Clinical trial NCT05174884: Casea S Contraceptive Implants (Casea S) Trial
Official title: A Phase 1 Clinical Trial to Evaluate the Pharmacokinetics, Removability, Safety, and Tolerability of Casea S Contraceptive Implants
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Contraception
Keywords: Long Acting Reversible Contraceptive
Lead sponsor: FHI 360
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2022-01-03
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum observed serum concentration (Cmax)
timeFrame: 12 weeks; 52 weeks; 114 weeks
measure: Time to Cmax (tmax)
timeFrame: 12 weeks; 52 weeks; 114 weeks
measure: Geometric mean serum ENG concentration
timeFrame: 28 days; 114 weeks
measure: Area under concentration time curve (AUC 0-28)
timeFrame: 28 days; 154 days; 364 days
measure: Predicted concentration at day 546 and probability of exceeding 90 pg/mL through day 546
timeFrame: 52 weeks
measure: Assessment of the removability of Casea S pellets
timeFrame: up to 52 weeks
measure: Assessment Casea S pellets removability
timeFrame: up to 52 weeks
measure: Ability to completely remove the pellet and ease of removal
timeFrame: up to 52 weeks
measure: Time to undetectable ENG levels
timeFrame: 114 weeks
Secondary outcomes:
measure: 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
timeFrame: up to 114 weeks
measure: Assessment of the ease of insertion of Casea S pellets
timeFrame: up to 114 weeks
measure: Assessment of the duration of Casea S pellets insertion
timeFrame: up to 114 weeks
measure: Assessment of the complications of insertion of Casea S pellets
timeFrame: up to 114 weeks
measure: Follicular and luteal activity following subdermal insertion of Casea S pellets
timeFrame: up to 114 weeks
measure: Estimate of ENG release rates using explant analysis
timeFrame: up to 114 weeks
Other outcomes:
Locations:
city: Santo Domingo
country: Dominican Republic
facility: Clinica Profamilia
state: DN
Study officials:
affiliation: FHI 360
name: Kavita Nanda, M.D.
role: PRINCIPAL_INVESTIGATOR
References: