Microbicides The Population Council Experience

MicrobicidesThe Population CouncilExperience and FutureDirectionsMicrobicidesThe Population CouncilExperience and FutureDirections

Don E. Waldron

Medical Director

Don E. Waldron

Medical Director

HistoryHistory

Early research in the late 80’s identified largemolecular structured entity derived from seaweed as a potential HIV blocking agent

In vitro tissue studies showed Carraguard®protective against HIV

In vivo mouse and monkey experimentsdemonstrated blocking

Methyl cellulose placebo was not protectiveagainst HIV

Early research in the late 80’s identified largemolecular structured entity derived from seaweed as a potential HIV blocking agent

In vitro tissue studies showed Carraguard®protective against HIV

In vivo mouse and monkey experimentsdemonstrated blocking

Methyl cellulose placebo was not protectiveagainst HIV

Phase IPhase I

Trials conducted in many countriesincluding South Africa (SA)

Results showed that Carraguard® is safeand acceptable

Couples study for male tolerance andacceptability is under analysis

Two studies in HIV positive cohorts areunderway

Trials conducted in many countriesincluding South Africa (SA)

Results showed that Carraguard® is safeand acceptable

Couples study for male tolerance andacceptability is under analysis

Two studies in HIV positive cohorts areunderway

Phase II Experience(Preliminary Observations)Phase II Experience(Preliminary Observations)

Two trials conducted in Thailand (165) andSA (400), two arms, Intent to Treat (ITT)

Safety and acceptability confirmed

Condom use similar in both arms withcondom usage in Thailand higher than in SA

Recruitment and retention similar for botharms

Seroconversions only in SA, 8 in each arm

Two trials conducted in Thailand (165) andSA (400), two arms, Intent to Treat (ITT)

Safety and acceptability confirmed

Condom use similar in both arms withcondom usage in Thailand higher than in SA

Recruitment and retention similar for botharms

Seroconversions only in SA, 8 in each arm

Gel & Condom Usage During Sex Acts,Phase II SA (ITT)Gel & Condom Usage During Sex Acts,Phase II SA (ITT)

Phase III Overall DesignConsiderationsPhase III Overall DesignConsiderations

A classic placebo controlled, two arm, doubleblind ITT trial in 4500 non infected women inSA

The active arm Carraguard® and a methylcellulose placebo

Maximum trial duration is 48 months with a24 month maximum subject participation

We are examining a design of closing the trial12 months after the last patient is enrolled

A classic placebo controlled, two arm, doubleblind ITT trial in 4500 non infected women inSA

The active arm Carraguard® and a methylcellulose placebo

Maximum trial duration is 48 months with a24 month maximum subject participation

We are examining a design of closing the trial12 months after the last patient is enrolled

Trial CriteriaTrial Criteria

Two major exclusion criteria

–Women who test positive for HIV

–Pregnant women

Women with STIs will be accepted

Primary endpoint: HIV seroconversion

Safety endpoints: STIs & vaginal lesions

Two major exclusion criteria

–Women who test positive for HIV

–Pregnant women

Women with STIs will be accepted

Primary endpoint: HIV seroconversion

Safety endpoints: STIs & vaginal lesions

Compliance MethodsCompliance Methods

Compliance will be tested using severalmethods

–Visit questionnaires administered by clinic staff

–Applicator tracking using bar code

–Compliance with visit schedule