Clinical trial NCT03021915: Single Center, Prospective Controlled Pilot Study of the OvaPrime Procedure
Official title: Single Center, Prospective Controlled Pilot Study of the OvaPrime Procedure
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Primary Ovarian Insufficiency
Poor Ovarian Response
Lead sponsor: OvaScience, Inc.
Sponsor class: INDUSTRY
First posted: 2017-01-16
Enrollment: 81
Sex: ALL
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single center, prospective, controlled pilot safety research study. The primary objective of this research study is to assess the safety with the use of the OvaPrime procedure in women who are diagnosed with either primary ovarian insufficiency (POI) or poor ovarian response (POR).

A maximum of ninety-five (95) subjects will be enrolled consisting of a minimum of thirty (30) POI subjects and a minimum of fifty (50) POR to achieve the target sample size of 70 Modified Intent-to-Treat (mITT) subjects as the primary analysis population. Each subject shall have one ovary exposed to the EggPC cells while the contralateral ovary is exposed to the EggPC vehicle as a means to have each subject serve as their own control. Results between the treatment and control ovary will be examined for relevant endpoints such as antral follicle counts.

The duration of the research study is estimated at approximately 6 years total, for the period spanning enrollment (estimated at approximately six months), eight months to the last hyperstimulation and through completion of 5-year follow-up (main study protocol with one year primary endpoint and LTFU sub-study which extends to 5 additional years).


Eligibility criteria: Inclusion Criteria:

1. Subjects who are diagnosed with EITHER POI or POR as defined below:

   * POI subjects who are:

     * \< 40 years of age
     * have non-detectable AMH
     * FSH \>15.0 mIU/ml and/or symptoms of menopause
   * POR (based on European Society of Human Reproduction and Embryology (ESHRE) guidelines must have two of the following:

     * 40 years of age

       * A previous IVF cycle with \< 3 oocytes with a standard of care controlled ovarian hyperstimulation protocol
       * An abnormal ovarian reserve test defined as:

         1. AFC \< 5 - 7 follicles or
         2. AMH \< 0.5 - 1.1 ng/ml or
         3. Highest ever baseline FSH \> 15.0 ml U/ml
2. Subject must have both ovaries.
3. Subject agrees to participate in main study follow up as well as Long Term Follow-up (LTFU) sub-study
4. Subject's male partner or sperm donor source must meet the following requirements:

   * Semen must be an ejaculate (not surgically derived, epididymal, testicular, electro- ejaculated sperm), collected by ejaculation.
   * Male partner's testes must not have been exposed to chemotherapy.
   * Semen must have some morphologically normal spermatozoa according to the World Health Organization (see table below) and adequate concentration with some motile spermatozoa for insemination of all oocytes by intra-cytoplasmic sperm injection (ICSI).

   WHO Semen variable 2010 Volume (mL) 1.5 Concentration (106 mL-1) 15 Total sperm number (106/ejaculate) 39 Motility (% motile) 40 (a + b + c) Forward progression 32 (a + b) Morphology (% normal) 4 Viability/vitality (% live) 58 White blood cells (106 mL-1) \< 1.0
5. Partner must also agree to all research study requirements including follow up (including main study as well as LTFU sub-study) of offspring and sign consent form (not applicable in the case of a woman using sperm donation).

Exclusion Criteria:

1. Subject with a diagnosis of POI who is ≥ 40 years of age or \< 21 years of age at the time of the OvaPrime procedure
2. Subject with onset of POI \< 18 years of age
3. Subject with a diagnosis of POR who is \> 45 years of age at the time of the OvaPrime procedure
4. Subject has had any prior surgery/medical condition that would prevent direct access to the ovaries (e.g., pelvic adhesions, tubo- ovarian adhesions location/displacement of the ovary(ies) or high body mass index (BMI)).
5. Subject has severe (stage IV) endometriosis or presence of an endometrioma
6. Subject has a unilateral or bilateral untreated hydrosalpinx
7. Subject has participated in the active phase of another investigational trial within the previous 30 days
8. Subject has a history of prior chemotherapy or radiation therapy to the pelvis
9. Subjects and/or partner (supplying sperm) with known karyotypic abnormalities 10. Subjects with POI who have FMR1 premutations or an FMRI mutation

11. Subjects who are positive for the hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) and human immunodeficiency virus (HIV).

Primary outcomes:
measure: Safety - to evaluate the frequency of adverse events (AE) and serious adverse events (SAE) of all subjects regardless of pregnancy.
timeFrame: 2 years
Secondary outcomes:
measure: Hormone level change from baseline in the following: anti-mullerian hormone level (AMH), follicle stimulating hormone (FSH) and estradiol (E2)
timeFrame: 1 year
measure: Development of new primordial or growing follicles in the treated ovary as determined by decreasing serum FSH
timeFrame: 1 year
measure: Development of new primordial or growing follicles in the treated ovary as determined by increasing serum AMH
timeFrame: 1 year
measure: Development of new primordial or growing follicles in the treated ovary as determined by the presence of new basal antral follicles on ultrasound
timeFrame: 1 year
measure: Development of new primordial or growing follicles in the treated ovary as determined by increasing serum E2
timeFrame: 1 year
measure: Egg maturation and developmental potential as evidenced by: Number of MII eggs as assessed by embryologist.
timeFrame: 1 year
measure: Egg maturation and developmental potential as evidenced by: Number of embryos on Day 5 that are graded 3BB or greater as assessed by embryologist
timeFrame: 1 year
measure: Egg maturation and developmental potential as evidenced by: Number of embryo transfers
timeFrame: 1 year
measure: Pre-implantation Genetic Screening (PGS) results
timeFrame: 1 year
measure: The occurrence of pregnancy
timeFrame: 2 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: TRIO
state: Ontario
Study officials:
affiliation: TRIO Fertility Clinic
name: Dan Nayot, MD
role: PRINCIPAL_INVESTIGATOR
References: