Clinical trial NCT03633799: Evaluation of Efficacy, Safety and Tolerability of VeraCept IUD
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Women at Risk for Pregnancy
Lead sponsor: Sebela Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: Synteract, Inc.
First posted: 2018-08-16
Enrollment: 1620
Sex: FEMALE
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: VeraCept Intrauterine Device (IUD)
Primary purpose: TREATMENT

Brief summary: To assess the contraceptive efficacy (prevention of pregnancy) of VeraCept

Detailed description: 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.

Eligibility criteria: 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 and has not had 2 normal menstrual cycles since the last injection;
7. Planned use of any non-contraceptive estrogen, progesterone or testosterone any time during 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.

Primary outcomes:
measure: contraceptive efficacy through 3 years of use
timeFrame: through 3 years of use
Secondary outcomes:
measure: Contraceptive efficacy at Years 4, 5, 6, 7 and 8
timeFrame: Years 4, 5, 6, 7, and 8 and cumulatively through Years 4, 5, 6, 7, and 8
measure: cumulative pregnancy percentage
timeFrame: Years 1 through 8
measure: Ease of VeraCept placement
timeFrame: Visit 1 (Day 1) / VeraCept placement
measure: VeraCept Placement success
timeFrame: Visit 1 (Day 1) / VeraCept placement
measure: Incidence of AEs and SAEs
timeFrame: 8 years
measure: Bleeding and spotting patterns
timeFrame: Through year 1
measure: Insertion pain assessed immediately after insertion
timeFrame: Visit 1 (Day 1), immediately after insertion
measure: Cumulative VeraCept continuation rates
timeFrame: Years 1 through 8
measure: Cumulative VeraCept expulsion rates
timeFrame: Years 1 through 8
measure: Return to Fertility. Only for subjects requesting VeraCept removal to become pregnant.
timeFrame: Subjects will be followed for either 1 year, until they decide to no longer try to conceive or they become pregnant, whichever comes first.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: MomDoc Women's Health Research
state: Arizona
city: Tucson
country: United States
facility: Copperstate OB/GYN Associates
state: Arizona
city: Berkeley
country: United States
facility: Essential Access Health
state: California
city: Los Angeles
country: United States
facility: Essential Access Health
state: California
city: Sacramento
country: United States
facility: University of California, Davis Health System
state: California
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: San Diego
country: United States
facility: Women's Health Care Research
state: California
city: Stanford
country: United States
facility: Stanford University, Medical Center, Obstetrics and Gynecolocy
state: California
city: Upland
country: United States
facility: Empire Clinical Research
state: California
city: Denver
country: United States
facility: Downtown Women's Health Care
state: Colorado
city: Lake Worth
country: United States
facility: Altus Research, Inc
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Decatur
country: United States
facility: Soapstone Center for Clinical Research
state: Georgia
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Fort Wayne
country: United States
facility: Women's Health Advantage
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Marrero
country: United States
facility: Praetorian Pharmaceutical Research
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Von Voigtlander Women's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota/Planned Parenthood
state: Minnesota
city: Manchester
country: United States
facility: Planned Parenthood of the St. Louis Region and Southwest Missouri
state: Missouri
city: Las Vegas
country: United States
facility: Rex Garn Mabey Jr., MD
state: Nevada
city: Lawrenceville
country: United States
facility: Lawrence OB/Gyn Clinical Research
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center, Division of Family Planning
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati/Reproductive Medicine Research
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Ob/Gyn Research Office
state: Ohio
city: Portland
country: United States
facility: OHSU Women's Health Research Unit
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania/Penn Family Planning and Pregnancy Loss Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Research of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital, Center for Family Planning Research
state: Pennsylvania
city: Charleston
country: United States
facility: Medical Research South, LLC
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Medical Research
state: Tennessee
city: Jackson
country: United States
facility: The Jackson Clinic, PA
state: Tennessee
city: Corpus Christi
country: United States
facility: Advanced Research Associates
state: Texas
city: Houston
country: United States
facility: Advances In Health
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Healthcare Health Sciences Center
state: Utah
city: Norfolk
country: United States
facility: Tidewater Physicians for Women
state: Virginia
city: Norfolk
country: United States
facility: Eastern Virginia Medical
state: Virginia
city: Seattle
country: United States
facility: Seattle Women's Health
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: University of Utah
name: David Turok, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: