Enrolment Predictors for an HIV prevention Open Label Clinical Trial

Thando Gwetu, Annalene Nel, Mariëtte Malherbe, Leonard Solai , Zonke Mabude

Presented at the 9th SAAIDS Conference, Durban ICC,

11-14 June 2019

Presentation Outline

• The past trial – IPM 027

• The present trial – IPM 032

• Objectives of current ancillary study

• Methods used

• Results

• Recommendations

Previous Phase III trials

• Parallel phase III Trials IPM 027 and MTN-020

• Conducted 2012-2016

• IPM Dapivirine Ring-004

IPM 027 and MTN-020 : Trial Designs

The Ring Study ASPIRE

ObjectivesSafety and efficacy

(fixed 2 year follow-up)

Safety and effectiveness

(HIV-1 endpoint driven)

Enrolment

Total: 1959 women2:1 randomization

ages 18-45

Active arm: 1307Placebo arm: 652

Total: 2629 women1:1 randomisation

ages 18-45

Active arm: 1313Placebo arm: 1316

All participants received a comprehensive HIV-1 prevention package

IPM 027 and MTN-020 : Results

• The IPM monthly vaginal ring containing dapivirine was safe and effective for HIV-1 risk reduction when used (~30%)

• HIV-1 protection was greater in subgroupswith evidence of better adherence to ring use

• Results demonstrated that a vaginal ring providing sustained delivery of an antiretroviral medication may be an important HIV-1 prevention option for women at risk for HIV-1 infection

Follow-up Open Label Extension (OLE) Clinical Trials

Phase III Trial Continuation

• IPM 032 and MTN-025

IPM

Dapivirine Vaginal Ring-004

The Dream & Hope Ring OLE Trials

IPM 032 MTN-025

Primary Objective Long-term safety and Adherence

Follow-up RegimensInitially 1-monthly

Routinely 3-monthly (2 additional rings)

Treatment Regimen 1-monthly ring replacement

Start date 2016

Objectives of the current ancillary IPM 032 Trial

• To investigate differences between

participants who chose to consent for further

study participation or declined to continue

follow-up study participation in the open-label

Dapivirine Vaginal Ring clinical trial (IPM 032)

at the MatCH research centre.

Method

• Data from MatCH Research Unit (Edendale)

which was one of six research centers that

conducted the IPM 032 trial.

• Retrospective analysis of recruitment data for

the IPM 032 trial.

• Data was collected for the period from August

2016 to March 2018.

• Predictors of recruitment were described.

Recruitment Summary

• 336/383 (87.7%) participants were eligible for

IPM 032 enrolment after exiting IPM 027

– 19 roll-overs and 317 previously exited.

• 26 participants were lost to follow-up

• 2 deceased participants who died during the

interval between the two trials

• 198/336 (63.5%) consented and 114/336

(36.5%) declined follow-up OLE involvement

Summary of IPM 032 Recruitment Statistics for the follow-up OLE at MatCH

Number of

Participants%

Total enrolled in IPM 027 (Phase III) 383

Eligible for IPM 032 upon exiting IPM 027 336 87.7 (336/383)

Lost to Follow-up/Death post exiting

IPM 02728 8.3 (28/336)

Participants eligible for IPM 032 Screening 312 92.9 (312/336)

Participants screened on-site for IPM 032 198 58.9 (198/336)

Decliners 114 33.9 (114/336)

Reasons provided by participants for declining further study involvement

Decliners

Number of

participants

114

%

33.9

(114/336)

Reasons for declining

Relocation 175.4

(17/312)

Not interested 54 17.3 (54/312)

Planning to fall pregnant 41.3

(4/312)

Working/Scholar 175.4

(17/312)

Other 206.4

(20/312)

HIV infection during inter-trial interval

• Participants reporting HIV seroconversion

post IPM 027 trial completion 6/336 (1.8%)

• At IPM 032 screening 12/336 (3.6%)

participants tested positive for HIV infection

post IPM 027 trial completion

• Total HIV seroconversions post IPM 027 trial

completion 18/336 (5.4%)

Predictors of OLE trial participation (p<0.05)

• Mean number of months since IPM 027 trial

completion at the time of IPM 032 recruitment

(<12 months participants vs. >12 months

decliners)

• Social harm occurrence in the IPM 027 trial

(social harm reported in IPM 027 vs. no social

harm reported in IPM 027)

• IP unblinding after exit from IPM 027 trial (IP vs.

placebo) was not a predictor of OLE participation

Previous IPM 027 factors associated with reduced odds of consenting to OLE follow-up

• Young age (<24 years)

• Low parity

• Single marital status

• Employment

• Student

Targeted strategies to enhance future OLE study recruitment efforts

• Identifying and addressing factors associated with lack of willingness to continue trial participation may improve some steps in the initial parent trial performance cascade and enhance subsequent follow-up for OLE trial participation.

• Investigators may formulate concrete actions to address any reported social harms as part of routine clinical research practice.

• Continued stakeholder and community engagementactivities between trials may assist OLE trial follow-up recruitment efforts particularly, as it may not be possible to shorten the interval time between Phase III trial exit and OLE trial start.

Acknowledgements

• IPM team

• MRU IPM study research participants

• Local stakeholders

• MRU research centre staff

The contents of this presentation are the responsibility of MatCH and do not necessarily reflect the views of IPM or IPM’s donors.

This work was supported by the International Partnership for Microbicides,

which receives generous support from: