Evaluation of Efficacy, Safety and Tolerability of VeraCept IUD

Study Design:

Prospective, multi-center, single-arm, open-label, Phase 3 clinical study to 3 years with
extension up to 5 years

Number of Subjects:

Approximately 1,605 subjects will be enrolled into the study

Study Population:

Post-menarcheal, pre-menopausal women up to age 45 years, who are at risk for pregnancy and
who desire a long-term intrauterine contraceptive for birth control will be eligible for this
study.

Primary Endpoint:

The primary endpoint is the contraceptive efficacy through 3 years of use, as assessed by the
Pearl Index.

Secondary endpoints:

Contraceptive Efficacy:

- Pearl Index at Years 4 and 5, as well as cumulatively through Years 4 and 5.

- Pregnancy percentage by life table analysis (Kaplan-Meier) at Years 1, 2, 3, 4 and 5

Study drug placement:

- Ease of VeraCept placement

- Placement success

Safety:

- Serious adverse events (SAEs)

- Adverse events (AEs)

- Pelvic infection (pelvic inflammatory disease (PID) or endometritis)

- Ectopic pregnancies

- Uterine perforations

- Dysmenorrhea

- Abdominal pain

- Expulsion rates at Years 1, 2, 3, 4 and 5

Tolerability:

- Bleeding and spotting patterns

- Insertion pain assessed immediately after insertion

- Continuation rates at Years 1, 2, 3, 4 and 5

- Reasons for discontinuation Return to fertility

- Pregnancy rate in subjects who request VeraCept removal specifically to become pregnant.
Subjects who desire pregnancy after having VeraCept removed will be followed for either
1 year, until they decide to no longer try to conceive or they become pregnant,
whichever comes first.

Inclusion Criteria:

1. Post-menarcheal, pre-menopausal females up to 45 years of age at the time of informed
consent/assent and in good general health;

2. History of regular menstrual cycles defined as occurring every 21-35 days when not
using hormones or prior to recent pregnancy or spontaneous or induced abortion;

3. Sexually active with a male partner who has not had a vasectomy;

4. Reasonably expect to have coitus at least once monthly during the study period;

5. In a mutually monogamous relationship of at least 3 months duration;

6. Seeking to avoid pregnancy for the duration of the study;

7. Willing to use the study drug as the sole form of contraception;

8. Willing to accept a risk of pregnancy;

9. Subjects who are age 21 or older, at time of informed consent, must have a normal
papanicolaou test (Pap) or atypical squamous cells of undetermined significance
(ASC-US) with negative high risk human papilloma virus (HPV) test result within the
appropriate screen timeframe per American Society for Colposcopy and Cervical
Pathology (ASCCP) guidelines, and prior to the study IUD insertion. Alternatively, the
subject must have had a colposcopy performed within the appropriate screen timeframe,
and prior to the study IUD insertion that showed no evidence of dysplasia requiring
treatment per ASCCP guidelines, or treatment was performed and follow-up at least 6
months after the treatment showed no evidence of disease by clinical evaluation;

10. Able and willing to comply with all study tests, procedures, assessment tools
(including e-diary) and follow-up;

11. Able and willing to provide and document informed consent and Authorization for
Release of Protected Health Information (PHI). Unemancipated subjects under 18 years
old must provide assent and have written parental consent documented on the consent
form consistent with local legal requirements;

12. Plan to reside within a reasonable driving distance of a research site for the
duration of the study.

13. Subject agrees not to self-remove VeraCept

Exclusion Criteria:

1. Known or suspected pregnancy; or at risk for pregnancy from unprotected intercourse
earlier in current cycle;

2. Subject who anticipates separation from her partner for more than a 6-month period
during use of VeraCept;

3. A previously inserted intrauterine device (IUD) that has not been removed by the time
the study IUD is placed;

4. History of previous IUD complications, such as perforation, expulsion, or pregnancy
with IUD in place;

5. Pain with current IUD;

6. Injection of hormonal contraceptive (e.g., Depo-Provera) within the last 10 months (if
injection greater than 3 months ago, must have had 2 normal menstrual cycles since the
last injection);

7. Planned use of any non-contraceptive estrogen, progesterone or testosterone any time
during the 60 months of study participation;

8. Exclusively breastfeeding before return of menses; lactating women will be excluded
unless they have had 2 normal menstrual periods prior to enrollment;

9. Unexplained abnormal uterine bleeding (suspicious for a serious condition), including
bleeding 4 weeks post-septic abortion or puerperal sepsis;

10. Severely heavy or painful menstrual bleeding;

11. Suspected or known cervical, uterine or ovarian cancer, or unresolved clinically
significant abnormal Pap smear requiring evaluation or treatment;

12. Any history of gestational trophoblastic disease with or without detectable elevated
ß-human chorionic gonadotropin (ß-hCG) levels, or related malignant disease;

13. Any congenital or acquired uterine anomaly that may complicate study drug placement,
such as:

- Submucosal uterine leiomyoma

- Asherman's syndromes

- Pedunculated polyps

- Bicornuate uterus

- Didelphus or uterine septa

14. Any distortions of the uterine cavity (e.g. fibroids), that, in the opinion of the
investigator, are likely to cause issues during insertion, retention or removal of the
IUD;

15. Known anatomical abnormalities of the cervix such as severe cervical stenosis, prior
trachelectomy or extensive conization that, in the opinion of the investigator would
prevent cervical dilation and study drug placement;

16. Untreated acute cervicitis or vaginitis within the past 3 months;

17. Known or suspected human immunodeficiency virus (HIV) infection or clinical AIDS;

18. Subjects who have an established immunodeficiency;

19. Known intolerance or allergy to any components of VeraCept including intolerance or
allergy to nickel, titanium, or copper, and including Wilson's Disease;

20. Currently participating or planning future participation in a research study of an
investigational drug or device during the course of this investigational study.
Subject must have waited at least 30 days from exiting their last study prior to
informed consent in this study;

21. Subject has been enrolled in a previous VeraCept study;

22. Known or suspected alcohol or drug abuse within 12 months prior to the screening
visit;

23. Any general health, mental health or behavioral condition that, in the opinion of the
investigator, could represent an increased risk for the subject or would render the
subject less likely to provide the needed study information;

24. Study staff or a member of the immediate family of study staff.