Women at Risk for Pregnancy
Conditions
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.
Interventions
DRUGVeraCept
VeraCept Intrauterine Contraceptive is a hormone free, low dose, copper-releasing birth control method
Sponsors
Syneos Health
Sebela Women's Health Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
VeraCept Intrauterine System (IUS)
Eligibility
Sex/Gender
FEMALE
Age
No minimum to 45 Years
Healthy volunteers
Yes
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 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 21-24 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 with ASC-US results, must also have a 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 IUS insertion. Alternatively, the subject must have had a colposcopy performed within the appropriate screen timeframe, and prior to the study IUS 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 system (IUS) that has not been removed by the time the study IUS is placed; 4. History of previous IUS complications, such as perforation, expulsion, or pregnancy with IUS in place; 5. Pain with current IUS; 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 IUS; 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 or unresolved acute cervicitis or vaginitis; 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 or LevoCept study; 21a. Subject has been enrolled in a previous VeraCept or LevoCept study where VeraCept or LevoCept placement was successful or attempted (replaces exclusion #21 for PK sub-study subjects only); 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. 25. Subject is \<4 weeks post-pregnancy (postpartum, spontaneous or induced abortion)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Contraceptive Efficacy Through 3 Years of Use | 3 years | Contraceptive efficacy through 3 years of use, as assessed by the Pearl Index. The Pearl Index is calculated as the number of on-treatment pregnancies per 100 woman-years of exposure. On-treatment pregnancy is defined as the estimated conception date being on or after the insertion date (must be a successful insertion) and no more than 7 days after the study drug is removed or expelled. One women year is defined as comprising thirteen 28-day cycles. A lower Pearl Index indicates greater contraceptive effectiveness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding and Spotting Patterns | Through year 1 | Bleeding and spotting patterns will be summarized 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 |
| Insertion Pain Assessed Immediately After Insertion (First Attempt) | Visit 1 (Day 1), immediately after insertion | Insertion pain summarized for subjects at first attempt as reported by the subjects |
| Cumulative VeraCept Discontinuation Rates | Years 1 through 3 | Cumulative VeraCept discontinuation rates will be summarized using Kaplan-Meier methods for the Safety population. |
| Contraceptive Efficacy at Years 4, 5, 6, 7 and 8 | Years 4, 5, 6, 7, and 8 and cumulatively through 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 |
| VeraCept Placement Success | Visit 1 (Day 1) / VeraCept placement | The number and percentage of subjects with either a successful or unsuccessful placement will be summarized for the ITT |
| Ease of VeraCept Placement | Visit 1 (Day 1) / VeraCept placement | Ease of VeraCept placement will be summarized for the ITT population as reported by the investigator (Very easy, Easy, Neither Easy nor Hard, Hard, Very Hard). (First Attempt) |
| Cumulative VeraCept Expulsion Rates | Years 1 through 3 | Cumulative VeraCept expulsion rates will be summarized using Kaplan-Meier methods for the Safety population. |
| Return to Fertility. Only for Subjects Requesting VeraCept Removal to Become Pregnant. | Subjects will be followed for either 1 year, until they decide to no longer try to conceive or they become pregnant, whichever comes first. | The number and percentage of subjects with each return to fertility response will be summarized for the Safety population. |
| Safety Adverse Events of Special Interest: Pelvic Infection (PID or Endometriosis), Uterine Perforations, and Abdominal Pain | 3 years | — |
