HIVPhase 1VASTNCT02579083
Safety Study of Monoclonal Antibodies to Reduce the Vaginal Transmission of HSV and HIV
A Phase 1 study testing MB66 in people with HIV and Herpes Simplex Infections, run by KBio Inc at 1 site in United States.
Trial summary
The purpose of this study is to assess the safety and pharmacokinetics of MB66, a monoclonal antibody film for vaginal application that is being developed to potentially reduce the transmission of herpes simplex virus (HSV) and human immunodeficiency virus (HIV). 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, Herpes Simplex Infections
- What is being tested?
- MB66
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to Jul 2018
- 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
- 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
- In general good health as determined by the site clinician
- Agree to abstain from any vaginal insertions, including products, douches, devices such as sex toys, or penile or oral intercourse from 5 days prior to Visit 2 (Enrollment Visit) until the final Study Visit (one week after last dose of study film). Only tampons during menses and clinically indicated speculum exams are allowed.
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- Agree to use condoms provided by the study staff from one week after last use of study film until three weeks after last use of study film
- Willingness to undergo all study-related assessments and follow all study-related procedures
- Be currently using an effective method of contraception at enrollment (used continuously and with good compliance for the past 60 days as determined by participant self-report) with plans to continue use throughout the study period. Acceptable methods include any hormonal method (except vaginal ring); intrauterine device (IUD) inserted at least 90 days prior to enrollment; female sterilization; abstinent from sexual activity with male partner for the past 60 days; sexual activity with vasectomized partner; engages in sex exclusively with women.
- For participants 21 and older, 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 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, within the last 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
- Menopausal at screening (as defined as amenorrhea or irregular periods for one year or more without an alternative etiology)
- Hysterectomy
- Known adverse reaction to any of the study products (ever)
- Known adverse reaction to latex (ever)
- 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)
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- 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, a degree of menstrual cycle irregularity that would make it difficult to schedule follow up visits without interruption by menses
- Active sexually transmitted infection or documented treatment of sexually transmitted infections in the last 6 months, including, but not limited to: chlamydia, gonorrhea, syphilis, trichomonas, cervicitis or pelvic inflammatory disease, or currently active HSV lesions or other sores. (Participants seropositive for or with a history of HSV without current active lesions will not be excluded.)
- Women who by history engage in condom-less intercourse with HIV-infected partners, or who exchange sex for money, shelter, or gifts, or who in the opinion of the investigators, may be at risk for HIV acquisition during the duration of the study
- More than one sex partner within the past 3 months
- Current sexual partner known by participant to be HIV seropositive
- Current or planned use of pre-exposure prophylaxis against HIV infection
- Currently active genital HSV lesions, or other genital tract epithelial disruption or inflammation
- Current or episodic use of anti-herpes suppressive therapy
- Urinary tract infection, symptomatic candidiasis, or symptomatic bacterial vaginosis within 14 days of enrollment, or currently residual symptoms thereof Note: women with these infections at screening can be enrolled after treatment and resolution of the infection.
- Antibiotic or antifungal therapy (vaginal or systemic) within 7 days of enrollment
- Use of systemic immunomodulatory medications within 4 weeks of enrollment
- Menses or other vaginal bleeding at the time of enrollment* or expecting menses in the 10 days after enrollment (Segment A participants) or 16 days after enrollment (for Segment B participants)
- 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.
- Lack of stable living conditions to allow reliable room temperature storage of study product (Segment B participants only)
- At enrollment has any of the following laboratory abnormalities per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, Nov 2014:
- Grade 1 or higher AST (aspartate aminotransferase) or ALT (alanine aminotransferase)
- Grade 1 or higher creatinine
- Grade 2 or higher hemoglobin
- Grade 1 or higher platelets Note: otherwise eligible participants with an exclusionary test may be re-tested once during the screening process.
- As determined by the Principal Investigator (PI), any subject who has any significant uncontrolled active or chronic cardiovascular, renal, liver, hematologic, neurologic, gastrointestinal, psychiatric, endocrine, respiratory, immunologic disorder or infectious disease, anticoagulation with warfarin or heparin; or any other 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.
About this study
Official title: A Phase 1, Single Center Study to Assess the Safety of MB66, a Combined Anti-HIV (VRC01-N) and Anti-HSV (HSV8-N) Monoclonal Antibody Film for Vaginal Application as Microbicide
The purpose of this study is to assess the safety and pharmacokinetics of MB66, a monoclonal antibody film for vaginal application that is being developed to potentially reduce the transmission of herpes simplex virus (HSV) and human immunodeficiency virus (HIV).
Read the detailed description
This is a single center, Phase 1, randomized, single blind, placebo-controlled, two-segment study to assess the safety of the MB66 vaginal film. After appropriate screening, approximately 43 healthy women will be enrolled. The study will be divided into two sequential Segments. The first, Segment A, is a single-arm, single-dose, open label design. The 8 Segment A participants will receive a single dose of one full MB66 film. After dosing, subjects will be asked to maintain sexual abstinence and will be evaluated in person on Day 1 (24-hours post MB66 administration), by telephone on Day 3 or 4 and in person on the Day 6-10 Exit Visit, after which subjects will be allowed to resume sexual activity with study-provided condoms until three weeks after last exposure to film (to avoid male exposure to residual drug product). A placebo arm is not included in Segment A, because the very low risk of toxicity of the placebo film makes it unlikely that any toxicity observed in Segment A would be wrongly attributed to the active agents (mAbs) in the MB66 film. This conclusion is based on the known tolerance of the very similar vehicle used in a commercial polyvinyl alcohol (PVA)-based vaginal film (VCF®), and the absence of toxicity of the MB66 placebo film in the very sensitive rabbit model after substantially higher dosing intensity and duration.
Completion of Segment A and a safety review of Segment A adverse events will trigger the initiation of Segment B, a repeat dose, randomized, two arm, single-blind, placebo-controlled design. Subjects will be randomized 1:1 into two groups (15 evaluable subjects per group) and be treated once daily with either 1 MB66 film or 1 vehicle control placebo film for seven consecutive days. For five days before, and for 7 days after the dosing period, subjects will be asked to maintain a period of sexual abstinence. Subjects will be evaluated in person on Day 0 (at 1 and 4 hours post MB66 in-clinic dosing), again on Day 1 (24 hr post dosing), by telephone on Day 3-4, and evaluated again in person on Day 7-8, after which, subjects will be allowed to resumed sexual activity with condoms required until three weeks after last film insertion. Subjects will be evaluated a last time on the Day 12-16 Exit Visit.
In addition to safety measures, pharmacokinetic evaluations will be done on Day 0, Day 1, and Day 7 in both Segments, and additionally on Day 14 for Segment B. Specifically, this study will evaluate the rate of MB66 film dissolution, the vaginal concentrations of the MB66 antibodies, and the degree of systemic absorption of the MB66 antibodies. A number of of exploratory objectives will also be evaluated, including assessment of the antiviral effect of the MB66 antibodies ex vivo in cervicovaginal lavage fluid from participants after dosing with MB66 film, the effects of MB66 and placebo films on the cervicovaginal microbial environment using pH, Nugent score, and bacterial ribosomal DNA polymerase chain reaction (PCR), and comparison of the effect of MB66 and placebo films on cervicovaginal immune mediators by Luminex and ELISA assays. Segment B participants will also be asked to assess the acceptability of the MB66 vaginal film after 7 days of use.
- Conditions
- HIV, Herpes Simplex Infections
- Being tested
- MB66, Placebo Film
- Medical subject headings
- Herpes Simplex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MB66Drug
Also called Investigational Product
10 mg of HSV8-N and 10 mg of VRC01-N monoclonal antibodies per MB66 film
Placebo FilmDrug
Also called Placebo
The placebo film is composed of the identical excipients as MB66 without the monoclonal antibodies.
