Clinical trial NCT04457076: Evaluation of the Efficacy, Safety, and Tolerability of LevoCept
Official title: A Phase 3, Prospective, Multi-Center, Single-Arm, Open-Label Study to Evaluate LevoCept™, a Long-Acting Reversible Intrauterine System for Contraceptive Efficacy, Safety, and Tolerability
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Contraception
Women at Risk for Pregnancy
Keywords: Contraception
IUD
Lead sponsor: Sebela Pharmaceuticals Inc.
Sponsor class: INDUSTRY
Collaborators: name: PRA Health Sciences
First posted: 2020-07-07
Enrollment: 1525
Sex: FEMALE
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: LevoCept Intrauterine Device (IUD)
Primary purpose: TREATMENT

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

Detailed description: 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 1,525 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.

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 nor other known fertility problems;
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 at time of consent;
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 must be in compliance with cervical cancer screening guidelines per the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines without evidence of disease. Subjects who are age 21 to 24 y/o, at time of informed consent, must have a normal Papanicolaou test (Pap), atypical squamous cells of undetermined significance (ASC-US), or low-grade squamous intraepithelial lesion (LSIL). Subjects who are 25 or older at the time of informed consent must have a normal Pap test or an ASC-US result with a negative high-risk human papilloma virus (HPV) test result within the appropriate screen timeframe per 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/legal guardian consent documented on the consent form consistent with local legal requirements;
12. Plan to reside within a reasonable travel distance of a research site for the duration of the study.
13. Subject agrees not to intentionally self-remove LevoCept

Exclusion Criteria:

1. Known or suspected pregnancy; or at risk for pregnancy from unprotected intercourse earlier in current cycle;
2. Has had any procedure for or causing sterility (e.g. tubal ligation procedure);
3. Subject who anticipates separation from her partner for more than a 6-month period during use of LevoCept;
4. A previously inserted IUD/IUS that has not been removed by the time the study IUS is placed;
5. History of previous IUD/IUS complications, such as perforation, expulsion, or pregnancy with IUD/IUS in place;
6. Pain with current IUD/IUS;
7. 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;
8. Subject is \<4 weeks post-pregnancy (postpartum, spontaneous or induced abortion)
9. Planned use of any non-contraceptive estrogen, progesterone or testosterone any time during the 60 months of study participation;
10. Exclusively breastfeeding before return of menses; lactating women will be excluded unless they have had 2 normal menstrual periods prior to enrollment;
11. Unexplained abnormal uterine bleeding (suspicious for a serious condition), including bleeding 4 weeks post-septic abortion or puerperal sepsis;
12. Severely heavy or painful menstrual bleeding;
13. Suspected or known cervical, uterine or ovarian cancer, or unresolved clinically significant abnormal Pap test requiring evaluation or treatment;
14. Any history of gestational trophoblastic disease with or without detectable elevated ß-human chorionic gonadotropin (ß-hCG) levels, or related malignant disease;
15. 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
16. 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 IUS;
17. 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;
18. Untreated or unresolved acute cervicitis or vaginitis;
19. Known or suspected breast cancer or other progestin-sensitive cancer now or in the past;
20. Known acute liver disease or liver tumor;
21. Subjects who have an established immunodeficiency;
22. Known or suspected human immunodeficiency virus (HIV) infection or clinical AIDS;
23. At high risk for sexually transmitted infections (e.g. multiple sexual partners);
24. Known intolerance or allergy to any components of LevoCept, including intolerance or allergy to levonorgestrel, nickel, titanium, or silicone;
25. 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;
26. Subject has previously been enrolled in a VeraCept or LevoCept study (including the current study);
27. Known or suspected alcohol or drug abuse within 12 months prior to the screening visit;
28. 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;
29. Study staff or a member of the immediate family of study staff.

Primary outcomes:
measure: Contraceptive efficacy through 3 years of use as calculated by the Pearl Index
timeFrame: through 3 years of use
Secondary outcomes:
measure: Contraceptive efficacy at Years 4 and 5 as calculated by the Pearl Index
timeFrame: Years 4 and 5 and cumulatively through Years 4 and 5
measure: Pregnancy percentage
timeFrame: Years 1 through 5
measure: Ease of LevoCept placement
timeFrame: Day 1 / LevoCept placement
measure: LevoCept Placement success
timeFrame: Day 1 / LevoCept placement
measure: Incidence of AEs and SAEs
timeFrame: 5 years
measure: Bleeding and spotting patterns
timeFrame: Through year 1
measure: Insertion pain assessed immediately after insertion
timeFrame: Day 1, immediately after insertion
measure: Cumulative LevoCept continuation rates
timeFrame: Years 1 through 5
measure: Cumulative LevoCept expulsion rates
timeFrame: Years 1 through 5
measure: Return to Fertility. Only for subjects requesting LevoCept 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.
measure: Release rate of LNG from the IUS and resulting pharmacokinetics of LNG (PK substudy)
timeFrame: Years 1 through 5
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Essential Access Health-Berkeley
state: California
city: Los Angeles
country: United States
facility: Essential Access Health-Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California Davis Health System Department of Obstetrics and Gynecology
state: California
city: San Diego
country: United States
facility: WR-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: Aurora
country: United States
facility: University Of Colorado Department of Obstetrics & Gyncology
state: Colorado
city: Atlanta
country: United States
facility: Emory University School of Medicine Gynecology/Obstetrics
state: Georgia
city: Decatur
country: United States
facility: Soapstone Center for Clinical Research
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Indianapolis
country: United States
facility: IU Health University Hospital
state: Indiana
city: Minneapolis
country: United States
facility: Planned Parenthood North Central States
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: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati/Reproductive Medicine Research
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Ob/Gyn Research Office
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Clinical Research of Philadelphia, LLC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital, Center for Family Planning Research
state: Pennsylvania
city: Houston
country: United States
facility: Advances In Health
state: Texas
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, Research, Gynecology
state: Washington
Study officials:
References: