HIV InfectionsPhase 3NCT00262106
Trial to Evaluate PRO 2000/5 Gels for the Prevention of Vaginally Acquired HIV Infection
A Phase 3 study testing PRO 2000/5 in people with HIV Infections and Gonorrhea, run by Endo USA Inc., a Keenova Therapeutics Company at 6 sites in 4 countries.
Trial summary
The objective of the study is to determine the efficacy and safety of 0.5% and 2% PRO 2000/5 gels compared to placebo in preventing vaginally acquired HIV infection. Read more about this study
- Who is it for?
- Ages 16 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV Infections, Gonorrhea, Chlamydial Infections
- What is being tested?
- PRO 2000/5
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9,404 participants
- Where
- 6 sitesin 4 countries
- Study dates
- Oct 2005to Sep 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Women aged 16 years and above at enrolment in Masaka and Mwanza, or aged 18 years and above at enrolment in the South African and Zambian sites
- Likely to be sexually active at entry and during follow-up
- Willing to undergo HIV testing at screening and approximately 12 weekly intervals, and additionally, if required, to determine HIV status
- HIV negative at screening according to the local HIV testing algorithm
- Willing to receive the HIV result before randomization
- Willing to use study gel as instructed
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- Willing to undergo regular speculum examinations and genital infection screens
- Willing to have regular urine pregnancy tests
- Willing to receive health education about condoms
- Willing and able to give informed consent
Who cannot join
- Unable or unwilling to provide a reliable method of contact for the field team
- Likely to move permanently out of the area within the next year
- Likely to have sex more than 14 times a week on a regular basis during the course of follow-up
- Using spermicides regularly
- Pregnant or within 6 weeks postpartum at enrollment
- Has Grade 3 clinical or laboratory abnormalities which are considered by the clinician or the Trial Management Group to make enrollment inadvisable
Show all 11Show fewer
- Requires referral for assessment of a clinically suspicious cervical lesion
- Treatment to the cervix, or to the womb through the cervix, within 30 days of enrolment
- Known latex allergy
- Participating, or has participated within 30 days of enrolment, in a clinical trial of an unlicensed product, microbicide, barrier method, or any other intervention likely to impact on the outcome of this trial
- Considered unlikely to be able to comply with the protocol
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
South Africa3 sites
Reproductive Health and HIV Research Unit, Chris Hani Baragwanath Hospital
Bertsham, 2013
Africa Centre for Health and Population Studies
Mtubatuba, 3935
HIV Prevention Research Unit, Medical Research Council
Westville, 3630
Uganda1 site
MRC Programme on AIDS in Uganda, Uganda Virus Research Institute
Entebbe
About this study
Official title: An International Multi-centre, Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of 0.5% and 2% PRO 2000/5 Gels for the Prevention of Vaginally Acquired HIV Infection
The objective of the study is to determine the efficacy and safety of 0.5% and 2% PRO 2000/5 gels compared to placebo in preventing vaginally acquired HIV infection.
Read the detailed description
The HIV pandemic continues with an estimated 13,000 new infections each day, the vast majority of which are acquired through heterosexual intercourse. Although consistent and correct use of condoms by men remains the most effective form of protection from heterosexually acquired HIV, women are not always able to negotiate condom use. An effective prophylactic vaccine remains a key objective, but development is slow because of virus variability and difficulty in determining the immunological correlates of protection. Vaginal microbicides are being developed in response to the urgent need for an HIV prevention method that women can control. Licensed spermicides containing nonoxynol-9 (N-9), which has potent anti-HIV activity in vitro, were the first products to be investigated as potential microbicides. However, the association of N-9 and other products belonging to this class (surfactants) with genital epithelial disruption, histologically determined genital inflammation, and reduction in populations of vaginal lactobacilli led to concerns that their use could enhance the risk of HIV transmission. Early Phase 3 studies of N-9 products yielded conflicting results, but more recently, a multicenter randomized placebo-controlled trial of a low dose N-9 formulation demonstrated an increased incidence of HIV infection in the N-9 group compared to placebo. These findings have intensified efforts to develop agents with a more favorable toxicity profile. At least four of these have entered trials to assess effectiveness in preventing vaginally acquired HIV infection: Buffer Gel, Carraguard, cellulose sulfate and PRO 2000/5 Gel. Protocol MDP 301 describes a randomized placebo-controlled trial design to explore the safety and efficacy of two concentrations of PRO 2000/5 Gel.
