Herpes Simplex IIPhase 1NCT00331032
VivaGel™ in Healthy Young Women
A Phase 1 study testing 3% w/w SPL7013 Gel in people with Herpes Simplex II, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.
Trial summary
The purpose of this study is to test the safety and tolerability of a medication applied vaginally twice daily in females versus placebo (inactive substance). Study participants will include 60 women, ages 18-24, non-pregnant, previously sexually active, Human Immunodeficiency Virus (HIV) negative and sexually… Read more about this study
- Who is it for?
- Ages 18 to 24 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Herpes Simplex II
- What is being tested?
- 3% w/w SPL7013 Gel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Dec 2006to Nov 2007
- Phase
- Phase 1
- 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 18 to 24 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subject has voluntarily given written informed consent to participate in the study.
- Subject is female and aged between 18 and 24 years, inclusive.
- Subject is sexually active.
- Subject should have a menstrual cycle length of at least 25 days.
- Subject is in good health, as determined by medical history, a baseline physical examination, and clinical laboratory tests.
- Subject agrees to comply with all study procedures.
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- Subject has no significant abnormal vaginal microflora (abnormal flora defined as Nugent score greater than or equal to 7) at screening.
- Subject has a negative urine pregnancy test at screening and enrollment.
- Participant must agree to abstain from all sexual activities involving intercourse or other forms of vaginal penetration 7 days prior to the Enrollment Visit through the completion of all follow-up visits and procedures.
Who cannot join
- Subject has received or is anticipated to receive a new prescription systemic or topical medication within 14 days prior to the start of dosing. Subjects may be enrolled if stable on existing therapy as determined by the Principal Investigator.
- Subject has received any new long-acting treatments [e.g. depot formulation including medroxyprogesterone acetate (DMPA) form of hormonal birth control]. Subjects may be enrolled if stable (greater than 3 months) on existing therapy as determined by the Principal Investigator.
- Subject has received an investigational drug within 30 days or 10 half-lives of the drug, whichever is longer, prior to entering this study, or is planning to receive another investigational drug while participating in this study.
- Subject has a history of significant drug allergy.
- Subject has a history of latex allergy.
- Biological and hematological parameters are outside of the laboratory's normal reference ranges. Subjects with grade 1 laboratory abnormalities can be included if the Principal Investigator judges that the deviations are not clinically relevant.
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- Subject has a clinically significant history of systemic allergic disease (e.g., clinically significant urticaria, clinically significant atopic dermatitis).
- Subject has a history of recurrent vaginal infections, irritation or localized reaction to vaginally applied agents.
- Subject has an unpredictable or irregular menstrual cycle that will not allow scheduling of the colposcopic examinations outside menstruation as required for the protocol.
- Subject has a recent (within 3 months) history of intermenstrual bleeding.
- Subject has an active, uncontrolled medical condition (e.g., neurological, gastrointestinal, renal, hepatic, cardiovascular, pulmonary, metabolic, endocrine, hematological, genitourinary or other major disorder), or psychiatric illness (e.g., depression, schizophrenia).
- Subject had a clinically significant illness within 30 days prior to screening.
- Subject has used a vaginal preparation within 30 days prior to screening.
- Subject has a clinically detectable genital abnormality (i.e. vulvar, vaginal, cervical, perianal ulcer and/or deep epithelial disruption).
- Subject has signs, as seen on pelvic exam, consistent with an Sexually Transmitted Infection (STI), other genital tract infection - other than bacterial vaginosis (BV) - or trauma, including but not limited to: vaginitis, cervicitis, and laboratory findings indicative of genital tract infection other than asymptomatic BV.
- Note: Signs of asymptomatic BV include the presence of white to grey homogeneous discharge, positive whiff test (amine odor) with addition of KOH, pH>4.5, presence of clue cells, decrease in lactobacilli morphotypes, and increase in non-lactobacilli morphotypes. Women with clinical or gram stain evidence of BV and symptoms (discharge, odor, itching), or yeast colonization and symptoms at screening should be treated and re-evaluated for inclusion. Women without BV symptoms, but who have clinical or gram stain evidence of BV, or asymptomatic yeast colonization, are eligible.
