Casea S Contraceptive Implants (Casea S) Trial

Phase 1

Active, not recruiting

• Conditions: Contraception
• Interventions: Drug: 22.2 mg Etonogestrel (ENG); Drug: 44.4 mg Etonogestrel (ENG)

• Registration Number: NCT05174884
• Lead Sponsor: FHI 360

Brief Summary

This is a single-center, two-part, Phase 1 study to evaluate the pharmacokinetics (PK) of ENG, removability, safety, and tolerability of Casea S pellets inserted subdermally in healthy women of reproductive age. The goal is to select for further investigation a dose of Casea S that is both safe and has a PK profile consistent with contraceptive protection for at least 78 weeks.

Detailed Description

In Part 1 of this study, four women will each have a single Casea S pellet (22.2 mg ENG) inserted into the inner aspect of the non-dominant upper arm after a negative urine pregnancy test. The insertion site and pellet location will be verified, marked, and photographed. ISRs and AEs will be assessed.

In Part 2 of this study, approximately sixteen women will each have two Casea S pellets (44.4 mg ENG) inserted into the inner aspect of the non-dominant upper arm. The insertion site and pellet location will be verified, marked, and photographed. ISRs and AEs will be assessed.

Study Timeline

• Study First Submitted: 2021-08-25
• Study First Submitted QC: 2021-12-14
• Study First Posted: 2022-01-03
• Study Start: 2023-12-13
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-10
• Last Update Posted: 2025-04-13
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

Participants may be included in the study if they meet all of the following criteria:

• willing and able to provide signed informed consent
• female between 18 to 45 years of age (inclusive)
• healthy based on results of medical evaluation including medical history, vital signs, and physical exam
• has regular menstrual cycle (21 to 35 days)
• not at risk for pregnancy (i.e., sterilized)
• has a Body Mass Index (BMI) of 18 to 29.9
• provides normal mammogram results within the last year before enrollment for women 40 or older
• is willing and able to comply with all study requirements and return to the investigational site for the follow-up procedures and assessments as specified in this protocol
• Part 2 participants only: has daily access to a smartphone, tablet, or computer with internet access.

Exclusion Criteria

Participants will be excluded from participating in this study if they meet any of the following criteria:

• has multiple risk factors for cardiovascular disease (e.g., smoking, diabetes, obesity, hypertension, high LDL (low density lipoprotein), or high triglyceride levels)

• has current or history of ischemic heart disease or cerebrovascular disease

• has current or previous thromboembolic disorders

• has systemic lupus erythematosus

• has rheumatoid arthritis on immunosuppressive therapy

• has migraine with aura

• has undiagnosed abnormal vaginal bleeding

• has known or suspected breast cancer, history of breast cancer or other progestin-sensitive cancer

• has current or history of cervical cancer

• has cirrhosis, liver tumors (benign or malignant), or active liver disease

• has one or more baseline liver function test(s) above the local laboratory's normal range

• has a hemoglobin <10.5 g/dL

• has used any injectable contraceptive in the past 6 months

• has used any of the following medications within 4 weeks before enrollment:

  • any investigational drug
  • prohibited drugs (listed in Section 6.3.3.4.4.1 of the study protocol)
  • oral contraceptives, contraceptive ring, or patch
  • levonorgestrel intrauterine device (LNG IUD) or contraceptive implant

• is pregnant

• is currently breastfeeding

• desires to become pregnant in the subsequent 30 months

• has been pregnant in last 3 months

• is using or planning to use prohibited drugs for their intended study duration

• has abnormal cervical cytology requiring treatment

• has known sensitivity to ENG

• plans to move to another location in the next 30 months

• is participating in any other clinical trial with a biomedical intervention

• has any condition (social or medical), that in the opinion of the site investigator would make study participation unsafe, would interfere with adherence to the clinical study requirements, or complicate data interpretation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Single Casea S pellet	22.2 mg Etonogestrel (ENG)	In Part 1 of this study, four women will each have a single Casea S pellet (22.2 mg ENG) inserted into the inner aspect of the non-dominant upper arm.
Two Casea S pellets	44.4 mg Etonogestrel (ENG)	In Part 2 of this study, sixteen women will each have two Casea S pellets (44.4 mg ENG) inserted into the inner aspect of the non-dominant upper arm.

Primary Outcome Measures

Name	Time	Method
Maximum observed serum concentration (Cmax)	12 weeks; 52 weeks; 114 weeks	Maximum observed serum concentration (Cmax) measured by blood samples collected at multiple timepoints before and after pellet insertion
Time to Cmax (tmax)	12 weeks; 52 weeks; 114 weeks	Time to Cmax (tmax) measured by blood samples collected at multiple timepoints before and after pellet insertion
Geometric mean serum ENG concentration	28 days; 114 weeks	Geometric mean serum ENG concentration at treatment days 28 and 84
Area under concentration time curve (AUC 0-28)	28 days; 154 days; 364 days	Area under the concentration time curve through days 28 and day 84
Predicted concentration at day 546 and probability of exceeding 90 pg/mL through day 546	52 weeks	pharmacokinetics of ENG after subdermal insertion of 2 Casea S pellets
Assessment of the removability of Casea S pellets	up to 52 weeks	Number and descriptions of incidence of removal complications
Assessment Casea S pellets removability	up to 52 weeks	Time of the procedure duration of procedure
Ability to completely remove the pellet and ease of removal	up to 52 weeks	Physician's assessment of the removability of Casea S pellets qualified as "complete removal, partial removal, or not removed" on the study removal assessment.
Time to undetectable ENG levels	114 weeks	Apparent absorption half-life; Predicted concentration at day 546 and probability of exceeding 90 pg/mL through day 546; Time above 90 pg/mL

Secondary Outcome Measures

Name	Time	Method
Occurrence of treatment emergency adverse events, significant changes in vital signs, weight, vaginal bleeding patterns and perceptions, abnormalities in serum chemistry, occurrence of implant site reactions	up to 114 weeks	Safety and tolerability of Casea S pellets measured by the occurrence of treatment emergency adverse events, significant changes in vital signs, weight, vaginal bleeding patterns and perceptions, abnormalities in serum chemistry, occurrence of implant site reactions
Assessment of the complications of insertion of Casea S pellets	up to 114 weeks	Number and descriptions of the incidence of insertion complications.
Assessment of the ease of insertion of Casea S pellets	up to 114 weeks	Physician's report of success and ease of insertion. Ease of insertion qualified as "easy, moderate, or difficult" on the study insertion assessment.
Assessment of the duration of Casea S pellets insertion	up to 114 weeks	Time of the procedure duration
Follicular and luteal activity following subdermal insertion of Casea S pellets	up to 114 weeks	Estradiol (E2) and progesterone (P4) levels
Estimate of ENG release rates using explant analysis	up to 114 weeks	Cumulative amount of ENG released over time, average daily release in 3 months and up to 130 weeks

Trial Locations

Locations (1)

Clinica Profamilia; 🇩🇴 Santo Domingo, DN, Dominican Republic