HIVPhase 1FAME 04NCT01989663
A Phase I Trial to Assess the Safety of Tenofovir Gel and Film Formulations: FAME 04
A Phase 1 study testing 1% vaginally applied tenofovir gel, Tenofovir film- 10mg and Tenofovir Film-40 mg in people with HIV, run by CONRAD at 1 site in United States.
Trial summary
This is a Phase I, five arm, single site, randomized, double blind placebo-controlled trial assessing the safety of tenofovir vaginal gel and film formulations. HIV negative women will be randomized to gel or film, tenofovir or placebo. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV
- What is being tested?
- 1% vaginally applied tenofovir gel, Tenofovir film- 10mg and Tenofovir Film-40 mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2013to Jan 2015
- 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 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women must meet all of the following criteria to be eligible for inclusion in the study:
- Age 18 through 45 years (inclusive) at screening
- Able and willing to provide written informed consent to be screened for and enrolled in the study.
- Able and willing to provide adequate locator information at screening.
- HIV-uninfected based on testing performed by study staff at screening (per algorithm in Appendices I)
- In general good health as determined by the site clinician
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- Agree to abstain from any intravaginal or rectal product or device or penetration (including vaginal, anal, or oral sex, masturbation, or sex toys) from 7 days prior to Visit 2 (Enrollment Visit) until 7 days after the completion of Visit 3. Only tampons and clinically indicated speculum exams are excluded.
- Agree to use study condoms between Visits 3 and 4 (if heterosexually active)
- Willingness to undergo all study-related assessments and follow all study-related procedures
- Per participant report, using an effective method of contraception at enrollment; hormonal method (except vaginal ring) used continuously for the past 30 days; intrauterine device (IUD inserted at least 90 days prior to enrollment); female sterilization; abstinent from sexual activity with male partner for the past 30 days; or sexual activity with vasectomized partner; and willingness to use effective method of contraception until the completion of final scheduled study visit if enrolled (approximately 35 days after enrollment)
- For participants older than 21, a pap result in the 36 calendar months prior to the Enrollment Visit consistent with Grade 0 according to the Female Genital Grading Table for Use in Microbicide Studies Addendum 1 to the DAIDS Table for Grading Adult and Pediatric Adverse Events, Version 0.1, December 2004 (Clarification dated August 2009) or satisfactory evaluation with no treatment required of non-Grade 0 Pap result per American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines or per local standard of care, in the 36 calendar months prior to enrollment.
- Note: For participants aged 18-21, a Grade-0 or adequately evaluated abnormal Pap smear is not required as the American Society for Colposcopy and Cervical Pathology recommends initiating screening at age 21.
- At screening and enrollment, agrees not to participate in other research studies involving drugs, medical devices, or vaginal products while enrolled in this trial
Who cannot join
- Women who meet any of the following criteria by participant report will be excluded from the study. Of note, the study is limited to premenopausal women with an intact uterus because the mucosal immune environment differs substantially between pre- and post- menopausal women. Therefore, inclusion of post-menopausal women would introduce heterogeneity into the population.
- Menopausal at screening (as defined as amenorrhea for one year or more without an alternative etiology)
- Hysterectomy
- Participant report of any of the following at screening:
- Known adverse reaction to any of the study products (ever)
- Known adverse reaction to latex (ever)
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- Non- therapeutic injection drug use in the 12 months prior to screening
- Surgical procedure involving the pelvis in the 90 days prior to screening (includes dilation and curettage or evacuation, and cryosurgery; does not include cervical biopsy for evaluation of an abnormal pap smear or IUD placement)
- Participation in a drug, spermicide and/or microbicide study in the 30 days prior to screening or anticipated participation in an investigational drug study in the next 8 weeks
- Pregnancy within 90 days prior to screening
- Lactating
- Use of a diaphragm, NuvaRing®, or spermicide for contraception
- As determined by the PI, has any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease
- Urogenital infection or suspected infection within 14 days of enrollment including: symptomatic candidiasis, trichomonas vaginalis, and symptomatic bacterial vaginosis; or cervical infection, including Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), or mucopurulent cervicitis; syphilis; HSV lesions, or other sores (Note: participants seropositive for HSV without active lesions will not be excluded); acute pelvic inflammatory disease; urinary tract infection
- Antibiotic or antifungal therapy (vaginal or systemic) within 7 days of enrollment
- Menses or other vaginal bleeding at the time of enrollment* or expecting menses in the 10 days after enrollment.