- Subject tests positive for serum antibodies to human immunodeficiency virus 1 and/or 2 (HIV-1 and/or HIV-2).
- Subject tests positive for serum antibodies to herpes simplex virus, type 2 (HSV-2).
- Subject tests positive for Chlamydia, gonorrhea, trichomonas, syphilis or a urinary tract infection at screening or enrollment.
- Note: Women who have an STI or are symptomatic and have a positive urine culture (urinary tract infection - UTI) at screening will be referred for and/or given treatment. Following completion of treatment, women with a negative repeat test may be reconsidered for study participation.
- Subject has an abnormal Pap smear at screening.
- Subject has history in the last three months of: an IUD, vaginal contraceptive ring, a pregnancy, cervical cryotherapy or laser therapy, gynecologic surgery.
- Subject is currently breast feeding or is planning on breast feeding while participating in this study.
- Subject, in the opinion of the Principal Investigator, should not participate in the study.
- Women with colposcopic evidence of deep epithelial disruption at the enrollment visit will be excluded. In addition, based on the investigator's (medical examiner's) opinion any colposcopic finding or any finding (normal or abnormal) that could interfere with colposcopic examinations may also lead to exclusion. In this case, the investigator may have the subject return within the screening window to determine if the abnormality has cleared, and if she is eligible for enrollment.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: An Expanded Phase I Randomized Placebo Controlled Trial of the Safety and Tolerability of 3 Percent w/w SPL7013 Gel (VivaGel™) in Healthy Young Women When Administered Twice Daily for 14 Days
The purpose of this study is to test the safety and tolerability of a medication applied vaginally twice daily in females versus placebo (inactive substance). Study participants will include 60 women, ages 18-24, non-pregnant, previously sexually active, Human Immunodeficiency Virus (HIV) negative and sexually transmitted infection (STI) free, in San Francisco or Kisuma, Kenya. Each study participant will be followed for 14 days of product use and an additional 7 days for safety assessments. Study procedures will include a physical exam with a pap smear, urine testing, blood sample testing, and a colposcopy (exam of the vagina and cervix using a lighted magnifying instrument). Information learned from this study may help to develop a safe and effective medication that could prevent herpes simplex virus and HIV. Participants may be involved in study related procedures for up to 55 days.
Read the detailed description
Over half of global human immunodeficiency virus (HIV) infections occur among those aged 18-24 years and young women are at a particularly high risk of acquiring genital herpes caused by herpes simplex virus type 2 (HSV-2) and other sexually transmitted infections (STI). This is a phase I, randomized, double blind, clinical trial of twice-daily vaginal VivaGel™ (n equals 40) versus placebo gel (n equals 20). The primary aim of this protocol is to test the safety and tolerability of VivaGel™ in young women, with the long-term aim of testing the efficacy of this compound in preventing HSV-2 in a future phase II/III trial. A total of 60 young women aged 18-24, non-pregnant, previously sexually active, STI and HIV free, in San Francisco and in Kisumu, Kenya will participate in this study. Eligibility screening will include medical history, pelvic exam with a Pap smear, urine pregnancy testing, HIV and STI counseling and testing, hematology testing and liver and renal function testing. Eligible participants will undergo a pelvic exam with colposcopy. Vaginal swabs will be collected to evaluate H2O2-producing lactobacilli and Gram stain, Chlamydia, gonorrhea, and prostate specific antigen (PSA) (to confirm lack of exposure to semen). Endocervical samples will be collected to measure immunological status. Blood will be collected to conduct hematology and liver and renal function testing, and plasma will be collected and stored for batch testing. Subjects will be provided with the investigational product or placebo, given a Daily Study Record, instructed how to use the product, complete the Daily Study Record, and report any adverse events (AEs). Follow-up visits will occur on Days 2, 7, 14, and 21. The primary study objective will be to determine the safety and tolerability of VivaGel™ applied vaginally twice daily for 14 days in HIV negative and STI-free young women. Safety assessments, comparing the VivaGel™ group to the placebo gel group, will include: incidence and severity of AEs, including genital tract signs and symptoms and mucosal changes as observed by colposcopy; vaginal microflora, including colonization with H2O2-producing lactobacilli; and laboratory parameters, including serum chemistry and hematology. The tolerability assessment, comparing the VivaGel™ group to the placebo gel group will include the proportion of participants who discontinued product use due to overt (i.e. observable) AEs, ascertained through a standardized questionnaire. The secondary objective of the study will be to report the effect of VivaGel™ applied vaginally twice daily for 14 days on the immune microenvironment in the lower genital tract of young women. Specifically, this will be tested by determining its effect on: the number and activation levels of endocervical immune cell populations; Secretory Leukocyte Protease Inhibitor (SLPI) levels; innate mucosal defenses, including local levels of cytokines in cervical secretions, and Toll-Like Receptor (TLR) expression by cervical immune cells; and the presence and expression levels of the HIV co-receptors CCR5 and CXCR4, and of their principal chemokine ligands by endocervical immune cells.