Participant recruitment and follow-up is complete. Between October 2005 and August 2008, 9404 eligible, sexually active, HIV-uninfected women were enrolled at six or more sites in Africa. Up until February 2008, participants were randomly assigned to 0.5% or 2% PRO 2000/5 Gel treatment arms or a placebo gel arm. Following a recommendation by the Independent Data Monitoring Committee that the 2% PRO2000/5 Gel treatment arm should not continue as there was no more than a small chance of demonstrating benefit, participants enrolled after February 13, 2008 were randomly assigned to the 0.5% PRO 2000/5 gel treatment arm or placebo arm. Participants were instructed to apply a single dose of study gel 1 hour or less before every act of vaginal intercourse using a single-use pre-filled applicator. Participants also receive risk-reduction counseling and condoms, and STD testing. Most study participants were followed for 12 months. A cohort of sero-discordant couples enrolled in Uganda was followed for up to 24 months.
The primary efficacy outcome measure is acquisition of HIV infection at the 12 month time point. Secondary outcomes include measures of HIV infection at the 6, 9 and more than 12 month time points, infection by HSV-2, Neisseria gonorrhoeae, Chlamydia trachomatis, and adverse events.
- Conditions
- HIV Infections, Gonorrhea, Chlamydial Infections, Genital Herpes
- Being tested
- PRO 2000/5, Placebo
- Keywords
- Administration, intravaginal, Anti-infective agents, Double blind method, Drug evaluation, Female, Gels, HIV infections/prevention and control, Microbicide, Naphthalenesulfonates/administration and dosage, Polymers/administration and dosage, Sexual behavior, Vaginal creams, foams and jellies, HIV Seronegativity, Genital Herpes Infections
- Medical subject headings
- HIV Infections, Gonorrhea, Chlamydia Infections, Herpes Genitalis, Sexual Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRO 2000/5Drug
Gel
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | placebo Receives: Drug: Placebo |
| PRO 2000/5 Gel 0.5% | Active comparator | PRO 2000/5 Gel 0.5% Receives: Drug: PRO 2000/5 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acquisition of HIV infection before or at the 12 month time point, confirmed in a central laboratory, in participants confirmed to be HIV negative at enrollment
Measured: 12 months
Grade 3 (severe) or 4 (life-threatening) clinical or laboratory adverse event confirmed on examination or repeat testing, respectively
Measured: 12 months
Secondary outcomes (5)
Acquisition of HIV infection before or at the 6, 9, or beyond 12 month time points, confirmed in a central laboratory, in participants confirmed to be HIV negative at enrollment
Measured: 6, 9 and 12 months
HSV-2 incidence rates by the 9 month time point in participants uninfected at enrollment. Although prevalence rates are high, 75% - 85% in some sites, data from feasibility studies indicate that incidence rates are also likely to be high
Measured: 9 months
HSV-2 incidence rates by the 12 month time point in participants uninfected at enrolment. Although prevalence rates are high, 75% - 85% in some sites, data from feasibility studies indicate that incidence rates are also likely to be high
Measured: 12 months
Cross-sectional prevalence of Neisseria gonorrhoeae at 24 weeks, determined by a positive nucleic acid amplification assay
Measured: 24 weeks/6 months
Cross-sectional prevalence of Chlamydia trachomatis at 24 weeks, determined by a positive nucleic acid amplification assay
Measured: 24 wks/6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2005 (estimated)
- Study startOct 2005
- Primary completionAug 2008
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 9,404 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medical Research Council, Department for International Development, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Sheena McCormack, MBBS, MSc, FRCP, Principal investigator, MRC Clinical Trials Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00262106
- Sponsor's protocol ID
- MDP301
- Other IDs
- ISRCTN64716212
- Status last verified
- Sep 2012
- First submitted
- 5 Dec 2005
- Last updated
- 10 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Van Damme L, Wright A, Depraetere K, Rosenstein I, Vandersmissen V, Poulter L, McKinlay M, Van Dyck E, Weber J, Profy A, Laga M, Kitchen V. A phase I study of a novel potential intravaginal microbicide, PRO 2000, in healthy sexually inactive women. Sex Transm Infect. 2000 Apr;76(2):126-30. doi: 10.1136/sti.76.2.126.
PubMed 10858715Mayer KH, Karim SA, Kelly C, Maslankowski L, Rees H, Profy AT, Day J, Welch J, Rosenberg Z; HIV Prevention Trials Network (HPTN) 020 Protocol Team. Safety and tolerability of vaginal PRO 2000 gel in sexually active HIV-uninfected and abstinent HIV-infected women. AIDS. 2003 Feb 14;17(3):321-9. doi: 10.1097/00002030-200302140-00005.
PubMed 12556685Morrow K, Rosen R, Richter L, Emans A, Forbes A, Day J, Morar N, Maslankowski L, Profy AT, Kelly C, Abdool Karim SS, Mayer KH. The acceptability of an investigational vaginal microbicide, PRO 2000 Gel, among women in a phase I clinical trial. J Womens Health (Larchmt). 2003 Sep;12(7):655-66. doi: 10.1089/154099903322404302.
PubMed 14583106Tabet SR, Callahan MM, Mauck CK, Gai F, Coletti AS, Profy AT, Moench TR, Soto-Torres LE, Poindexter III AN, Frezieres RG, Walsh TL, Kelly CW, Richardson BA, Van Damme L, Celum CL. Safety and acceptability of penile application of 2 candidate topical microbicides: BufferGel and PRO 2000 Gel: 3 randomized trials in healthy low-risk men and HIV-positive men. J Acquir Immune Defic Syndr. 2003 Aug 1;33(4):476-83. doi: 10.1097/00126334-200308010-00008.
PubMed 12869836
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An International Multi-centre, Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy and Safety of 0.5% and 2% PRO 2000/5 Gels for the Prevention of Vaginally Acquired HIV Infection
- ClinicalTrials.gov ID
- NCT00262106
- Acronym / sponsor ID
- MDP301
- Conditions
- HIV Infections, Gonorrhea, Chlamydial Infections, Genital Herpes
- Keywords
- Administration, intravaginal, Anti-infective agents, Double blind method, Drug evaluation, Female, Gels, HIV infections/prevention and control, Microbicide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9,404 participants (actual)
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics CompanyIndustry (pharma, biotech, devices)
- Collaborators
- Medical Research Council, Department for International Development, United Kingdom
- Study start
- Oct 2005
- Primary completion
- Aug 2008 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 6 Dec 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of the study is to determine the efficacy and safety of 0.5% and 2% PRO 2000/5 gels compared to placebo in preventing vaginally acquired HIV infection.
Detailed description
The HIV pandemic continues with an estimated 13,000 new infections each day, the vast majority of which are acquired through heterosexual intercourse. Although consistent and correct use of condoms by men remains the most effective form of protection from heterosexually acquired HIV, women are not always able to negotiate condom use. An effective prophylactic vaccine remains a key objective, but development is slow because of virus variability and difficulty in determining the immunological correlates of protection. Vaginal microbicides are being developed in response to the urgent need for an HIV prevention method that women can control. Licensed spermicides containing nonoxynol-9 (N-9), which has potent anti-HIV activity in vitro, were the first products to be investigated as potential microbicides. However, the association of N-9 and other products belonging to this class (surfactants) with genital epithelial disruption, histologically determined genital inflammation, and reduction in populations of vaginal lactobacilli led to concerns that their use could enhance the risk of HIV transmission. Early Phase 3 studies of N-9 products yielded conflicting results, but more recently, a multicenter randomized placebo-controlled trial of a low dose N-9 formulation demonstrated an increased incidence of HIV infection in the N-9 group compared to placebo. These findings have intensified efforts to develop agents with a more favorable toxicity profile. At least four of these have entered trials to assess effectiveness in preventing vaginally acquired HIV infection: Buffer Gel, Carraguard, cellulose sulfate and PRO 2000/5 Gel. Protocol MDP 301 describes a randomized placebo-controlled trial design to explore the safety and efficacy of two concentrations of PRO 2000/5 Gel.
Participant recruitment and follow-up is complete. Between October 2005 and August 2008, 9404 eligible, sexually active, HIV-uninfected women were enrolled at six or more sites in Africa. Up until February 2008, participants were randomly assigned to 0.5% or 2% PRO 2000/5 Gel treatment arms or a placebo gel arm. Following a recommendation by the Independent Data Monitoring Committee that the 2% PRO2000/5 Gel treatment arm should not continue as there was no more than a small chance of demonstrating benefit, participants enrolled after February 13, 2008 were randomly assigned to the 0.5% PRO 2000/5 gel treatment arm or placebo arm. Participants were instructed to apply a single dose of study gel 1 hour or less before every act of vaginal intercourse using a single-use pre-filled applicator. Participants also receive risk-reduction counseling and condoms, and STD testing. Most study participants were followed for 12 months. A cohort of sero-discordant couples enrolled in Uganda was followed for up to 24 months.
