 110 on MVC & 52 on placebo....you can see safety profile below in the tables but there is no indication from the data for safety concerns; and the adverse events reported below appear normal.
Motivate 2 is the other international study and IÕll present the results in the report.
Presentation No. 104bLB
MOTIVATE 1
USA and Canada
Efficacy and Safety of Maraviroc plus Optimized Background Therapy In Viremic, ART-Experienced Patients Infected With CCR5-Tropic HIV-1: 24-Week Results of Phase 2b/3 Studies J Lalezari1, J Goodrich2, E DeJesus3,
H Lampiris4, R Gulick5, M Saag6,
C Ridgway7, M McHale7, E van der Ryst7,
and H Mayer2
on behalf of the MOTIVATE 1 Study Group
1Quest Clinical Research, UCSF, San Francisco, CA, USA; 2Pfizer Global Research and Development, New London, CT, USA; 3Orlando Immunology Center, Orlando, FL, USA; 4San Francisco Veterans Affairs Medical Center, UCSF,
San Francisco, CA, USA; 5Weill Medical College of Cornell University, New York, NY, USA; 6University of Alabama at Birmingham, Birmingham, AL, USA; 7Pfizer Global Research and Development, Sandwich, UK
Presentation No. 104aLB
MOTIVATE 2
Europe, Australia and USA
M Nelson1, G Ftkenheuer2, I Konourina3,
A Lazzarin4, N Clumeck5, A Horban6,
M Tawadrous7, J Sullivan3, H Mayer7,
and E van der Ryst3
on behalf of the MOTIVATE 2 Study Group
1Chelsea & Westminster Hospital, London, UK; 2Universitaetsklinik Koln, Koln, Germany; 3Pfizer Global Research and Development, Sandwich, UK; 4IRCCS San Raffaele, Milan, Italy; 5C.H.U. St-Pierre, Brussels, Belgium; 6Szpital Zakazny Centrum Diagnostyki i Terapii AIDS, Warsaw, Poland; 7Pfizer Global Research and Development, New London, CT, USA
BACKGROUND
Oral CCR5 antagonist
Potent antiviral activity in vitro and in vivo against CCR5-tropic (R5)
HIV-1 including multi-drug-resistant HIV-1, but not CXCR4-tropic (X4)
or dual/mixed-tropic (D/M) HIV-1:
-- Generally well tolerated in healthy volunteers and patients in Phase 1/2a clinical trials
-- Maximum HIV-1 RNA reductions of > 1 log10 copies/mL in patients with R5 HIV-1 treated with maraviroc monotherapy at ³ 100 mg BID
MOTIVATE 1 and 2: Ongoing Phase 2b/3 trials assessing the safety and efficacy of maraviroc in ARV-experienced patients
-- Primary endpoint at 24 weeks: Mean change from baseline in HIV-1 RNA
Trial Design
601 patients in Moticate 1 and 475 patients in Motivate 2 were randomized 1:2:2 to
OBT+placebo
OBT+ Maraviroc (150 mg once daily, QD)
or
OBT+Maraviroc (150 mg BID, twice daily)
* OBT = optimized background therapy of 3Š6 ARVs (PK boosting doses of RTV not counted as an ARV)
Patients receiving a PI (except TPV) and/or delavirdine in their OBT received 150 mg dose of MVC,
all other patients received 300 mg dose of MVC
![placebo-1.gif](../images/030507/placebo-1.gif)
MOTIVATE 1 (North America):
24 Week Results
Demographics and Baseline Characteristics
Includes all patients who received at least one dose of study medication
Median Cd4 was 150-168
Median HIV-1 RNA was 4.85 log
43% had Fuzeon in regimen
66-72% had 2 or less active drugs in OBT
![MVC-2.gif](../images/030507/MVC-2.gif)
Mean Change in HIV-1 RNA from Baseline at Week 24
Includes all patients who received at least one dose of study medication
Viral load reduction at week 24 was -1.82 log for patients on MVC QD+OBT (N=232), -1.95 log for patients on MVCBID+OBT (n=235), and -1.03 for patients on placebo+OBT (n=118).
![MCVqD-3.gif](../images/030507/MCVqD-3.gif)
Percentage of Patients with Undetectable HIV-1 RNA
-- 60.4% <400 c/ml for patients on MVC BID +OBT (p<0.0001 versus placebo + OBT)
-- 54.7% <400 c/ml for patients on MVC QD +OBT (p<0.0001 versus placebo + OBT)
-- 31.4% <400 c/ml on placebo+OBT
![timeWeeks-4.gif](../images/030507/timeWeeks-4.gif)
Mean Change in CD4 Count from Baseline to Week 24
CD4 increase was 110 on MVC & 52 on placebo.
![BID-5.gif](../images/030507/BID-5.gif)
Mean Change in HIV-1 RNA from Baseline at Week 24
According to Screening HIV-1 RNA and Enfuvirtide Use in OBT*
Regardless of whether viral load was <100,000> viral load reductions were similar: patients with <100,000 at baseline-- -2.02 log on MVC QD, -2.10 log on MVC BID, -1.45 log on placebo; there was little difference in viral load reduction whether patients were on Fuzeon or not. However, for patients receiving MVC+Fuzeon viral load reduction was -2.08 vs -1.31 for patients on placebo+OBT without Fuzeon. Of note the patients in the table below who received Fuzeon included patients both who were nave & not nave to Fuzeon. However, in speaking with Pfizer if you look at Fuzeon nave patients the same no difference was seen.
![LOCF-6.gif](../images/030507/LOCF-6.gif)
![INci-1.gif](../images/030507/INci-1.gif)
![max-2.gif](../images/030507/max-2.gif)
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