A Functional Performance Study of The Wondaleaf Female Condom
Condition: HIV Prevention; Pregnancy Prevention
Study type: Interventional

Summary: 
      This research study will determine how well two female condoms perform when used during sex.
      One of these condoms (FC2) is already commercially available in South Africa. The other
      female condom, "Wondaleaf Condom" is a new female condom. Participants will use both condoms.
      The study aims to determine how well these condoms work comparatively. Study visits include a
      screening/enrolment visit and 2 follow up visits.
    

Detailed description: 
      This research study will determine how well two female condoms perform when used during sex.
      One of these condoms (FC2) is already commercially available in South Africa. The other
      female condom, "Wondaleaf Condom" is a new female condom. Participants will use both condoms.
      The study aims to determine how well these condoms work comparatively.

      The Wondaleaf female condom is a new female condom (FC) design made of polyurethane with no
      external or internal rings. The body of the condom is fitted by an exterior adhesive shield
      which also displays the condom when removed from the condom packaging.

      Purpose: To ascertain the functional performance of the Wondaleaf FC. This research study
      will be a two-period, cross-over randomized controlled trial to compare the functional
      performance, safety and acceptability of two FC types.

      Study Design: The study will enrol 220 women, anticipating that 200 participants complete the
      study. The age range of these participants is from 18-45 years. Each participant will be
      asked to use five Wondaleaf FCs and five FC2 female condoms (available in the South African
      public sector).

      Primary endpoints will be total clinical failure and total device failure for each condom
      type. Secondary endpoints will include rates of invagination, complete slippage,
      misdirection, and breakage.

      Function, safety, and acceptability will be assessed at two follow-up visits approximately
      one month apart after enrollment. Participants will complete a Condom Log at home which
      gathers data on experience after use of each condom.

      Female clients of the Commercial City Clinic will be told about the study. If a potential
      participant expresses interest in participating, the participant will be given the study
      information to read, which will describe the study requirements and the potential role in the
      study. If the participant agrees to take part in the research, the participant will be asked
      to provide written consent. The participant will be screened to ensure that the requirements
      for study participation are met.

      Enrolled participants will be asked to use five FC2 and five Wondaleaf FCs. Participants will
      be asked to return to the clinic for follow-up after using each type of device. During the
      1st follow-up visit, participants will be interviewed about the first assigned condom type
      and will receive the next condom packet within their second assigned (randomized) use
      sequence. In the second follow-up visit, participants will be interviewed about use of the
      condoms and will be discontinued from study participation. Data on device function, safety
      and acceptability for each condom type will be collected during follow-up visits.

      At enrolment, baseline data will be gathered on participant demographics and past FC use via
      the baseline questionnaire. Using a pelvic model, the study staff will demonstrate female
      condom insertion and train the participants in the proper use of the first assigned female
      condom. Further, study staff will re- emphasize the instructions on how to complete the
      condom use log. Participants will be told that they do not have to use the FCs during
      consecutive acts of intercourse. The study staff will discuss with the participant an
      approximate timeframe for use of all 5 condoms and a suitable follow-up date will be
      scheduled. This date will be noted on an appointment slip. Participants will be encouraged to
      come back if condoms are finished before the due date and will be given the research study
      contact details to call for any appointment changes.

      Follow-up visits: There will be two follow-up visits. During the first follow-up visit, study
      staff will review the information on the Condom Use Logs for completeness and accuracy.
      Further, the participants will be asked questions from a follow-up survey about the
      experiences using the FCs. Participants will be trained in the use of the second condom type,
      and given appropriate written condom use instructions. Staff will schedule the second
      follow-up visit, and participants will obtain the next condom packet in the assigned use
      sequence. At the end of the second follow-up visit the discontinuation form will be
      completed. Participation period for study participants is expected to last between 2-4
      months.

      The study will be registered on the South African clinical trials registry (SANCTR) and on
      clinicaltrials.gov.

      The study will be monitored by an independent monitor contracted by the study investigator.
      The monitoring visit schedule includes an initiation visit, one interim visit and a close out
      visit. Risk based monitoring will be conducted for the study. The following study records
      will be reviewed:

        -  100% of informed consent forms

        -  100% of 100 enrolled participant files for source data verification

        -  100% of serious adverse events and protocol deviations

        -  Investigator site file

        -  Study product No audits are planned for the study. The study has employed data staff to
           complete daily quality control of documents to ensure accuracy and completeness of data
           and electronic case report forms.

      The site has Standard Operating Procedures in place to ensure consistency of site operations
      and study procedures. In addition, a source document guide and Manual of Procedures will be
      developed to ensure conformity.

      Statistical Considerations:

      The hypothesis for the primary endpoints, total clinical failure and total failure of a
      female condom and their components, is that the new condom WC2 is 'non-inferior' to FC2 with
      regard to the rate of events within a margin of 3.0%. That is, that the rate of events of
      each of the new condoms is not worse than that of the FC2 by more than 3.0%.

      To demonstrate non-inferiority at a 5% significance level, the study will require the upper
      limit of the one-sided 95% confidence interval or equivalently the upper limit of the
      two-sided 90% confidence interval for the difference in the occurrence of events (New - FC2)
      to be below 3.0%.

      It was calculated that the power to demonstrate non-inferiority obtained for different sample
      sizes, starting by the minimum of 200 couples completing the study recommended by ISO
      standards. It was assumed a total failure rate of 4% for the FC2 as reported from past
      research. It was assumed a correlation between uses of 0.15, as reported for male condoms.
      This assumption is more conservative than the maximum of 0.20 recommended by International
      Organization for Standardization (ISO) standards for female condoms.

      For acceptability, scores ranging from 1 (lowest) to 5 (highest) to be compared across condom
      types using Friedman test, the proposed sample size will provide more than 99% power to
      detect a minimum difference of 1 in the scores of any two condom types, in a 5% significance
      level two-sided test. This calculation assumes a standard error of 1 and adjusts for multiple
      inferences using Bonferroni criterion, but ignores clustering (condoms within couples).

      Data Analysis All analyses for primary and secondary endpoints will be performed according to
      the assigned condom use sequence among the subset of participants who provide relevant
      follow-up data on at least one condom of each type, no matter if they followed the assigned
      sequence. This will be the main analysis. An additional analysis will be performed with
      protocol compliers (i.e. participants who follow the assigned condom use sequence). All
      analyses for secondary endpoints will use a nominal 5% significance level.

      A detailed analysis plan will be developed prior to the initiation of study enrollment. Any
      deviations to be made from this summary will be documented in the detailed analysis plan.

      Condom Function The failure rates, or proportions of condom uses with clinical breakage,
      total breakage, slippage, misdirection, invagination, total clinical failure, and total FC
      failure will be summarized by condom type according to endpoint definitions. 95% confidence
      intervals for the proportion of each endpoint will be calculated using the exact method based
      on the binomial distribution.

      Safety Data The proportion of participants with symptoms of genitourinary irritation during
      or immediately after any of the 5 separate uses and medical and serious adverse events,
      classified by relatedness to condom type, expectedness and severity will be reported.

      Product Acceptability The key acceptability endpoints (listed below) will be summarized.

        -  comfort in use;

        -  ease of insertion and removal;

        -  like or dislike of product attributes and adequacy and feel of lubrication.
    

Intervention name(s): Wondaleaf Female Condom; FC2 Female Condom
Intervention type(s): Device; Device
Intervention description(s): Wondaleaf: Wondaleaf is an ultra thin (of 0.02 mm) polyurethane female/male condom (16x8cm) that has folded extended adhesive shields (front 18x18cm, back 18x10cm), which at unfolding covers the entire external genitalia to prevent direct skin contact and exchange of body fluid between sexual partners during intercourse. Insertion of the condom body into the vagina is through use of a small medical grade cotton tissue packed inside the foil package. This is inserted into the end of the condom body and used to push the condom into the vagina. Each condom is individually packaged without prior lubrication. However, lubricant is expected to be used at donning the condom and during sexual intercourse. The lubricant will be supplied in separate packets together with the condom. Unlike latex, polyurethane condoms are unlikely to cause any allergic reaction and are much stronger than conventional latex condoms; FC2: The FC2 is a second-generation female condom manufactured by the Female Health Company (Chicago, IL). The FC2 has US FDA approval and has been granted the CE Mark (Conformité Européenne) of the European Union. The FC2 is the only female condom that has been pre-qualified by the World Health Organisation. The device is similar in design to the FC1, but is made from a synthetic polymer (nitrile) film that is softer and more elastic than the polyurethane of the earlier device. The condom is designed as a loose-fitting pouch that lines the vagina. It has two flexible rings. The outer ring at the open end is rolled from the nitrile material. The outer ring remains outside the vagina and covers the external genitalia during intercourse. An internal polyurethane ring is removable and serves as the insertion mechanism and anchors the device within the vagina. FC2 measures 180mm in length and 80mm in lay-flat width. The device is pre-lubricated with dimethicone.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This research study will be a two-period, cross-over randomized controlled trial to compare the functional performance, safety and acceptability of two FC types (FC2 and Wondaleaf).
Masking: Single (Outcomes Assessor)
Primary purpose: Other
Keywords: female condom; HIV and STI prevention; Condom acceptability; Wondaleaf; FC2