- Note, for women with monthly cycles, every attempt will be made to enroll these participants in the first half of their menstrual cycle. Women who have vaginal bleeding at the scheduled Enrollment Visit may return at a different date to be re-examined and possibly enrolled provided they are still within the screening window and meet all criteria.)
- At enrollment has any of the following laboratory abnormalities per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 0.1 December 2004:
- Grade 1 or higher AST or ALT
- Grade 1 or higher creatinine
- Grade 2 or higher hemoglobin
- Grade 1 or higher platelets
- Positive for HBsAg test result (Note: otherwise eligible participants with an exclusionary test may be re-tested once during the screening process ).
- Any condition that, in the opinion of the Investigator, would preclude provision of consent, make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
Trial locations and contacts
1 site in 1 country.
United States1 site
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
About this study
This is a Phase I, five arm, single site, randomized, double blind placebo-controlled trial assessing the safety of tenofovir vaginal gel and film formulations. HIV negative women will be randomized to gel or film, tenofovir or placebo. This study will provide additional information in the evaluation of vaginal films containing microbial agents in humans. In addition to safety, the efficacy of these formulations against HIV in an ex vivo biopsy challenge model will be compared.
This study is the first study assessing the safety of tenofovir film in humans. Tenofovir film is formulated in a cellulose based vaginal film containing hydroxypropyl methyl cellulose (HPMC) E5 (5 cp), hydroxyethyl cellulose (HEC), Sodium Carboxymethylcellulose (NaCMC), and glycerin. The excipients of the film have documented safety in other clinical settings.
Read more
While the tenofovir film has not been studied extensively in preclinical studies, there are favorable safety data from the macaque study and a substantial body of research with tenofovir gel. It is appropriate to advance the tenofovir film products into a clinical trial for the following reasons:
- No safety concerns were note in the tenofovir film macaque trial.
- The toxicity of tenofovir administered vaginally has been studied extensively. No clinically significant toxicity associated with this route of administration has been observed to date.
- All of the active ingredients of the tenofovir film have been tested in pre-clinical toxicity studies; therefore, the influence of these ingredients on the toxicity profile of tenofovir has been adequately evaluated and has been shown to result in no local or systemic effects.
- The individual components of the tenofovir film have been adequately evaluated and have been shown to be safe.
- Conditions
- HIV
- Being tested
- 1% vaginally applied tenofovir gel, Tenofovir film- 10mg, Tenofovir Film-40 mg, HEC Placebo Gel, Placebo Vaginal Film
- Keywords
- Healthy Women
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1% vaginally applied tenofovir gelDrug
Tenofovir film- 10mgDrug
Tenofovir Film-40 mgDrug
HEC Placebo GelOther
Placebo Vaginal FilmOther
| Study group | Role | What they receive |
|---|---|---|
| 1% vaginally applied tenofovir gel | Experimental | 1% vaginally applied tenofovir gel administered for 7 daily doses Receives: Drug: 1% vaginally applied tenofovir gel |
| HEC placebo vaginal gel | Placebo comparator | HEC placebo vaginal gel administered for 7 daily doses Receives: Other: HEC Placebo Gel |
| Tenofovir film- 10mg | Experimental | Tenofovir Film 10mg inserted vaginally, administered for 7 daily doses Receives: Drug: Tenofovir film- 10mg |
| Tenofovir Film-40 mg | Experimental | Tenofovir Gel 40 mg inserted vaginally, administered for 7 daily doses Receives: Drug: Tenofovir Film-40 mg |
| Placebo Film | Placebo comparator | Placebo Film inserted vaginally, administered for 7 daily doses Receives: Other: Placebo Vaginal Film |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grade 2 or higher Adverse Events deemed related to study product
To assess the safety of gel and two film formulations of tenofovir
Measured: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Secondary outcomes (7)
Levels of glycoproteins and mucins measured in CVL samples
To compare the effects of gel and two film formulations of tenofovir on cervico-vaginal ecology
Measured: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Levels of tenofovir and its metabolite in CVL, genital tissue (one cervical and one vaginal biopsy), rectal fluid and vaginal fluid (as sampled by an absorptive material, such as sponge and/or wick)
