The International Maternal Pediatric Adolescent AIDS Clinical Trials Network

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The International Maternal Pediatric Adolescent
AIDS Clinical Trials Network
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Four Scientific Committees

• Primary Therapy
• Complications
• Prevention of Mother to Child Transmission
  (PMTCT)
• Vaccine/IBT

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Four Scientific Committees

• Conceive and develop protocols
• Implement research strategies
• Monitor protocol development and implementation
• Each scientific committee will have up to 12
  voting members
• Members will come from both domestic and
  international sites

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Primary Therapy

• Specific Aim 1 To evaluate the pharmacokinetics
  and safety of new ARVs and new ARV formulations
  leading to optimal labeling and licensing for
  HIV-infected infants, children, and adolescents.
• Specific Aim 2 Explore new treatment strategies
  for antiretroviral therapy of HIV-1 infected
  infants, children, and adolescents that provide
  new insights useful in the development of
  treatment guidelines.
• Specific Aim 3 Use antiretroviral agents and
  immune-based-therapies to investigate HIV-1
  pathogenesis and the reconstitution of the immune
  system.

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Protocols

• P1056 Phase I/II Comparative PK Study of the
  Fixed Dose Combination of Stavudine, Lamivudine
  and Nevirapine as GPO-VIR Pediatric Chewable
  Tablets vs. the Individual Liquid Formulations in
  HIV-Infected Children gt6 months to lt13 years of
  Age in Thailand
• P1058 Intensive Pharmacokinetic Studies of
  Antiretroviral Drug Combinations in Children.
• P1066 A Multicenter, Open-Label, Non-comparative
  Study of the International Maternal, Pediatric,
  Adolescent AIDS Clinical Trials Group to Evaluate
  the Safety, Pharmacokinetics, and Antiretroviral
  Activity of MK-0518 in HIV-1 Infected Children
• P1066 is a fast track protocol to study an
  integrase inhibitor that is being collaboratively
  developed by Merck and IMPAACT.

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Complications

• Specific Aim 1 To evaluate safety and/or
  immunogenicity of approaches for the prevention
  and treatment of co-infections, ARV toxicities
  and associated metabolic complications, and
  developmental complications of HIV infection.
• Specific Aim 2 To conduct studies leading to the
  optimal use of vaccines, prophylactic regimens,
  and therapies for prevention and treatment of co-
  infections in HIV infected and exposed infants,
  children, adolescents, and pregnant women.
• Specific Aim 3 To conduct studies of licensed
  therapies for treatment of the complications of
  pediatric HIV infection and antiretroviral drugs
  including, but not limited to, metabolic
  disorders, neurological and psychiatric
  co-morbidity and other complications.

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Complications

• Long Term Follow-up Subcommittee A long term
  follow-up (LTF) subcommittee under the IMPAACT
  Complications Scientific committee was formed in
  January 2007 as a result of the meeting in
  Baltimore in December 2006. It was charged with
  the following responsibilities
• Development of the plan and implementation of the
  domestic long term registry with LEGACY (CDC).
• Develop the CRF that will be used by the
  registry.
• Plan and implement the closing of 219C with last
  participant visit by May 31, 2007.
• Set up an agreement between IMPAACT and Legacy
  and PHACS for sharing of 219C databases and
  specimens and sharing of registry data with
  Legacy.

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Protocols

• P1063 Phase I/II Dose-Finding And For Treatment
  Of PI-Associated Increased LDL-Cholesterol In
  HIV-Infected Children And Adolescents Version
  1.0 is anticipated to be the sites by April 2007.
  Sample size is 40 subjects. Safety Investigation
  Of Atorvastatin
• P1065 "Phase I/II study of safety and
  immunogenicity of quadrivalent meningococcal
  conjugate vaccine in HIV-infected youth." Sample
  size is 296 subjects (256 subjects (CD4 15)
  receiving one vs. two doses and 40 subjects
  (CD4lt15) receiving two doses of vaccine). This
  is the first large scale vaccine trial under the
  new IMPAACT leadership and network. This study
  will include the age and CD4 of the vast
  majority of HIV-infected youth seen at IMPAACT
  sites domestically, 11-lt25 years of age

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PMTCT

• Specific Aim 1 To develop and improve simple,
  safe and effective antiretroviral regimens to
  prevent mother-to-child HIV transmission in the
  perinatal period with special emphasis on low
  resource areas.
• Specific Aim 2 To optimize MTCT-related ARV
  treatment strategies to improve maternal and
  infant health through the reduction of
  antiretroviral resistance and improved safety.
• Specific Aim 3 To evaluate safe, simple, and
  effective interventions to prevent
  mother-to-child HIV transmission through
  breastfeeding

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PMTCT

• Specific Aim 4 To evaluate population based
  strategies for prevention of mother-to-child HIV
  transmission among childbearing populations
  receiving PMTCT care in limited resource settings
  or with limited access to structured antenatal
  PMTCT programs.
• Specific Aim 5 To determine the
  pharmacokinetics, safety, tolerability and
  toxicity of antiretrovirals used for prevention
  of mother-to-child HIV transmission and maternal
  health management.

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Protocols

• PACTG 394 A Phase I Study of the Safety and
  Pharmacokinetics of Tenofovir Disoproxil Fumarate
  in HIV-1 Infected Pregnant Women and Their
  Infants is the first study of tenofovir in
  pregnancy and will determine safety and PK for
  women and infants.
• P1043 Phase III Randomized Trial of the Safety
  and Efficacy of Three Neonatal Antiretroviral
  Regimens for Prevention of Intrapartum HIV-1
  Transmission. This study is being conducted in
  collaboration with the HPTN.and NICHD. Subjects
  are being enrolled at HPTN, NICHD and IMPAACT
  sites in Brazil, Argentina South Africa and the
  United States. All mothers are late presenters
  with no prior ARV treatment. The study will
  continue to enroll a potential 1,750 pairs and it
  should finish accrual in 2008. It is expected
  that an additional new study will be proposed
  using the winning arm of this study versus a new
  combination such as truvada (or other new ARV)
  with a backbone of ZDV for post exposure
  prophylaxis to follow this study. The first DSMB
  review was in the fall 2006 and it will be
  reviewed again by the DSMB in the spring 2008.