| Cumulative Pregnancy Percentage | Years 1 through 3 | A life table analysis (using Kaplan-Meier) of pregnancies will be performed for the EP population to present the cumulative pregnancy percentage |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VeraCept VeraCept® Intrauterine Contraceptive
VeraCept: VeraCept Intrauterine Contraceptive is a hormone free, low dose, copper-releasing birth control method | 1,620 |
| Total | 1,620 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 349 |
| Overall Study | Lost to Follow-up | 97 |
| Overall Study | ongoing within third year of study | 106 |
| Overall Study | other | 39 |
| Overall Study | Physician Decision | 9 |
| Overall Study | Pregnancy | 20 |
| Overall Study | Protocol Violation | 4 |
| Overall Study | unsuccessful study drug placement | 19 |
| Overall Study | Withdrawal by Subject | 288 |
Baseline characteristics
| Characteristic | VeraCept |
|---|---|
| Age, Continuous | 27.6 years STANDARD_DEVIATION 5.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 308 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1312 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 18 Participants |
| Race (NIH/OMB) Asian | 86 Participants |
| Race (NIH/OMB) Black or African American | 238 Participants |
| Race (NIH/OMB) More than one race | 62 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 10 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants |
| Race (NIH/OMB) White | 1196 Participants |
| Sex: Female, Male Female | 1620 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 1,620 |
| other Total, other adverse events | 1,551 / 1,601 |
| serious Total, serious adverse events | 52 / 1,620 |
Outcome results
Primary
Contraceptive Efficacy Through 3 Years of Use
Contraceptive efficacy through 3 years of use, as assessed by the Pearl Index. The Pearl Index is calculated as the number of on-treatment pregnancies per 100 woman-years of exposure. On-treatment pregnancy is defined as the estimated conception date being on or after the insertion date (must be a successful insertion) and no more than 7 days after the study drug is removed or expelled. One women year is defined as comprising thirteen 28-day cycles. A lower Pearl Index indicates greater contraceptive effectiveness.
Time frame: 3 years
Population: Evaluable for pregnancy population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VeraCept | Contraceptive Efficacy Through 3 Years of Use | 1.06 Pearl Index |
Secondary
Bleeding and Spotting Patterns
Bleeding and spotting patterns will be summarized 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
Time frame: Through year 1
Population: evaluable for cycle control population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VeraCept | Bleeding and Spotting Patterns | cycle 10: bleeding or spotting | 6.9 days | Standard Deviation 3.4 |
| VeraCept | Bleeding and Spotting Patterns | cycle 1: bleeding or spotting | 11.2 days | Standard Deviation 4.93 |
| VeraCept | Bleeding and Spotting Patterns | cycle 1: bleeding only | 6.4 days | Standard Deviation 3.44 |
| VeraCept | Bleeding and Spotting Patterns | cycle 1: spotting only | 4.8 days | Standard Deviation 3.37 |
| VeraCept | Bleeding and Spotting Patterns | cycle 2: bleeding or spotting | 7.8 days | Standard Deviation 3.76 |
| VeraCept | Bleeding and Spotting Patterns | cycle 2: bleeding only | 5.1 days | Standard Deviation 2.57 |
| VeraCept | Bleeding and Spotting Patterns | cycle 2: spotting only | 2.7 days | Standard Deviation 2.56 |
| VeraCept | Bleeding and Spotting Patterns | cycle 3: bleeding or spotting | 7.6 days | Standard Deviation 3.73 |
| VeraCept | Bleeding and Spotting Patterns | cycle 3: bleeding only | 5.0 days | Standard Deviation 2.69 |
| VeraCept | Bleeding and Spotting Patterns | cycle 3: spotting only | 2.5 days | Standard Deviation 2.43 |
| VeraCept | Bleeding and Spotting Patterns | cycle 4: bleeding or spotting | 7.3 days | Standard Deviation 3.77 |
| VeraCept | Bleeding and Spotting Patterns | cycle 4: bleeding only | 4.9 days | Standard Deviation 2.66 |
| VeraCept | Bleeding and Spotting Patterns | cycle 4: spotting only | 2.4 days | Standard Deviation 2.54 |