Pharmacokinetic (PK):To compare the levels of tenofovir and its metabolite in the genital tissue, vaginal fluid (as sampled by absorptive material, such as sponge and/or wick), rectal fluid, cervicovaginal lavage, rectal fluid and plasma samples
Measured: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Quantitative vaginal cultures
To compare the effects of gel and two film formulations of tenofovir on cervico-vaginal ecology
Measured: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Nugent score
To compare the effects of gel and two film formulations of tenofovir on cervico-vaginal ecology
Measured: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Levels of anti-HIV-1, anti HSV and anti-bacterial activity in CVL
To compare the effects of gel and two film formulations of tenofovir on cervico-vaginal ecology
Measured: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Levels of cytokine and innate immunity factors in the genital compartment
To compare the effects of gel and two film formulations of tenofovir on cervico-vaginal ecology
Measured: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Levels of tenofovir and its metabolite in plasma
Pharmacokinetic (PK):To compare the levels of tenofovir and its metabolite in the genital tissue, vaginal fluid (as sampled by absorptive material, such as sponge and/or wick), rectal fluid, cervicovaginal lavage, rectal fluid and plasma samples
Measured: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2013 (estimated)
- Study startNov 2013
- Primary completionJan 2015
- Study completionJan 2015
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 HIVStudies 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 1
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- CONRAD
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Katherine Bunge, CONRAD
- Investigators
- Katherine Bunge, MD, Study chair, University of Pittsburgh-Magee Womens Hospital of UPMCSharon L Hillier, PhD, Study chair, University of Pittsburgh-Magee-Womens Hospital of UPMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01989663
- Sponsor's protocol ID
- PRO13080462
- Other IDs
- 1U19AI082639
- Acronym
- FAME 04
- Status last verified
- Jul 2016
- First submitted
- 5 Nov 2013
- Last updated
- 27 Jul 2016
- Results posted
- No
Publications
Bunge KE, Dezzutti CS, Hendrix CW, Marzinke MA, Spiegel HML, Moncla BJ, Schwartz JL, Meyn LA, Richardson-Harman N, Rohan LC, Hillier SL. FAME-04: A Phase 1 trial to assess the safety, acceptability, pharmacokinetics and pharmacodynamics of film and gel formulations of tenofovir. J Int AIDS Soc. 2018 Aug;21(8):e25156. doi: 10.1002/jia2.25156.
PubMed 30101439
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial to Assess the Safety of Tenofovir Gel and Film Formulations: FAME 04
- ClinicalTrials.gov ID
- NCT01989663
- Acronym / sponsor ID
- FAME 04 / PRO13080462
- Conditions
- HIV
- Keywords
- Healthy Women
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- CONRADUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)
- Study start
- Nov 2013
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 21 Nov 2013 (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.
This is a Phase I, five arm, single site, randomized, double blind placebo-controlled trial assessing the safety of tenofovir vaginal gel and film formulations. HIV negative women will be randomized to gel or film, tenofovir or placebo. This study will provide additional information in the evaluation of vaginal films containing microbial agents in humans. In addition to safety, the efficacy of these formulations against HIV in an ex vivo biopsy challenge model will be compared.
This study is the first study assessing the safety of tenofovir film in humans. Tenofovir film is formulated in a cellulose based vaginal film containing hydroxypropyl methyl cellulose (HPMC) E5 (5 cp), hydroxyethyl cellulose (HEC), Sodium Carboxymethylcellulose (NaCMC), and glycerin. The excipients of the film have documented safety in other clinical settings.
While the tenofovir film has not been studied extensively in preclinical studies, there are favorable safety data from the macaque study and a substantial body of research with tenofovir gel. It is appropriate to advance the tenofovir film products into a clinical trial for the following reasons:
- No safety concerns were note in the tenofovir film macaque trial.
- The toxicity of tenofovir administered vaginally has been studied extensively. No clinically significant toxicity associated with this route of administration has been observed to date.
- All of the active ingredients of the tenofovir film have been tested in pre-clinical toxicity studies; therefore, the influence of these ingredients on the toxicity profile of tenofovir has been adequately evaluated and has been shown to result in no local or systemic effects.