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Protocols

• P1032 Phase II Study of the Pharmacokinetics of
  NVP and the Incidence of NVP Resistance Mutations
  in HIV-Infected Women Receiving Single Dose
  Intrapartum Nevirapine with Concomitant
  Administration of ZDV/ddI or ZDV/ddI/LPV/r.
• P1025 "Perinatal Core Protocol." This protocol
  has enrolled over 1000 mother infant pairs and is
  the major study to evaluate the safety of new
  antiretrovirals in pregnancy. This study can
  provide important information on the potential
  changes in PMTCT, maternal genotypic resistance
  pre and postpartum and recurrent pregnancies.
  This study also provides important information
  about maternal adherence to drugs and neonatal
  safety of in utero exposure to ARV.

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Collaboration with HIV Prevention Trials Network
(HPTN)

• HPTN 057 A Phase I Open Label Trial of the
  Safety and Pharmacokinetics of Tenofovir
  Disoproxil Fumarate in HIV-1 Infected Pregnant
  Women and their Infants. This study is designed
  to examine Tenofovir in different doses in
  pregnant women and their infants in Africa and
  Brazil. It is currently enrolling in Africa and
  will open in Brazil in March/April. A second
  cohort using Truvada is expected to follow and
  PK will also be determined in the amniotic fluid
  when available as well as breast milk.
• HPTN 046 Phase III Trial to Determine the
  Efficacy and Safety of an Extended Regimen of
  Nevirapine in Infants Born to HIV Infected Women
  to Prevent Vertical HIV Transmission During
  Breastfeeding The study is open and will enroll
  at sites in South Africa, Zimbabwe, Tanzania, and
  Uganda

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Collaboration with Womens Health Initiative
Scientific Committee (WHISC)

• This is a newly formed committee jointly
  supported by the ACTG and IMPAACT to address
  issues surrounding womens health in the prenatal
  and peripartum period. The committee will have
  an equal number of members from both networks and
  two representatives from the committee will sit
  on the IMPAACT PMTCT Scientific Committee.
  Issues regarding sexual transmission and
  contraception will also be addressed.
• Capsule 209 Postpartum Depression in HIV
  Infected Women Biological Markers and Prognosis.
  

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Vaccine/Immuno-based Therapy (IBT)

• Specific Aim 1 Develop effective
  immunoprophylactic regimens to prevent breastmilk
  transmission of HIV-1.
• Specific Aim 2 Determine vaccine safety,
  immunogenicity and maintenance of suppressed
  viral loads in infants, children, and adolescents
  who were HIV infected prior to immunization.
• Specific Aim 3 Evaluate and implement an
  effective vaccine regimen to prevent sexual
  transmission of HIV-1 in adolescent and
  pre-adolescent populations.

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Protocols

• IMPAACT P1067 (formerly CAP 176) Phase I/II
  Trial to Evaluate the Safety, Tolerability,
  Immunogenicity and Optimal Dosing of the Merck
  Ad5-HIV-1 gag/pol/nef Trivalent Vaccine in
  HIV-Exposed Newborns. P1067 was approved on
  10/26/06 for fast track protocol development.
  Merck is the pharmaceutical sponsor and Elisabeth
  Glaser Pediatric AIDS Foundation is a co-sponsor.
  It is currently in Stage B of development.
  Chairs Coleen Cunningham and Betsy McFarland
• IMPAACT P1049 A Phase I/II Study of the Safety,
  Tolerability and Immunogenicity of a Topical
  Therapeutic DNA Dendritic Cell Vaccine (DermaVir
  Patch) in Children, Adolescents and Young Adults
  with HIV-1 Infection on HAART. P1049 is in the
  finalization stage, CSRC approval pending,
  (February 2007). Opening of this study will be
  dependent on the results of the AACTG adult
  DermaVir study (A5176) the same IND is being
  used.

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Protocols

• CAP 206 Preparing adolescents for HIV vaccine
  trial participation in South Africa. This was
  proposed on 10/31/06, and endorsed by the Vaccine
  SC on 1/22/07 to continue development in IMPAACT,
  with other countries to be included. Glenda Gray
  and Linda-Gail Bekker are the two lead
  investigators, from South Africa. A revised
  version with an estimated budget will be
  forwarded for further IMPAACT reviews.

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IMPAACT Organizational Structure
Operations Center Social Scientific Systems
(SSS) Network Community Coordinator
Network Executive Committee Group Chair Group
Vice Chairs S DMC PI Lab PI Ops Center
Director At-large members NIH Officers ICAB Reps

Statistical and Data Analysis Center (SDAC)
IMPAACT Community Advisory Board (ICAB)
Resource Committees
Scientific Oversight Committee Group Chair Group
Vice Chairs () SDMC PI Lab PI Scientific
Committee Chairs At-large members NIH
Officers ICAB Rep
Westat Coordinating Center for NICHD Clinical
Sites
Scientific Committees
Central Lab Steering Committee
Primary Therapy
Perinatal/Maternal
Laboratory Committee Virology Pharmacology Immunol
ogy Host Genetics Microbiology
Complications
Vaccine / IBT
ICAB Liaisons