# Presentation: 185922

## LESSONS LEARNED FROM THE PHASE III TRIAL OF COL-1492, A NONOXYNOL-9 VAGINAL GEL, ON HIV-1 TRANSMISSION IN FEMALE SEX WORKERS

**LESSONS LEARNED FROM THE PHASE III TRIAL OF COL-1492, A NONOXYNOL-9 VAGINAL GEL, ON HIV-1 TRANSMISSION IN FEMALE SEX WORKERS**

**Lut Van Damme**

## UNAIDS studies with COL-1492

- COL-1492 = Advantage S®
- 52.5 mg N-9
- bio-adhesive carrier
- 		good coverage of vaginal walls and cervix
- 	 	immediate availability of N-9
- Placebo = Replens®
- vaginal moisturiser
- more viscous than Advantage S®
- lower pH

## Safety trials with COL-1492

- N = 534
- COL-1492, placebo and no-treatment arm

**Low risk women**

**High**** ****risk women**

**CONCLUSION : low incidence of and no difference in lesions with an epithelial disruption among the arms**

- N = 320
- COL-1492, and placebo arm

## Phase III trial: HIV incidence* 

|  | 
COL-1492 | 
Placebo |  
p   |
| --- | --- | --- | --- |
|  |  |  |  |
|  |  |  |  |
|  | 14.7 | 10.3 | 0.047 |
|  |  |  |  |
|  |  |  |  |
|  |  |  |  |
|  |  |  |  |

** per 100 woman-years*

## Methodological and Ethical Issues

- Methodological Issues:
**	****	****-placebo**
**	****	****-no treatment arm**
**	****	****-behavioural data ****	****   ****	**** collection**
**	****	****-safety assessment**
**	****	****-study population**
**	****	****-p-value**

-   Ethical Issues:
- 	     **-informed consent**
**	****      ****-HIV treatment**

## Placebo

- “Ideal” placebo:
- no impact on HIV incidence
- indistinguishable from experimental product
- Has been developed and is currently being tested for safety by CONRAD

## No treatment arm

**Open-label study**
- prospective bias
- impact on loss-to-follow-up
- impact on recruitment potential
- sharing of products

**If 3-arm trial: sample size  ↑↑**

## Behavioral Data Collection

**Necessary ?**
- Intent-to-Treat analysis
- Exploratory analyses
**How ?**
- Coital Log Chart
- Direct interview
- ACASI

## Assessment of Safety and Preliminary Effectiveness

**In COL-1492: risk of HIV when lesion with breach twice the risk without such a lesion**
**Determination of net importance of findings: only in phase III**

## Study Population

**Generalizability of results**
**Withhold potential beneficial product when trials done among high frequency users?**
**High frequency use assessment: **
**    ****VERY important**

## p-value

| Type I error | Months of 
follow up | N per
group | Total N | Events
required |
| --- | --- | --- | --- | --- |
| .05 | 12 | 1277 | 2554 | 64 |
|  |  |  |  |  |
| .01 | 12 | 1899 | 3798 | 95 |
|  |  |  |  |  |
| .001 | 12 | 2776 | 5392 | 138 |

-  Assumptions: A 4% annual HIV incidence in the placebo arm;
-     _**50% effectiveness**_; _**80% power**_; annual retention of 80%

## CONRAD’s Approach

**2 arms**
**RCT**
**HEC placebo**
**80% power**
**.05 significance level**
**50% effectiveness**
**1-year retention: 80%**
**1 year follow-up**

## Informed Consent Process

**Not a “once and for all” event**
**Questions to assess comprehension**
- after obtaining consent
- during trial participation
**Some beliefs extremely difficult to change**

## HIV Treatment

**STI treatment for all women at screening **
**	****and follow-up**
**ART?**
**	****Make a fund available to investigators for seroconvertors during follow-up**
**Prevention of opportunistic infections**