| VeraCept | Bleeding and Spotting Patterns | cycle 5: bleeding or spotting | 7.2 days | Standard Deviation 3.63 |
| VeraCept | Bleeding and Spotting Patterns | cycle 5: bleeding only | 4.8 days | Standard Deviation 2.6 |
| VeraCept | Bleeding and Spotting Patterns | cycle 5: spotting only | 2.4 days | Standard Deviation 2.33 |
| VeraCept | Bleeding and Spotting Patterns | cycle 6: bleeding or spotting | 7.0 days | Standard Deviation 3.48 |
| VeraCept | Bleeding and Spotting Patterns | cycle 6: bleeding only | 4.8 days | Standard Deviation 2.64 |
| VeraCept | Bleeding and Spotting Patterns | cycle 6: spotting only | 2.2 days | Standard Deviation 2.27 |
| VeraCept | Bleeding and Spotting Patterns | cycle 7: bleeding or spotting | 7.2 days | Standard Deviation 3.79 |
| VeraCept | Bleeding and Spotting Patterns | cycle 7: bleeding only | 4.7 days | Standard Deviation 2.73 |
| VeraCept | Bleeding and Spotting Patterns | cycle 7: spotting only | 2.4 days | Standard Deviation 2.52 |
| VeraCept | Bleeding and Spotting Patterns | cycle 8: bleeding or spotting | 7.0 days | Standard Deviation 3.54 |
| VeraCept | Bleeding and Spotting Patterns | cycle 8: bleeding only | 4.7 days | Standard Deviation 2.43 |
| VeraCept | Bleeding and Spotting Patterns | cycle 8: spotting only | 2.3 days | Standard Deviation 2.51 |
| VeraCept | Bleeding and Spotting Patterns | cycle 9: bleeding or spotting | 6.9 days | Standard Deviation 3.6 |
| VeraCept | Bleeding and Spotting Patterns | cycle 9: bleeding only | 4.6 days | Standard Deviation 2.58 |
| VeraCept | Bleeding and Spotting Patterns | cycle 9: spotting only | 2.2 days | Standard Deviation 2.36 |
| VeraCept | Bleeding and Spotting Patterns | cycle 10: bleeding only | 4.6 days | Standard Deviation 2.44 |
| VeraCept | Bleeding and Spotting Patterns | cycle 10: spotting only | 2.3 days | Standard Deviation 2.19 |
| VeraCept | Bleeding and Spotting Patterns | cycle 11: bleeding or spotting | 6.8 days | Standard Deviation 3.48 |
| VeraCept | Bleeding and Spotting Patterns | cycle 11: bleeding only | 4.5 days | Standard Deviation 2.38 |
| VeraCept | Bleeding and Spotting Patterns | cycle 11: spotting only | 2.2 days | Standard Deviation 2.6 |
| VeraCept | Bleeding and Spotting Patterns | cycle 12: bleeding or spotting | 6.8 days | Standard Deviation 3.38 |
| VeraCept | Bleeding and Spotting Patterns | cycle 12: bleeding only | 4.7 days | Standard Deviation 2.55 |
| VeraCept | Bleeding and Spotting Patterns | cycle 12: spotting only | 2.2 days | Standard Deviation 2.24 |
| VeraCept | Bleeding and Spotting Patterns | cycle 13: bleeding or spotting | 6.9 days | Standard Deviation 3.5 |
| VeraCept | Bleeding and Spotting Patterns | cycle 13: bleeding only | 4.6 days | Standard Deviation 2.5 |
| VeraCept | Bleeding and Spotting Patterns | cycle 13: spotting only | 2.2 days | Standard Deviation 2.4 |
Secondary
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
Time frame: Years 4, 5, 6, 7, and 8 and cumulatively through Years 4, 5, 6, 7, and 8
Secondary
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
Time frame: Years 1 through 3
Population: evaluable for pregnancy population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VeraCept | Cumulative Pregnancy Percentage | Year 1 | 0.013 Probability |
| VeraCept | Cumulative Pregnancy Percentage | Year 2 | 0.024 Probability |
| VeraCept | Cumulative Pregnancy Percentage | Year 3 | 0.028 Probability |
Secondary
Cumulative VeraCept Discontinuation Rates
Cumulative VeraCept discontinuation rates will be summarized using Kaplan-Meier methods for the Safety population.
Time frame: Years 1 through 3
Population: safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VeraCept | Cumulative VeraCept Discontinuation Rates | Year 1 | 0.195 Probability |
| VeraCept | Cumulative VeraCept Discontinuation Rates | Year 2 | 0.329 Probability |
| VeraCept | Cumulative VeraCept Discontinuation Rates | Year 3 | 0.419 Probability |
Secondary
Cumulative VeraCept Expulsion Rates
Cumulative VeraCept expulsion rates will be summarized using Kaplan-Meier methods for the Safety population.
