Flo Digital Contraceptive Study

Flo Health Inc.3,800 enrolled

Overview

The goal of this clinical trial is to learn if the Flo Digital Contraceptive (FDC) app can effectively prevent unintended pregnancy in women aged 18 years and older residing in the United States. The main questions it aims to answer are: What is the rate of unintended pregnancy in women aged 18-35 years using FDC as their sole method of contraception under typical-use conditions, measured using the Pearl Index? What is the cumulative probability of unintended pregnancy over 13 menstrual cycles for all participants, including those with regular and irregular cycles? Participants will: Use the Flo Digital Contraceptive app in 'prevent pregnancy' mode as their primary method of contraception for up to 13 menstrual cycles or 18 months, whichever comes first Wear an Apple Watch (Series 8 or later, or Ultra) while sleeping to collect nightly wrist temperature data, which the app uses to detect ovulation Log menstrual cycles, sexual activity, and any use of emergency contraception directly in the Flo app Complete monthly electronic surveys (ePROs) administered by the study team covering pregnancy status, adherence, safety, and experience Complete a baseline demographic survey at enrollment and an exit survey at the end of participation

Study Overview The FOCUS trial (Flo Contraceptive US Study) is a prospective, single-arm, non-randomized, decentralized clinical study evaluating the contraceptive safety and effectiveness of the Flo Digital Contraceptive (FDC) - a fertility awareness-based Software as a Medical Device (SaMD) - in preventing unintended pregnancy. The study is sponsored by Flo Health Inc. and conducted by Lindus Health Ltd. as the Contract Research Organization (CRO), with participant recruitment across the United States. The FDC is a proprietary machine-learning algorithm integrated within the Flo Period \& Cycles Tracker app (iOS). It uses menstrual cycle history and physiological indicators of ovulation - primarily overnight wrist-skin temperature measured via Apple Watch (Series 8 or later, or Ultra), with optional urinary luteinizing hormone (LH) tests - to dynamically classify each day of the user's cycle as either 'Not fertile' (unprotected intercourse permitted) or 'Use protection' (abstinence or barrier contraception required). The FDC operates as an API-based SaMD integrated within the Flo app as the target user interface. The algorithm predicts daily fertility based on user-provided inputs, with predictions dynamically updated as new data is received. Wrist-skin temperature is continuously monitored throughout sleep, which accommodates variable sleep schedules and is a reliable method for detecting biphasic temperature patterns associated with ovulation. For participants with irregular cycles, the FDC algorithm adaptively expands the 'Use protection' window in proportion to detected cycle length variability. Following enrollment confirmation and FDC device activation, participants log menstrual period dates, sexual activity (including whether barrier methods were used), and any use of emergency contraception in the Flo app. Participants are followed for up to 13 menstrual cycles or 18 months from device activation, whichever occurs first. Study Objectives The primary objective is to evaluate the typical-use contraceptive effectiveness of FDC in preventing unintended pregnancy among women aged 18-35 years with regular menstrual cycles (21-35 days), using the Pearl Index assessed against a pre-specified clinically acceptable upper limit of 10 pregnancies per 100 woman-years. A supporting secondary analysis uses Kaplan-Meier life-table methodology to estimate cumulative pregnancy probability over 13 cycles for all participants, assessed against a pre-specified cumulative threshold of less than 10%. Participants will be censored from the life-table analysis for voluntary withdrawal, loss to follow-up, study completion, or ineligibility. Secondary objectives will evaluate perfect-use effectiveness of FDC in the highest-risk population (aged 18-35 years), and typical-use and perfect-use effectiveness of FDC in the full intended-use population (aged 18 years and older), using the same statistical approaches. Exploratory objectives will evaluate typical-use effectiveness across pre-specified subgroups: cycle regularity (regular vs. irregular), Flo user status at enrollment (existing vs. new), and recency of hormonal contraceptive discontinuation (within vs. beyond 3 months prior to enrollment). Sample size Target enrollment is 3,800 participants, determined by the more conservative of two sample size calculations. The Pearl Index analysis requires approximately 900 participants (568 woman-years of exposure), while the Kaplan-Meier analysis requires 3,800 participants to achieve 80% power. A per-cycle dropout rate of 8% is assumed, corresponding to approximately 66% cumulative attrition by cycle 13. Safety Monitoring Given that FDC is a SaMD with no direct physiological interaction, the primary safety concern in this study is unintended pregnancy. This risk is monitored continuously through multiple safeguards including monthly pregnancy surveillance via ePRO and Flo app logging, participant-initiated reporting, and regular independent review by a Data Safety and Monitoring Board (DSMB). Regulatory and Ethical Oversight FOCUS is classified as a significant risk device study under 21 CFR Part 812. Enrollment will not commence until Institutional Review Board (IRB) approval has been obtained and FDA has granted IDE authorization. Informed consent is obtained electronically via Florence Healthcare in a fully asynchronous, documented process compliant with 21 CFR Part 11. Results will be publicly disclosed regardless of outcome in accordance with regulatory requirements and Good Publication Practice guidelines.