Back to resultsSingle Center, Prospective Controlled Pilot Study of the OvaPrime Procedure
Primary Purpose
Primary Ovarian Insufficiency, Poor Ovarian Response
Status
Suspended
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
OvaPrime Treatment
Sponsored by
About this trial
This is an interventional treatment trial for Primary Ovarian Insufficiency
Eligibility Criteria
Inclusion Criteria:
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:
- AFC < 5 - 7 follicles or
- AMH < 0.5 - 1.1 ng/ml or
- Highest ever baseline FSH > 15.0 ml U/ml
- Subject must have both ovaries.
- Subject agrees to participate in main study follow up as well as Long Term Follow-up (LTFU) sub-study
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
- 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:
- Subject with a diagnosis of POI who is ≥ 40 years of age or < 21 years of age at the time of the OvaPrime procedure
- Subject with onset of POI < 18 years of age
- Subject with a diagnosis of POR who is > 45 years of age at the time of the OvaPrime procedure
- 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)).
- Subject has severe (stage IV) endometriosis or presence of an endometrioma
- Subject has a unilateral or bilateral untreated hydrosalpinx
- Subject has participated in the active phase of another investigational trial within the previous 30 days
- Subject has a history of prior chemotherapy or radiation therapy to the pelvis
- 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).
Sites / Locations
- TRIO
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
OvaPrime Treatment
Arm Description
The treatment is based on identified EggPC cells in the outer-most layer of the ovary. During OvaPrime, the EggPC cells are isolated from biopsy tissue obtained from the outer layer of the ovary. OvaScience separates the EggPC cells and these isolated cells are then returned to the IVF clinic - there is no culture or expansion of the EggPC cells during this process. Upon receipt of the autologous EggPC cells, the clinic initiates the process of reintroducing the cells into the follicular development zone of the woman's own ovary using a laparoscopic procedure. Once in the ovary, the EggPC cells have the opportunity to develop and mature into fertilizable eggs naturally or with controlled ovarian hyperstimulation (when stimulated by exogenous gonadotropins) using standard IVF protocols.
Outcomes
Primary Outcome Measures
Safety - to evaluate the frequency of adverse events (AE) and serious adverse events (SAE) of all subjects regardless of pregnancy.
For subjects who fail to achieve pregnancy, they will be assessed for one year from the date of the OvaPrime procedure. For subjects who become pregnant, they will be followed through the pregnancy and 1-year post-partum. The safety of the off-spring will be monitored by this research study up to one-year post delivery in the main study and for up to 5 years in the long-term follow-up study.
Secondary Outcome Measures
Hormone level change from baseline in the following: anti-mullerian hormone level (AMH), follicle stimulating hormone (FSH) and estradiol (E2)
Development of new primordial or growing follicles in the treated ovary as determined by decreasing serum FSH
Development of new primordial or growing follicles in the treated ovary as determined by increasing serum AMH
Development of new primordial or growing follicles in the treated ovary as determined by the presence of new basal antral follicles on ultrasound
Development of new primordial or growing follicles in the treated ovary as determined by increasing serum E2
Egg maturation and developmental potential as evidenced by: Number of MII eggs as assessed by embryologist.
Egg maturation and developmental potential as evidenced by: Number of embryos on Day 5 that are graded 3BB or greater as assessed by embryologist
Egg maturation and developmental potential as evidenced by: Number of embryo transfers
Pre-implantation Genetic Screening (PGS) results
The occurrence of pregnancy
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03021915
Brief Title
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
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Suspended
Why Stopped
OvaScience, Inc. is no longer study sponsor as it is undergoing a merger. Follow-up will be conducted by sponsor-investigator Dr. Bob Casper.