The primary efficacy outcome measure is acquisition of HIV infection at the 12 month time point. Secondary outcomes include measures of HIV infection at the 6, 9 and more than 12 month time points, infection by HSV-2, Neisseria gonorrhoeae, Chlamydia trachomatis, and adverse events.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placeboplacebo |
| PRO 2000/5 Gel 0.5% | Active comparator | Drug: PRO 2000/5PRO 2000/5 Gel 0.5% |
Who may qualify
- Ages
- 16 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Women aged 16 years and above at enrolment in Masaka and Mwanza, or aged 18 years and above at enrolment in the South African and Zambian sites
- Likely to be sexually active at entry and during follow-up
- Willing to undergo HIV testing at screening and approximately 12 weekly intervals, and additionally, if required, to determine HIV status
- HIV negative at screening according to the local HIV testing algorithm
- Willing to receive the HIV result before randomization
Key exclusion criteria (11 listed)
- Unable or unwilling to provide a reliable method of contact for the field team
- Likely to move permanently out of the area within the next year
- Likely to have sex more than 14 times a week on a regular basis during the course of follow-up
- Using spermicides regularly
- Pregnant or within 6 weeks postpartum at enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PRO 2000/5Gel | Drug | PRO 2000/5 Gel 0.5% |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Acquisition of HIV infection before or at the 12 month time point, confirmed in a central laboratory, in participants confirmed to be HIV negative at enrollment
Time frame: 12 months
Grade 3 (severe) or 4 (life-threatening) clinical or laboratory adverse event confirmed on examination or repeat testing, respectively
Time frame: 12 months
5 secondary outcomes
Acquisition of HIV infection before or at the 6, 9, or beyond 12 month time points, confirmed in a central laboratory, in participants confirmed to be HIV negative at enrollment
Time frame: 6, 9 and 12 months
HSV-2 incidence rates by the 9 month time point in participants uninfected at enrollment. Although prevalence rates are high, 75% - 85% in some sites, data from feasibility studies indicate that incidence rates are also likely to be high
Time frame: 9 months
HSV-2 incidence rates by the 12 month time point in participants uninfected at enrolment. Although prevalence rates are high, 75% - 85% in some sites, data from feasibility studies indicate that incidence rates are also likely to be high
Time frame: 12 months
Cross-sectional prevalence of Neisseria gonorrhoeae at 24 weeks, determined by a positive nucleic acid amplification assay
Time frame: 24 weeks/6 months
Cross-sectional prevalence of Chlamydia trachomatis at 24 weeks, determined by a positive nucleic acid amplification assay
Time frame: 24 wks/6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2012.
- Background: PubMed 10858715Van Damme L, Wright A, Depraetere K, Rosenstein I, Vandersmissen V, Poulter L, McKinlay M, Van Dyck E, Weber J, Profy A, Laga M, Kitchen V. A phase I study of a novel potential intravaginal microbicide, PRO 2000, in healthy sexually inactive women. Sex Transm Infect. 2000 Apr;76(2):126-30. doi: 10.1136/sti.76.2.126.
- Background: PubMed 12556685Mayer KH, Karim SA, Kelly C, Maslankowski L, Rees H, Profy AT, Day J, Welch J, Rosenberg Z; HIV Prevention Trials Network (HPTN) 020 Protocol Team. Safety and tolerability of vaginal PRO 2000 gel in sexually active HIV-uninfected and abstinent HIV-infected women. AIDS. 2003 Feb 14;17(3):321-9. doi: 10.1097/00002030-200302140-00005.
- Background: PubMed 14583106Morrow K, Rosen R, Richter L, Emans A, Forbes A, Day J, Morar N, Maslankowski L, Profy AT, Kelly C, Abdool Karim SS, Mayer KH. The acceptability of an investigational vaginal microbicide, PRO 2000 Gel, among women in a phase I clinical trial. J Womens Health (Larchmt). 2003 Sep;12(7):655-66. doi: 10.1089/154099903322404302.
- Background: PubMed 12869836Tabet SR, Callahan MM, Mauck CK, Gai F, Coletti AS, Profy AT, Moench TR, Soto-Torres LE, Poindexter III AN, Frezieres RG, Walsh TL, Kelly CW, Richardson BA, Van Damme L, Celum CL. Safety and acceptability of penile application of 2 candidate topical microbicides: BufferGel and PRO 2000 Gel: 3 randomized trials in healthy low-risk men and HIV-positive men. J Acquir Immune Defic Syndr. 2003 Aug 1;33(4):476-83. doi: 10.1097/00126334-200308010-00008.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sheena McCormack, MBBS, MSc, FRCP principal investigator
MRC Clinical Trials Unit
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PRO 2000/5 in people with HIV Infections and Gonorrhea, run by Endo USA Inc., a Keenova Therapeutics Company at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in South Africa, Tanzania, Uganda, Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acquisition of HIV infection before or at the 12 month time point, confirmed in a central laboratory, in participants confirmed to be HIV negative at enrollment (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00262106, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2012; AzTrials last refreshed its copy on 26 Oct 2026.