Update on the STEP Study Merck V520 Protocol 023HVTN 502

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Update on the STEP Study Merck V520 Protocol
023/HVTN 502

• Michael N. Robertson, Susan Buchbinder, Dan
  Fitzgerald, Ann Duerr, and Dale Lawrence
• For the STEP Study Protocol Team
• HVTN Meeting
• October 2006

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The STEP Study

• Collaborative study between Merck, HIV Vaccine
  Trials Network (HVTN), and the Division of AIDS
  (DAIDS)/NIH
• aka, Merck Protocol V520-023 and/or HVTN 502
• Phase II Proof-of-Concept study
• Concept Cell-mediated immune (CMI) responses
  elicited by the vaccine will
• Prevent persistent HIV infection and/or
• Control HIV viral replication if infection does
  occur
• www.stepstudies.com

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The STEP StudyProof-of Concept vs. Phase III
study

• Proof-Of-Concept study
• Designed to guide later development
• May use surrogate endpoint
• May use prototype product
• Study population may be limited and focused
• Smaller, cheaper, faster (in general)

• Phase III
• Designed to license product
• Endpoint must be acceptable for registration
• Use final formulation and manufacturing process
• Study population must represent intended use
• Big, expensive, long

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The STEP StudyStudy Population

• HIV-seronegative individuals
• At high risk of HIV infection
• In Clade B geographic regions
• North America, South America, Caribbean,
  Australia
• Encourage enrollment of high risk women and
  diverse racial populations
• Stratified by gender, study site, baseline Ad5
  titer
• Sample size 3000
• Gives adequate power to assess both primary
  efficacy endpoints
• Only infections occurring after Week 12 are
  included in the primary analysis
• Takes into account lower incidence rate in women

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The STEP StudyStudy vaccine

• 11 randomization of placebo active vaccine
• MRKAd5 HIV-1 gag/pol/nef trivalent vaccine
• Placebo contains excipients onlyno vector
• Replication defective due to deletion of E1 gene
• Grown in PER.C6 cells (Crucell)
• 3 doses of 1.5 x 1010 viral genomes as a 1-ml
  intramuscular injection at Day 1, 1 month, and 6
  months post-randomization

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The STEP StudyMRKAd5 HIV-1 Trivalent Vaccine
111 mixture of vectors encoding codon-optomized
gag, pol, and nef sequences from near consensus
clade B strains of HIV-1
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The STEP StudyProjected vs. Actual Enrollment
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The STEP StudyDemographics
Based on preliminary data available as of
30-Sep-2006
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The STEP StudyAd5 titers of screened subjects
Based on preliminary data available as of
30-Sep-2006
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The STEP StudyRetention
Number of participants who have been in study
long enough to reach each visit. Preliminary data
as of 30-Sep-2006
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The STEP StudyAdverse experience (AE) summary

• 76 of study participants have had one or more
  AEs
• Majority are of mild or moderate intensity
• 4 subjects have discontinued from the study due
  to an AE
• 13 have reported a serious AEs
• 3 of which were thought to be at least possibly
  vaccine related
• possible anaphylaxis (reported retrospectively
  weeks after the event)
• diarrhea and dehydration
• severe fever and chills
• 3 study participants have died of non-study
  related cause
• Stab wound during a fight
• Drug overdose
• Gun shot wound

Based on available AE data as of 30-Sep-2006 Data
are blinded, so participants may have received
active vaccine or placebo. Data are preliminary.
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The STEP StudyMost commonly reported AEs
Reported by gt5 of study participants. Based on
available AE data as of 30-Sep-2006. Data are
blinded, so participants may have received active
vaccine or placebo. Data are preliminary.
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The STEP StudyRisk behavior at screening
Randomized volunteers only with available risk
data as of 30-Sep-2006 Behavior in 6 months prior
to screening visit
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The STEP StudyHIV Prevalence at screening

• Males--4.0
• Females--2.7
• Varies from site-to-site depending on
  availability of voluntary counseling and testing
  in the community

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The STEP StudySummary

• It is hard to recruit and retain high risk
  volunteers, but it can be done
• The study vaccine has been generally well
  tolerated
• Study is ongoing

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The STEP Study Protocol Team

• Susan Buchbinder
• Michael Robertson
• Dan Fitzgerald
• Ann Duerr
• Dale Lawrence
• Audrey Mosley
• Missy Shaughnessy
• Colleen Linehan
• Gabriela ONeill
• Joy Ginanni
• Chandra Misra
• Carlette Heath

• Rachael McClennan
• Ellen MacLachlan
• Andrew McKelvey
• Steve Self
• Devan Mehrotra
• David Li
• Sarah Alexander
• Steve Wakefield
• Jen Sarche
• Paula Frew
• Dewayne Mullis

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US Sites
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Sites outside US
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