hiv vaccine clinical trial updates and novel vaccine design (punnee pitisuttithum)

8/4/2019 HIV Vaccine Clinical Trial Updates and Novel Vaccine Design (Punnee Pitisuttithum)

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Clinical Trials and Trial Design

Punnee Pitisuttithum, MBBS,DTM&H,FRCPT

Faculty of Tropical Medicine, Mahidol University

AIDSVACCINE Conference ,BKK

Sept 13,2011


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Ongoing Trials of New HIV Prevention Optionsworldwide

www.avac.org (May 2009)
http://www.avac.org/http://www.avac.org/


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Working on the Puzzle of VaccineInduced Protection


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Recombinant protein (gp120)

synthetic peptides (V3)

naked DNA

Live-recombinant vectorsvirus-Ad5, Ad26, MVA,NYVA

Bacteria-rBCG

Whole-inactivated virus

Live-attenuated virus

HIV vaccine constructs


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Cumulative Vaccine Efficacy Over Time


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Randomized, Double Blind Evaluation of Late

Boost Strategies for HIV-uninfectedParticipants in the HIV Vaccine Efficacy Trial

RV 144: Aventis Pasteur* Live

Recombinant ALVAC-HIV (vCP1521) Priming

with VaxGen**gp120 B/E (AIDSVAXB/E) Boosting in HIV-uninfected Thai Adults

Punnee Pitisuttithum MD,FRCPTMahidol University


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Primary Objective

Characterize and compare cellular and humoral

responses in the systemic and mucosalcompartments following late boosts for eachstrategy tested

Assess the safety and tolerability of late boostregimens consisting of the RV144 combination ofregimen or one component of the combination(AIDSVAX B/E or ALVAC-HIV)


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Evaluate mucosal immune responses (humoral

and cellular) for each boost regimen Evaluate systemic and mucosal activation of

T cell target for HIV infection for eachboost regimen

compare innate immune responses betweeneach boost regimen

Define the residual humoral and cellular immuneresponse since completing the primaryprime-boost series within RV144

Secondary Objective


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GROUP

Number of

subjectsVaccine/Placebo

Week of Study

0 24

I

45 ALVAC-HIV +

AIDSVAXB/EALVAC-HIV +

AIDSVAXB/E

9 ALVAC-HIV placebo+

AIDSVAXplacebo

ALVAC-HIVplacebo +

AIDSVAXplacebo

II

45 AIDSVAXB/E AIDSVAXB/E

9 AIDSVAXplacebo AIDSVAXplacebo

III

45 ALVAC-HIV ALVAC-HIV

9 ALVAC-HIV placebo ALVAC-HIV

placebo

Mode of Administration:


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Visit no. 1 2 3 4a 4b 5 6 6a 7 8 Exit

week 0 2 24 26 48 50 72 74Informed Consent X

Test of understanding X

Enrollment & Randomization X

Vaccination & Diary card X X

Physical exam X X X X X X X

Medical history & Vital Signs X X X X X X X X

Concomitant Medications X X X X X X X

HIV Risk Reduction X X X X X X X X

Counseling (pre and/or post) X X X X X X X X X

Urine Pregnancy Test X X X X X

Urine dipstick, CBC, Cr., ALT X X

STI diagnostic tests X

Pap Smear HPV tests X

Schedule of Assessments


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Others ongoing Trials (1)

Phase Trial ID Strategy CandidateNo of

subject Clade

I Ad26.ENVA.01 Viral Vector Adeno

Ad26.EnvA-01 48 A

I Ad5HVR48.ENVA.01 Viral Vector- Adeno

Ad5HVR48.ENVA.01

48 A

I CN54gp140-hsp70Conjugate vaccine

Protein CN54gp140

I DCVax-001 Protein DCVax-001

I Extention HVTN073E/SAAVI 102

Protein Sub Cgp140

I HIVIS 05 DNA/ViralVector-Pox

HIVIS-DNA/MVA-CMDR

24

I HIVIS 07 DNA/ViralVector-Pox

48


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Ongoing Trials (2)


subject

Clade

I HPTN 027 Viral Vector Pox

ALVAC-HIVvCP1521

50

I HVRF-380-131004 Protein Vichrepol 15

I HVTN 073 DNA/Viral

Vector-Pox

SAAVI DNA-

C2/SAAVIMVA-C

48 C

I HVTN 076 DNA/ViralVector-Adeno

VRC-HIVDNA016-00-VP/VRC-HIVADV014-00-VP

45 A,B,C

Ib HVTN 077 Viral Vector-Adeno/ViralVector-Adeno/DNA

VRC-HIVADV027-00-VP/VRC-HIVADV038-00-VP/VRC-HIVDNA

044-00-VP

192


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subject

Clade

Ib HVTN 078 Viral VectorPox/viralVector-Adeno

NYVAC-B/VRC-HIVADV038-00-VP

80

I HVTN 082 DNA/ViralVector-Adeno

VRC-HIVDNA016-00-VP/VRC-HIVADV014-00-VP

I HVTN 083 Viral Vector-Adeno/ViralVector-

Adeno /ViralVector-Adeno

VRC-HIVADV038-00-VP/VRC-HIVADV

052-00-P/VRC-HIVADV027-00-VP

180 A,B

I/II HVTN 084 Viral Vector-Adeno/ViralVector-Adeno

VRC-HIVADV054-VP/VRC-HIVAVD014-00-VP

Ongoing Trials(3)