- Conditions
- Herpes Simplex II
- Being tested
- 3% w/w SPL7013 Gel, Placebo
- Keywords
- VivaGel™, sexually transmitted, microbicide, herpes simplex
- Medical subject headings
- Herpes Simplex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3% w/w SPL7013 GelDrug
Twice-daily vaginal application of 3.5 g of VivaGel™ (Carbopol®-based gel with 3% w/w SPL7013) in single use pre-filled applicators.
PlaceboDrug
Placebo gel (Carbopol®-based formulation alone) in single use pre-filled applicators.
| Study group | Role | What they receive |
|---|---|---|
| 1: 3% w/w SPL7013 Gel | Experimental | 40 subjects VivaGel™. Receives: Drug: 3% w/w SPL7013 Gel |
| 2: Placebo | Placebo comparator | 20 subjects placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability will assess the degree to which overt Adverse Events can be tolerated by the study participants.
Measured: Tolerability measures will be assessed at Days 2, 7, and 14 visits.
Safety will be assessed by laboratory tests and clinical Adverse Events.
Measured: Safety assessed after 2, 7, and 14 days of product use and 7 days following the completion of product use (Day 21).
Secondary outcomes (4)
Presence and expression levels of Human Immunodeficiency Virus co-receptors CCR5 and CXCR4, and their principal chemokine ligands by endocervical immune cells.
Measured: Immunologic factors of the genital tract will be measured using cervicovaginal specimens collected at enrollment, Day 7, Day 14, and Day 21.
Secretory Leukocyte Protease Inhibitor levels.
Measured: Immunologic factors of the genital tract will be measured using cervicovaginal specimens collected at enrollment, Day 7, Day 14, and Day 21.
Number and activation levels of endocervical immune cell populations.
Measured: Immunologic factors of the genital tract will be measured using cervicovaginal specimens collected at enrollment, Day 7, Day 14, and Day 21.
Innate mucosal defenses, including local levels of cytokines in cervical secretions, and Toll-Like Receptor expression by cervical immune cells.
Measured: Immunologic factors of the genital tract will be measured using cervicovaginal specimens collected at enrollment, Day 7, Day 14, and Day 21.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2006 (estimated)
- Study startDec 2006
- Primary completionNov 2007
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Herpes Simplex IIStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00331032
- Sponsor's protocol ID
- 05-0121
- Other IDs
- SPL7013-004
- Status last verified
- Aug 2013
- First submitted
- 25 May 2006
- Last updated
- 23 Aug 2013
- Results posted
- No
Publications
Cohen CR, Brown J, Moscicki AB, Bukusi EA, Paull JR, Price CF, Shiboski S. A phase I randomized placebo controlled trial of the safety of 3% SPL7013 Gel (VivaGel(R)) in healthy young women administered twice daily for 14 days. PLoS One. 2011 Jan 20;6(1):e16258. doi: 10.1371/journal.pone.0016258.