- The individual components of the tenofovir film have been adequately evaluated and have been shown to be safe.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1% vaginally applied tenofovir gel | Experimental | Drug: 1% vaginally applied tenofovir gel1% vaginally applied tenofovir gel administered for 7 daily doses |
| HEC placebo vaginal gel | Placebo comparator | Other: HEC Placebo GelHEC placebo vaginal gel administered for 7 daily doses |
| Tenofovir film- 10mg | Experimental | Drug: Tenofovir film- 10mgTenofovir Film 10mg inserted vaginally, administered for 7 daily doses |
| Tenofovir Film-40 mg | Experimental | Drug: Tenofovir Film-40 mgTenofovir Gel 40 mg inserted vaginally, administered for 7 daily doses |
| Placebo Film | Placebo comparator | Other: Placebo Vaginal FilmPlacebo Film inserted vaginally, administered for 7 daily doses |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Age 18 through 45 years (inclusive) at screening
- Able and willing to provide written informed consent to be screened for and enrolled in the study.
- Able and willing to provide adequate locator information at screening.
- HIV-uninfected based on testing performed by study staff at screening (per algorithm in Appendices I)
- In general good health as determined by the site clinician
Key exclusion criteria (24 listed)
- Women who meet any of the following criteria by participant report will be excluded from the study. Of note, the study is limited to premenopausal women with an intact uterus because the mucosal immune environment differs substantially between pre- and post- menopausal women. Therefore, inclusion of post-menopausal women would introduce heterogeneity into the population.
- Menopausal at screening (as defined as amenorrhea for one year or more without an alternative etiology)
- Hysterectomy
- Participant report of any of the following at screening:
- As determined by the PI, has any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease
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 |
|---|---|---|
| 1% vaginally applied tenofovir gel | Drug | 1% vaginally applied tenofovir gel |
| Tenofovir film- 10mg | Drug | Tenofovir film- 10mg |
| Tenofovir Film-40 mg | Drug | Tenofovir Film-40 mg |
| HEC Placebo Gel | Other | HEC placebo vaginal gel |
| Placebo Vaginal Film | Other | Placebo Film |
Primary outcome
Grade 2 or higher Adverse Events deemed related to study product
Time frame: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
To assess the safety of gel and two film formulations of tenofovir
7 secondary outcomes
Levels of glycoproteins and mucins measured in CVL samples
Time frame: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Levels of tenofovir and its metabolite in CVL, genital tissue (one cervical and one vaginal biopsy), rectal fluid and vaginal fluid (as sampled by an absorptive material, such as sponge and/or wick)
Time frame: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Quantitative vaginal cultures
Time frame: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Nugent score
Time frame: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Levels of anti-HIV-1, anti HSV and anti-bacterial activity in CVL
Time frame: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Levels of cytokine and innate immunity factors in the genital compartment
Time frame: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
Levels of tenofovir and its metabolite in plasma
Time frame: Specimens may be collected until the end of subject's participation in the study, approximately 35 days
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 27 Jul 2016.
- Derived from this study: PubMed 30101439Bunge KE, Dezzutti CS, Hendrix CW, Marzinke MA, Spiegel HML, Moncla BJ, Schwartz JL, Meyn LA, Richardson-Harman N, Rohan LC, Hillier SL. FAME-04: A Phase 1 trial to assess the safety, acceptability, pharmacokinetics and pharmacodynamics of film and gel formulations of tenofovir. J Int AIDS Soc. 2018 Aug;21(8):e25156. doi: 10.1002/jia2.25156.
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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.
Katherine Bunge, MD study chair
University of Pittsburgh-Magee Womens Hospital of UPMC
Sharon L Hillier, PhD study chair
University of Pittsburgh-Magee-Womens Hospital of UPMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 1% vaginally applied tenofovir gel, Tenofovir film- 10mg and Tenofovir Film-40 mg in people with HIV, run by CONRAD at 1 site in United States.
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 13 inclusion and 24 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 27 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Grade 2 or higher Adverse Events deemed related to study product (time frame: Specimens may be collected until the end of subject's participation in the study, approximately 35 days). 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 NCT01989663, 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 27 Jul 2016.