Time frame: Years 1 through 3
Population: safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VeraCept | Cumulative VeraCept Expulsion Rates | Year 1 | 0.025 Probability |
| VeraCept | Cumulative VeraCept Expulsion Rates | Year 2 | 0.040 Probability |
| VeraCept | Cumulative VeraCept Expulsion Rates | Year 3 | 0.051 Probability |
Secondary
Ease of VeraCept Placement
Ease of VeraCept placement will be summarized for the ITT population as reported by the investigator (Very easy, Easy, Neither Easy nor Hard, Hard, Very Hard). (First Attempt)
Time frame: Visit 1 (Day 1) / VeraCept placement
Population: Number of subjects in ITT population with available information regarding ease of placement at first attempt.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VeraCept | Ease of VeraCept Placement | very easy | 844 Participants |
| VeraCept | Ease of VeraCept Placement | easy | 502 Participants |
| VeraCept | Ease of VeraCept Placement | neither easy nor hard | 160 Participants |
| VeraCept | Ease of VeraCept Placement | hard | 77 Participants |
| VeraCept | Ease of VeraCept Placement | very hard | 26 Participants |
Secondary
Insertion Pain Assessed Immediately After Insertion (First Attempt)
Insertion pain summarized for subjects at first attempt as reported by the subjects
Time frame: Visit 1 (Day 1), immediately after insertion
Population: Number of subjects in ITT population with available information regarding device placement pain at first attempt.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VeraCept | Insertion Pain Assessed Immediately After Insertion (First Attempt) | no pain | 85 Participants |
| VeraCept | Insertion Pain Assessed Immediately After Insertion (First Attempt) | some pain | 363 Participants |
| VeraCept | Insertion Pain Assessed Immediately After Insertion (First Attempt) | moderately painful | 661 Participants |
| VeraCept | Insertion Pain Assessed Immediately After Insertion (First Attempt) | painful | 406 Participants |
| VeraCept | Insertion Pain Assessed Immediately After Insertion (First Attempt) | very painful | 85 Participants |
Secondary
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.
Time frame: Subjects will be followed for either 1 year, until they decide to no longer try to conceive or they become pregnant, whichever comes first.
Population: Number of subjects requesting VeraCept removal to become pregnant with known fertility outcomes
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VeraCept | Return to Fertility. Only for Subjects Requesting VeraCept Removal to Become Pregnant. | pregnancy occurred | 37 Participants |
| VeraCept | Return to Fertility. Only for Subjects Requesting VeraCept Removal to Become Pregnant. | pregnancy did not occur | 14 Participants |
Secondary
Safety Adverse Events of Special Interest: Pelvic Infection (PID or Endometriosis), Uterine Perforations, and Abdominal Pain
Time frame: 3 years
Population: safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VeraCept | Safety Adverse Events of Special Interest: Pelvic Infection (PID or Endometriosis), Uterine Perforations, and Abdominal Pain | uterine perforation | 2 participants |
| VeraCept | Safety Adverse Events of Special Interest: Pelvic Infection (PID or Endometriosis), Uterine Perforations, and Abdominal Pain | pelvic infection (PID or endometriosis) | 19 participants |
| VeraCept | Safety Adverse Events of Special Interest: Pelvic Infection (PID or Endometriosis), Uterine Perforations, and Abdominal Pain | abdominal pain | 111 participants |
Secondary
VeraCept Placement Success
The number and percentage of subjects with either a successful or unsuccessful placement will be summarized for the ITT
Time frame: Visit 1 (Day 1) / VeraCept placement
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VeraCept | VeraCept Placement Success | successful first attempt of placement | 1549 Participants |
| VeraCept | VeraCept Placement Success | successful second attempt of placement | 52 Participants |
| VeraCept | VeraCept Placement Success | failed placement | 7 Participants |
| VeraCept | VeraCept Placement Success | second attempt not tried | 12 Participants |