PubMed 21311578
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Expanded Phase I Randomized Placebo Controlled Trial of the Safety and Tolerability of 3 Percent w/w SPL7013 Gel (VivaGel™) in Healthy Young Women When Administered Twice Daily for 14 Days
- ClinicalTrials.gov ID
- NCT00331032
- Acronym / sponsor ID
- 05-0121
- Conditions
- Herpes Simplex II
- Keywords
- VivaGel™, sexually transmitted, microbicide, herpes simplex
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Dec 2006
- Primary completion
- Nov 2007 (actual)
- Study completion
- Nov 2007 (actual)
- First posted
- 29 May 2006 (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 purpose of this study is to test the safety and tolerability of a medication applied vaginally twice daily in females versus placebo (inactive substance). Study participants will include 60 women, ages 18-24, non-pregnant, previously sexually active, Human Immunodeficiency Virus (HIV) negative and sexually transmitted infection (STI) free, in San Francisco or Kisuma, Kenya. Each study participant will be followed for 14 days of product use and an additional 7 days for safety assessments. Study procedures will include a physical exam with a pap smear, urine testing, blood sample testing, and a colposcopy (exam of the vagina and cervix using a lighted magnifying instrument). Information learned from this study may help to develop a safe and effective medication that could prevent herpes simplex virus and HIV. Participants may be involved in study related procedures for up to 55 days.
Detailed description
Over half of global human immunodeficiency virus (HIV) infections occur among those aged 18-24 years and young women are at a particularly high risk of acquiring genital herpes caused by herpes simplex virus type 2 (HSV-2) and other sexually transmitted infections (STI). This is a phase I, randomized, double blind, clinical trial of twice-daily vaginal VivaGel™ (n equals 40) versus placebo gel (n equals 20). The primary aim of this protocol is to test the safety and tolerability of VivaGel™ in young women, with the long-term aim of testing the efficacy of this compound in preventing HSV-2 in a future phase II/III trial. A total of 60 young women aged 18-24, non-pregnant, previously sexually active, STI and HIV free, in San Francisco and in Kisumu, Kenya will participate in this study. Eligibility screening will include medical history, pelvic exam with a Pap smear, urine pregnancy testing, HIV and STI counseling and testing, hematology testing and liver and renal function testing. Eligible participants will undergo a pelvic exam with colposcopy. Vaginal swabs will be collected to evaluate H2O2-producing lactobacilli and Gram stain, Chlamydia, gonorrhea, and prostate specific antigen (PSA) (to confirm lack of exposure to semen). Endocervical samples will be collected to measure immunological status. Blood will be collected to conduct hematology and liver and renal function testing, and plasma will be collected and stored for batch testing. Subjects will be provided with the investigational product or placebo, given a Daily Study Record, instructed how to use the product, complete the Daily Study Record, and report any adverse events (AEs). Follow-up visits will occur on Days 2, 7, 14, and 21. The primary study objective will be to determine the safety and tolerability of VivaGel™ applied vaginally twice daily for 14 days in HIV negative and STI-free young women. Safety assessments, comparing the VivaGel™ group to the placebo gel group, will include: incidence and severity of AEs, including genital tract signs and symptoms and mucosal changes as observed by colposcopy; vaginal microflora, including colonization with H2O2-producing lactobacilli; and laboratory parameters, including serum chemistry and hematology. The tolerability assessment, comparing the VivaGel™ group to the placebo gel group will include the proportion of participants who discontinued product use due to overt (i.e. observable) AEs, ascertained through a standardized questionnaire. The secondary objective of the study will be to report the effect of VivaGel™ applied vaginally twice daily for 14 days on the immune microenvironment in the lower genital tract of young women. Specifically, this will be tested by determining its effect on: the number and activation levels of endocervical immune cell populations; Secretory Leukocyte Protease Inhibitor (SLPI) levels; innate mucosal defenses, including local levels of cytokines in cervical secretions, and Toll-Like Receptor (TLR) expression by cervical immune cells; and the presence and expression levels of the HIV co-receptors CCR5 and CXCR4, and of their principal chemokine ligands by endocervical immune cells.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1: 3% w/w SPL7013 Gel | Experimental | Drug: 3% w/w SPL7013 Gel40 subjects VivaGel™. |
| 2: Placebo | Placebo comparator | Drug: Placebo20 subjects placebo. |
Who may qualify
- Ages
- 18 to 24 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Subject has voluntarily given written informed consent to participate in the study.