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adults with female reproductive organs aged ≥18 years * Reside in the United States of America * Have menstrual frequency (i.e., interval between first day of bleeding each cycle) between 16-90 days * Sexually active, having vaginal sex with male partner(s) without known fertility problems AND where neither partner has a known, or is at high risk of, sexually transmitted infections (STIs). * Desiring contraception, i.e., planning to prevent pregnancy and not currently trying or planning to conceive for at least 12 months, and up to 18 months. from enrollment * Willing and able to use FDC as advised, including ability to: * (1) Abstain from penile-vaginal intercourse on days indicated as "Use protection" OR * (2) Use barrier methods (such as condoms) for penile-vaginal intercourse on days indicated as "Use protection" * Possession of an iOS mobile device (version 16 or higher) with internet connectivity * Sufficient English language proficiency and knowledge of English language required for correct use of the intervention and mobile device * Willing to wear a functional Apple Watch capable of sensing wrist-skin temperature (Series 8 or later, Ultra) while sleeping, with it connected and sharing temperature data to the Flo application * No known pregnancy at the time of enrollment * Willing and able to provide valid consent Exclusion Criteria: * Current use of any contraceptive medication, implant or technique, including but not limited to: * Oral contraceptive pills * Hormonal implants, injections, vaginal rings or transdermal patches * Intrauterine devices (copper and/or levonorgestrel) * Surgical sterilization (tubal ligation, salpingectomy, intrafallopian tube coils) * ≤12 weeks postpartum (second or third trimester pregnancy)\* * \*Includes terminations of any pregnancy \>14 weeks OR have given birth \>12 weeks postpartum without return of at least one menses * Postabortion (first trimester miscarriage, ectopic, termination) who have: * History of cycles outside the 21-35 day range, OR * Not had return of at least one menses following the abortion * Currently lactating (breastfeeding, pumping or otherwise), regardless of interval since last pregnancy * Had fewer than 9 menstrual cycles in the past 12 months * Have received medical advice from a healthcare provider that pregnancy is medically contraindicated, irrespective of whether this is due to a medical condition or risk, or due to medication being taken, or other reason. * Participants must be willing to NOT use condoms for penile-vaginal intercourse. Those who are unable or unwilling to restrict use of condoms for penile-vaginal intercourse for any reason, including but not limited to compromising health and/or safety of self or others will be excluded * Note: Use of barrier contraceptive for sexual encounters that could not result in pregnancy, such as oral or anal sex, is not restricted * Any condition or circumstance that, in the opinion of the Lead Investigator (LI) or designee, would compromise the participant's ability to comply with the study protocol, pose an unacceptable risk to the participant's safety or well-being, or interfere with the evaluation of study objectives * Concurrent participation in another research study that aims to prevent pregnancy * Extreme shift work patterns (e.g., unpredictable or rotating shifts changing more frequently than weekly, frequent time zone changes) that prevent consistent sleep schedules necessary for reliable temperature measurement

Outcomes

Primary Outcomes

Typical-Use Pearl Index in Women Aged 18-35 Years with Regular Menstrual Cycles

The Pearl Index (PI) is calculated as the number of unintended pregnancies per 100 woman-years of FDC exposure, assessed under typical-use conditions in women aged 18-35 years with regular menstrual cycles (21-35 days). An unintended pregnancy is defined as a documented positive pregnancy test occurring during active FDC use. Exposure time is calculated from the date of first FDC use (device activation) until confirmed pregnancy, intentional discontinuation, loss to follow-up, completion of 13 cycles, or study end, whichever occurs first. The PI is calculated with 95% exact Poisson confidence intervals. Effectiveness is concluded if the upper bound of the two-sided 95% CI is below the pre-specified clinically acceptable threshold of 10 pregnancies per 100 woman-years.