| Study group | Role | What they receive |
|---|---|---|
| Segment A: Single MB66 Administration | Experimental | 10 mg of HSV8-N and 10 mg of VRC01-N monoclonal antibodies per MB66 film Receives: Drug: MB66 |
| Segment B: Repeated Administrations Placebo Film | Placebo comparator | The placebo film is composed of the identical excipients as MB66 without the monoclonal antibodies. Receives: Drug: Placebo Film |
| Segment B: Repeated Administrations MB66 | Experimental | 10 mg of HSV8-N and 10 mg of VRC01-N monoclonal antibodies per MB66 film Receives: Drug: MB66 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Grade 2 or higher Adverse Events deemed related to study product
Grade 2 or higher Adverse Events
Measured: Segment A, cumulative events to Day 7; Segment B, cumulative events to Day 10
Secondary outcomes (3)
Naked eye visual assessment during speculum exam of the degree of film dissolution
visual assessment during speculum exam
Measured: 1, 4, and 24 hours after dosing
Concentrations of MB66 antibodies in vaginal fluid sampled with Tear Flo (filter paper) wicks, and measured by enzyme linked immunosorbent assay (ELISA)
Concentrations of MB66 antibodies in vaginal fluid
Measured: Pre-dose, 1 hr and 4 hr post dose, day 1, day 6-10 and day 12-16 (Segment B only)
Concentrations of MB66 antibodies in serum by ELISA
Concentrations of MB66 antibodies in serum
Measured: Screening visit, day 1, day 6-10 and day 12-16 (segment B only)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2015 (estimated)
- Study startJan 2016
- Primary completionJul 2018
- Study completionJul 2018
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- KBio Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Boston University, The Miriam Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02579083
- Sponsor's protocol ID
- MB66-01
- Other IDs
- U19AI096398
- Acronym
- VAST
- Status last verified
- Nov 2023
- First submitted
- 9 Oct 2015
- Last updated
- 14 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Politch JA, Cu-Uvin S, Moench TR, Tashima KT, Marathe JG, Guthrie KM, Cabral H, Nyhuis T, Brennan M, Zeitlin L, Spiegel HML, Mayer KH, Whaley KJ, Anderson DJ. Safety, acceptability, and pharmacokinetics of a monoclonal antibody-based vaginal multipurpose prevention film (MB66): A Phase I randomized trial. PLoS Med. 2021 Feb 3;18(2):e1003495. doi: 10.1371/journal.pmed.1003495. eCollection 2021 Feb.
PubMed 33534791
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Single Center Study to Assess the Safety of MB66, a Combined Anti-HIV (VRC01-N) and Anti-HSV (HSV8-N) Monoclonal Antibody Film for Vaginal Application as Microbicide
- ClinicalTrials.gov ID
- NCT02579083
- Acronym / sponsor ID
- VAST / MB66-01
- Conditions
- HIV, Herpes Simplex Infections
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- KBio IncIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Boston University, The Miriam Hospital
- Study start
- Jan 2016
- Primary completion
- Jul 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 19 Oct 2015 (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 assess the safety and pharmacokinetics of MB66, a monoclonal antibody film for vaginal application that is being developed to potentially reduce the transmission of herpes simplex virus (HSV) and human immunodeficiency virus (HIV).
Detailed description
This is a single center, Phase 1, randomized, single blind, placebo-controlled, two-segment study to assess the safety of the MB66 vaginal film. After appropriate screening, approximately 43 healthy women will be enrolled. The study will be divided into two sequential Segments. The first, Segment A, is a single-arm, single-dose, open label design. The 8 Segment A participants will receive a single dose of one full MB66 film. After dosing, subjects will be asked to maintain sexual abstinence and will be evaluated in person on Day 1 (24-hours post MB66 administration), by telephone on Day 3 or 4 and in person on the Day 6-10 Exit Visit, after which subjects will be allowed to resume sexual activity with study-provided condoms until three weeks after last exposure to film (to avoid male exposure to residual drug product). A placebo arm is not included in Segment A, because the very low risk of toxicity of the placebo film makes it unlikely that any toxicity observed in Segment A would be wrongly attributed to the active agents (mAbs) in the MB66 film. This conclusion is based on the known tolerance of the very similar vehicle used in a commercial polyvinyl alcohol (PVA)-based vaginal film (VCF®), and the absence of toxicity of the MB66 placebo film in the very sensitive rabbit model after substantially higher dosing intensity and duration.
Completion of Segment A and a safety review of Segment A adverse events will trigger the initiation of Segment B, a repeat dose, randomized, two arm, single-blind, placebo-controlled design. Subjects will be randomized 1:1 into two groups (15 evaluable subjects per group) and be treated once daily with either 1 MB66 film or 1 vehicle control placebo film for seven consecutive days. For five days before, and for 7 days after the dosing period, subjects will be asked to maintain a period of sexual abstinence. Subjects will be evaluated in person on Day 0 (at 1 and 4 hours post MB66 in-clinic dosing), again on Day 1 (24 hr post dosing), by telephone on Day 3-4, and evaluated again in person on Day 7-8, after which, subjects will be allowed to resumed sexual activity with condoms required until three weeks after last film insertion. Subjects will be evaluated a last time on the Day 12-16 Exit Visit.