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subject

Clade

I HVTN 086, SAAVI103

Viral Vector Pox/DNA/Protein

SAAVI MVA-C/SAAVI DNA-C2/Oligomericgp140/MF59

184

IIa HVTN 205 DNA/ViralVector-Pox

pGA2/JS7DNA/MVA/HIV62

225 B

II HVTN 505 DNA/ViralVector-Adeno

VRC-HIVDNA016-00-VP/VRC-HIVADV

014-00-VP

2,200 B

I IAVI B001 Viral Vector-Adeno/ViralVector-Adeno

Ad35-GRIN/ENV/Ad35-GRIN/ENV

56 A

Ongoing Trials (4)


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Ongoing Trials (5)


subject

Clade

I IAVI B002 Protein/Protein/Viral Vector Adeno

AdjuvantedGSKinvestigationalHIV vaccinefomulation 1 /

AdjuvantedGSKinvestigationalHIV vaccinefomulation 2/Ad35-GRIN

140

I IAVI B003 Viral Vector-Adeno/ViralVector-Adeno

Ad26.EnvA-01/Ad35-ENV

212

I MV1-F4 Viral Vector-

Replicating

Measles

Vector-GSK


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Ongoing Trials (6)

Phase Trial ID Strategy Candidate

No of

subject Clade

I/II NCHECR-AE1 DNA/ViralVector-Pox

pHIS-HIV-AE/rFPV-HIV-AE

8

I PedVacc001&

PedVacc002

Viral Vector-

Pox

MVA.HIVA 48

I RV138; B011 Viral Vector-Pox

ALVAC-HIVMN120TMGstrain (vCP205)

36

I RV 262 DNA/Viral

Vector-Pox

Pennvax-G/

MVA-CMDR

92 A,B,C,

D,EI TAMOVAC-01-MZ DNA/Viral

Vector-PoxHIVIS-DNA/MVA-CMDR

24

I Three Russian HIVVaccines

21


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Ongoing Trials (7)

Phase Trial ID Strategy Candidate

No of

subject Clade

I Tiantian vacciniaHIV Vaccine

DNA / ViralVector-Replicating

Chinese DNA /Tiantianvaccinia

80

I VRC 012 (07-1-

0167)

Viral Vector-

Adeno/ViralVector-Adeno

VRC-HIVADV

027-00-VP/VRC-HIVADV038-00-VP

35 A

I VRC 015 (08-1-0171)

Viral Vector-Adeno

VRC-HIVADV014-00-VP

31 A,B,C

I VRC 016 DNA/ViralVector-Adeno

VRC-HIVDMA016-00-VP/VRC-HIVADV014-00-VP

24


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Trial Design:Why are Phase IIb trials an important

step in evaluating AIDS vaccine?

Phase I,II trials involve a small number of volunteers

Safety and immunogenicity of vaccineThe phase III trials

require large numbers of volunteer take a long time to set up and complete be the final step before a vaccine can getapproval for licensure for FDA


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Vaccine being tested will be effective To be not designed to establish the efficacy

The number of volunteers is smaller,only 2-5,000 volunteers Easier to design and manage and less cost

Disadvantage

Phase IIb trials are run in smaller

populations, the precision of the trial is less

A vaccine can not be licensed based on theresults of Phase IIb testing


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Why are test of concept trials especiallyuseful for AIDS vaccines?

The first Phase IIb trial of an AIDS vaccinecandidate, which is being conducted by Merckand the HIV Vaccine Trials Network.

MRKAd5 in approximately 3,000 volunteers.The MRKAd5 candidate primarily generates acellular immune responseUS-based Merck and GlaxoSmithKline

Biologicals tested their respective vaccinecandidates for human papilloma virus in PhaseIIb trials.


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Adaptive Clinical Trial Design

Test multiple candidates simultaneously, Comparing to the same placebo group in a

randomized, blinded, phase IIb trial

to if they are able to prevent HIV infection Adaptive trials allow investigators to modify

the trial while its underway

More flexibility to drop candidatesthat dont seem to be working It would allow investigators to rank

the different candidates

Trial Design


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The trials were blindedmeaning volunteers werenot aware during the trial whether they hadreceived the vaccine or the placebo

Safety Monitoring Boards (DSMB) collected and

analyzed safety and efficacy data at pre-specifiedtime points during the course of the trials andcould then determine whether the trials shouldcontinue or be stopped either for safety reasons

or for futility The interim data indicates that a vaccine candidate

is not meeting pre-determined efficacy levels



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Researchers have the flexibility to shrink or drop

that arm of the study while continuing the others

Instance, in a trial population with a 4% annual

HIV incidence rate and 2,000 volunteers per

group

To be possible to reach a decision point in

approximately 20 months



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One important caveat of adaptive clinical trial

is that they are not suitable for licensure

More frequent interim data analyses that are

conducted in adaptive trials

The flexibility that researchers will have to

respond to the data

To reduce the overall power of the study

To difficult to interpret the result


hiv vaccine clinical trial updates and novel vaccine design (punnee pitisuttithum)

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