Evaluation of Efficacy, Safety and Tolerability of VeraCept IUD

Study Overview
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Brief Summary
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To assess the contraceptive efficacy (prevention of pregnancy) of VeraCept

Detailed Description
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Study Design: Prospective, multi-center, single-arm, open-label, Phase 3 clinical study to 3 years with extension up to 8 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, 5, 6, 7 and 8 as well as cumulatively through Years 4, 5, 6, 7 and 8. Pregnancy percentage by life table analysis (Kaplan-Meier) at Years 1, 2, 3, 4, 5, 6, 7 and 8 The cumulative Pearl Index for Years 6 to 8 will be calculated as well as the cumulative pregnancy percentage for Years 6 to 8 using a life table analysis (Kaplan-Meier) only for the EP population. 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, 5, 6, 7 and 8 Tolerability: Bleeding and spotting patterns Insertion pain assessed immediately after insertion Continuation rates at Years 1, 2, 3, 4, 5, 6, 7 and 8 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.

Official Title
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A Phase 3, Prospective, Multi-Center, Single-Arm, Open-Label Study to Evaluate VeraCept™, a Long-Acting Reversible Intrauterine Contraceptive for Contraceptive Efficacy, Safety, and Tolerability

Conditions
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Women at Risk for Pregnancy

Intervention / Treatment
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* Drug: VeraCept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-menarcheal, pre-menopausal females up to 45 years of age at the time of informed consent/assent and in good general health; 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; Sexually active with a male partner who has not had a vasectomy; Reasonably expect to have coitus at least once monthly during the study period; In a mutually monogamous relationship of at least 3 months duration; Seeking to avoid pregnancy for the duration of the study; Willing to use the study drug as the sole form of contraception; Willing to accept a risk of pregnancy; 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; Able and willing to comply with all study tests, procedures, assessment tools (including e-diary) and follow-up; 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; Plan to reside within a reasonable driving distance of a research site for the duration of the study. Subject agrees not to self-remove VeraCept Exclusion Criteria: Known or suspected pregnancy; or at risk for pregnancy from unprotected intercourse earlier in current cycle; Subject who anticipates separation from her partner for more than a 6-month period during use of VeraCept; A previously inserted intrauterine device (IUD) that has not been removed by the time the study IUD is placed; History of previous IUD complications, such as perforation, expulsion, or pregnancy with IUD in place; Pain with current IUD; Injection of hormonal contraceptive (e.g., Depo-Provera) within the last 10 months and has not had 2 normal menstrual cycles since the last injection; Planned use of any non-contraceptive estrogen, progesterone or testosterone any time during study participation; Exclusively breastfeeding before return of menses; lactating women will be excluded unless they have had 2 normal menstrual periods prior to enrollment; Unexplained abnormal uterine bleeding (suspicious for a serious condition), including bleeding 4 weeks post-septic abortion or puerperal sepsis; Severely heavy or painful menstrual bleeding; Suspected or known cervical, uterine or ovarian cancer, or unresolved clinically significant abnormal Pap smear requiring evaluation or treatment; Any history of gestational trophoblastic disease with or without detectable elevated ß-human chorionic gonadotropin (ß-hCG) levels, or related malignant disease; 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 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; 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; Untreated acute cervicitis or vaginitis within the past 3 months; Known or suspected human immunodeficiency virus (HIV) infection or clinical AIDS; Subjects who have an established immunodeficiency; Known intolerance or allergy to any components of VeraCept including intolerance or allergy to nickel, titanium, or copper, and including Wilson's Disease; 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; Subject has been enrolled in a previous VeraCept study; Known or suspected alcohol or drug abuse within 12 months prior to the screening visit; 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; Study staff or a member of the immediate family of study staff.

Ages Eligible for Study
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Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: VeraCept Intrauterine Device (IUD)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VeraCept<br>VeraCept™ Intrauterine Contraceptive | Drug: VeraCept<br>* VeraCept Intrauterine Contraceptive is a hormone free, low dose, copper-releasing birth control method<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| contraceptive efficacy through 3 years of use | contraceptive efficacy through 3 years of use, as assessed by the Pearl Index | through 3 years of use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Contraceptive efficacy at Years 4, 5, 6, 7 and 8 | Pearl Index will be calculated for Years 4, 5, 6, 7, and 8 as well as cumulatively through Years 4, 5, 6, 7, and 8 | Years 4, 5, 6, 7, and 8 and cumulatively through Years 4, 5, 6, 7, and 8 | 
| cumulative pregnancy percentage | A life table analysis (using Kaplan-Meier) of pregnancies will be performed for the EP population to present the cumulative pregnancy percentage for Years 1 through 8 | Years 1 through 8 | 
| Ease of VeraCept placement | Ease of VeraCept placement will be summarized for the Safety population as reported by the investigator (Very easy, Easy, Neither Easy nor Hard, Hard, Very Hard). | Visit 1 (Day 1) / VeraCept placement | 
| VeraCept Placement success | The number and percentage of subjects with either a successful or unsuccessful placement will be summarized for the ITT and Safety populations. | Visit 1 (Day 1) / VeraCept placement | 
| Incidence of AEs and SAEs | Incidence of AEs and SAEs will be summarized for the ITT population, as well as for the Safety population for all subjects and the 36 to 45-year-old safety sub-population. | 8 years | 
| Bleeding and spotting patterns | Bleeding and spotting patterns will be summarized for the ECYC population for the first year of treatment by the number of days in each 28-day cycle with bleeding or spotting, bleeding only and spotting only | Through year 1 | 
| Insertion pain assessed immediately after insertion | Summarized for subjects with and without prior prophylactic pain medication as measured by an 11-Point Numeric Pain Rating Scale. The scale being 0 - 10 with 0 being no pain and 10 being the worse pain | Visit 1 (Day 1), immediately after insertion | 
| Cumulative VeraCept continuation rates | Cumulative VeraCept continuation rates for Years 1 through 8 will be summarized using Kaplan-Meier methods for the Safety population. The number and percentage of subjects with each reason for discontinuation will be summarized. Continuation rates at Years 1, 2, 3, 4, 5, 6, 7 and 8 Reasons for discontinuation will be summarized. | Years 1 through 8 | 
| Cumulative VeraCept expulsion rates | Cumulative VeraCept expulsion rates for Years 1 through 8 will be summarized using Kaplan-Meier methods for the Safety population. | Years 1 through 8 | 
| Return to Fertility. Only for subjects requesting VeraCept removal to become pregnant. | The number and percentage of subjects with each return to fertility response will be summarized for the Safety population. | Subjects will be followed for either 1 year, until they decide to no longer try to conceive or they become pregnant, whichever comes first. |