In addition to safety measures, pharmacokinetic evaluations will be done on Day 0, Day 1, and Day 7 in both Segments, and additionally on Day 14 for Segment B. Specifically, this study will evaluate the rate of MB66 film dissolution, the vaginal concentrations of the MB66 antibodies, and the degree of systemic absorption of the MB66 antibodies. A number of of exploratory objectives will also be evaluated, including assessment of the antiviral effect of the MB66 antibodies ex vivo in cervicovaginal lavage fluid from participants after dosing with MB66 film, the effects of MB66 and placebo films on the cervicovaginal microbial environment using pH, Nugent score, and bacterial ribosomal DNA polymerase chain reaction (PCR), and comparison of the effect of MB66 and placebo films on cervicovaginal immune mediators by Luminex and ELISA assays. Segment B participants will also be asked to assess the acceptability of the MB66 vaginal film after 7 days of use.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Segment A: Single MB66 Administration | Experimental | Drug: MB6610 mg of HSV8-N and 10 mg of VRC01-N monoclonal antibodies per MB66 film |
| Segment B: Repeated Administrations Placebo Film | Placebo comparator | Drug: Placebo FilmThe placebo film is composed of the identical excipients as MB66 without the monoclonal antibodies. |
| Segment B: Repeated Administrations MB66 | Experimental | Drug: MB6610 mg of HSV8-N and 10 mg of VRC01-N monoclonal antibodies per MB66 film |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 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
- In general good health as determined by the site clinician
Key exclusion criteria (30 listed)
- Menopausal at screening (as defined as amenorrhea or irregular periods for one year or more without an alternative etiology)
- Hysterectomy
- Known adverse reaction to any of the study products (ever)
- Known adverse reaction to latex (ever)
- Non-therapeutic injection drug use in the 12 months prior to screening
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 |
|---|---|---|
| MB66Also: Investigational Product10 mg of HSV8-N and 10 mg of VRC01-N monoclonal antibodies per MB66 film | Drug | Segment A: Single MB66 Administration, Segment B: Repeated Administrations MB66 |
| Placebo FilmAlso: PlaceboThe placebo film is composed of the identical excipients as MB66 without the monoclonal antibodies. | Drug | Segment B: Repeated Administrations Placebo Film |
Primary outcome
Incidence of Grade 2 or higher Adverse Events deemed related to study product
Time frame: Segment A, cumulative events to Day 7; Segment B, cumulative events to Day 10
Grade 2 or higher Adverse Events
3 secondary outcomes
Naked eye visual assessment during speculum exam of the degree of film dissolution
Time frame: 1, 4, and 24 hours after dosing
Concentrations of MB66 antibodies in vaginal fluid sampled with Tear Flo (filter paper) wicks, and measured by enzyme linked immunosorbent assay (ELISA)
Time frame: Pre-dose, 1 hr and 4 hr post dose, day 1, day 6-10 and day 12-16 (Segment B only)
Concentrations of MB66 antibodies in serum by ELISA
Time frame: Screening visit, day 1, day 6-10 and day 12-16 (segment B only)
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 14 Nov 2023.
- Derived from this study: PubMed 33534791Politch JA, Cu-Uvin S, Moench TR, Tashima KT, Marathe JG, Guthrie KM, Cabral H, Nyhuis T, Brennan M, Zeitlin L, Spiegel HML, Mayer KH, Whaley KJ, Anderson DJ. Safety, acceptability, and pharmacokinetics of a monoclonal antibody-based vaginal multipurpose prevention film (MB66): A Phase I randomized trial. PLoS Med. 2021 Feb 3;18(2):e1003495. doi: 10.1371/journal.pmed.1003495. eCollection 2021 Feb.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 MB66 in people with HIV and Herpes Simplex Infections, run by KBio Inc 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 11 inclusion and 30 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 14 Nov 2023. 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?
Incidence of Grade 2 or higher Adverse Events deemed related to study product (time frame: Segment A, cumulative events to Day 7; Segment B, cumulative events to Day 10). 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 NCT02579083, 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 14 Nov 2023.