- Subject is female and aged between 18 and 24 years, inclusive.
- Subject is sexually active.
- Subject should have a menstrual cycle length of at least 25 days.
- Subject is in good health, as determined by medical history, a baseline physical examination, and clinical laboratory tests.
Key exclusion criteria (25 listed)
- Subject has received or is anticipated to receive a new prescription systemic or topical medication within 14 days prior to the start of dosing. Subjects may be enrolled if stable on existing therapy as determined by the Principal Investigator.
- Subject has received any new long-acting treatments [e.g. depot formulation including medroxyprogesterone acetate (DMPA) form of hormonal birth control]. Subjects may be enrolled if stable (greater than 3 months) on existing therapy as determined by the Principal Investigator.
- Subject has received an investigational drug within 30 days or 10 half-lives of the drug, whichever is longer, prior to entering this study, or is planning to receive another investigational drug while participating in this study.
- Subject has a history of significant drug allergy.
- Subject has a history of latex allergy.
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 |
|---|---|---|
| 3% w/w SPL7013 GelTwice-daily vaginal application of 3.5 g of VivaGel™ (Carbopol®-based gel with 3% w/w SPL7013) in single use pre-filled applicators. | Drug | 1: 3% w/w SPL7013 Gel |
| PlaceboPlacebo gel (Carbopol®-based formulation alone) in single use pre-filled applicators. | Drug | 2: Placebo |
Primary outcome
Tolerability will assess the degree to which overt Adverse Events can be tolerated by the study participants.
Time frame: Tolerability measures will be assessed at Days 2, 7, and 14 visits.
Safety will be assessed by laboratory tests and clinical Adverse Events.
Time frame: Safety assessed after 2, 7, and 14 days of product use and 7 days following the completion of product use (Day 21).
4 secondary outcomes
Presence and expression levels of Human Immunodeficiency Virus co-receptors CCR5 and CXCR4, and their principal chemokine ligands by endocervical immune cells.
Time frame: Immunologic factors of the genital tract will be measured using cervicovaginal specimens collected at enrollment, Day 7, Day 14, and Day 21.
Secretory Leukocyte Protease Inhibitor levels.
Time frame: Immunologic factors of the genital tract will be measured using cervicovaginal specimens collected at enrollment, Day 7, Day 14, and Day 21.
Number and activation levels of endocervical immune cell populations.
Time frame: Immunologic factors of the genital tract will be measured using cervicovaginal specimens collected at enrollment, Day 7, Day 14, and Day 21.
Innate mucosal defenses, including local levels of cytokines in cervical secretions, and Toll-Like Receptor expression by cervical immune cells.
Time frame: Immunologic factors of the genital tract will be measured using cervicovaginal specimens collected at enrollment, Day 7, Day 14, and Day 21.
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 23 Aug 2013.
- Results publication: PubMed 21311578Cohen CR, Brown J, Moscicki AB, Bukusi EA, Paull JR, Price CF, Shiboski S. A phase I randomized placebo controlled trial of the safety of 3% SPL7013 Gel (VivaGel(R)) in healthy young women administered twice daily for 14 days. PLoS One. 2011 Jan 20;6(1):e16258. doi: 10.1371/journal.pone.0016258.
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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 3% w/w SPL7013 Gel in people with Herpes Simplex II, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 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 9 inclusion and 25 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 23 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Kenya. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Tolerability will assess the degree to which overt Adverse Events can be tolerated by the study participants. (time frame: Tolerability measures will be assessed at Days 2, 7, and 14 visits.). 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 NCT00331032, which also lists 1 linked publication.
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 23 Aug 2013.