Study Start Date
October 2016 (undefined)
Primary Completion Date
June 2022 (Anticipated)
Study Completion Date
June 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
OvaScience, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Ovarian Insufficiency, Poor Ovarian Response
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
81 (Actual)
8. Arms, Groups, and Interventions
Arm Title
OvaPrime Treatment
Arm Type
Other
Arm Description
The treatment is based on identified EggPC cells in the outer-most layer of the ovary. During OvaPrime, the EggPC cells are isolated from biopsy tissue obtained from the outer layer of the ovary. OvaScience separates the EggPC cells and these isolated cells are then returned to the IVF clinic - there is no culture or expansion of the EggPC cells during this process. Upon receipt of the autologous EggPC cells, the clinic initiates the process of reintroducing the cells into the follicular development zone of the woman's own ovary using a laparoscopic procedure. Once in the ovary, the EggPC cells have the opportunity to develop and mature into fertilizable eggs naturally or with controlled ovarian hyperstimulation (when stimulated by exogenous gonadotropins) using standard IVF protocols.
Intervention Type
Other
Intervention Name(s)
OvaPrime Treatment
Intervention Description
The treatment is based on identified EggPC cells in the outer-most layer of the ovary. During OvaPrime, the EggPC cells are isolated from biopsy tissue obtained from the outer layer of the ovary. OvaScience separates the EggPC cells and these isolated cells are then returned to the IVF clinic - there is no culture or expansion of the EggPC cells during this process. Upon receipt of the autologous EggPC cells, the clinic initiates the process of reintroducing the cells into the follicular development zone of the woman's own ovary using a laparoscopic procedure. Once in the ovary, the EggPC cells have the opportunity to develop and mature into fertilizable eggs naturally or with controlled ovarian hyperstimulation (when stimulated by exogenous gonadotropins) using standard IVF protocols.
Primary Outcome Measure Information:
Title
Safety - to evaluate the frequency of adverse events (AE) and serious adverse events (SAE) of all subjects regardless of pregnancy.
Description
For subjects who fail to achieve pregnancy, they will be assessed for one year from the date of the OvaPrime procedure. For subjects who become pregnant, they will be followed through the pregnancy and 1-year post-partum. The safety of the off-spring will be monitored by this research study up to one-year post delivery in the main study and for up to 5 years in the long-term follow-up study.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Hormone level change from baseline in the following: anti-mullerian hormone level (AMH), follicle stimulating hormone (FSH) and estradiol (E2)
Time Frame
1 year
Title
Development of new primordial or growing follicles in the treated ovary as determined by decreasing serum FSH
Time Frame
1 year
Title
Development of new primordial or growing follicles in the treated ovary as determined by increasing serum AMH
Time Frame
1 year
Title
Development of new primordial or growing follicles in the treated ovary as determined by the presence of new basal antral follicles on ultrasound
Time Frame
1 year
Title
Development of new primordial or growing follicles in the treated ovary as determined by increasing serum E2
Time Frame
1 year
Title
Egg maturation and developmental potential as evidenced by: Number of MII eggs as assessed by embryologist.
Time Frame
1 year
Title
Egg maturation and developmental potential as evidenced by: Number of embryos on Day 5 that are graded 3BB or greater as assessed by embryologist
Time Frame
1 year
Title
Egg maturation and developmental potential as evidenced by: Number of embryo transfers
Time Frame
1 year
Title
Pre-implantation Genetic Screening (PGS) results
Time Frame
1 year
Title
The occurrence of pregnancy
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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:
AFC < 5 - 7 follicles or
AMH < 0.5 - 1.1 ng/ml or
Highest ever baseline FSH > 15.0 ml U/ml
Subject must have both ovaries.
Subject agrees to participate in main study follow up as well as Long Term Follow-up (LTFU) sub-study
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
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:
Subject with a diagnosis of POI who is ≥ 40 years of age or < 21 years of age at the time of the OvaPrime procedure
Subject with onset of POI < 18 years of age
Subject with a diagnosis of POR who is > 45 years of age at the time of the OvaPrime procedure
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)).
Subject has severe (stage IV) endometriosis or presence of an endometrioma
Subject has a unilateral or bilateral untreated hydrosalpinx
Subject has participated in the active phase of another investigational trial within the previous 30 days
Subject has a history of prior chemotherapy or radiation therapy to the pelvis
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dan Nayot, MD
Organizational Affiliation
TRIO Fertility Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
TRIO
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2K4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Single Center, Prospective Controlled Pilot Study of the OvaPrime Procedure
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