Asherman's syndrome also known as intrauterine synechiae MedDRA version: 21.1 Level: PT Classification code 10053868 Term: Asherman's syndrome System Organ Class: 10038604 - Reproductive system and breast disorders
Conditions
Interventions
Product Name: Not available
Product Code: IGX1
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Autologous adult bone marrow-derived and unexpanded CD 133+ hematopoietic stem cells c
Sponsors
Asherman Therapy S.L.U.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients whose written informed consent approved by the Ethics Committee (EC) has been obtained, after having been duly informed of the nature of their illness and voluntarily accepted treatment program, while being fully aware of the potential risks, benefits and any discomfort involved. 2.Patients diagnosed with Asherman's Syndrome grade II, III or IV, in accordance with the criteria set forth by the European Society of Hysteroscopy (ESH) or grade II, III, IV or V according to the European Society for Gynaecological Endoscopy (ESGE) classification, who intend to undergo Assisted Reproductive Treatment (ART) with Single Embryo Transfer (SET) of blastocysts (Day 5/6 of development) once cell therapy for endometrial regeneration has been completed. Note: Exceptionally, cases of double embryo transfer (DET) if clinically indicated. 3.Patients who, prior to study start, plan to undergo ART in a Hormonal Replecement Therapy (HRT) with donated oocytes (fresh or frozen) or own. - In case of own oocytes at least 2 blastocysts (day 5 or 6 of development) euploid, analyzed by PGD, previously vitrified. - In the case of ovodonation, it may be embryos in the blastocyst stage (fresh or previously vitrified embryos) with or without previous PGD. In the case of vitrified ovodonation embryos it will be necessary to have a minimum of 2 vitrified embryos in the blastocyst stage to meet the inclusion criteria In accordance with standard clinical practice, Pre-implantation Genetic Diagnosis (PGD) is indicated, in compliance with current legislation on human assisted reproductive techniques (Law 14/2006 of May 26). The most common indications for PGD are as follows: Advanced maternal age (age = 36 years), recurring implantation failure, repeated miscarriages or alterations in karyotype of one or both parents as well as any detected in the FISH of sperm cellsor for other reasons that are considered medically indicated. 4.Women of child-bearing potential between 18 and 44 years (both included). 5.BMI: 18 – 30 Kg/m2 (both included). 6.Adequate liver and kidney function, defined as follows: Total bilirubin 1.0 mg/dL, then estimated glomerular filtration rate (eGFR) should be > 60 mL/min/1.73 m2. 7.Absence of severe heart disease. 8.Negative blood pregnancy test. 9.ECOG= 0-1. 10.Negative HIV, HCV, HbsAg, HBcAg and Syphilis tests (recent, at least 30 days). 11.Normal coagulation study. 12.Adequate peripheral venous access. Otherwise, the investigator will assess whether central venous catheter should be implanted. 13.Absence of severe psychiatric illnesses. 14.Patient can adhere to and follow study procedures and checkups, that is, patients who are able to understand and comply with parameters as indicated in the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 22 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Patient refuses to receive central venous catheter as proposed by the investigator in cases where there is no peripheral venous access. 2.Patients who are allergic to iodine contrast. 3.Patients for whom an optimal investigational medicinal product cannot be obtained or infused after performing apheresis and selection. The product is unusable if any of the following mimimun quality criteria are identified: Minimum dose to be perfused lower than 30x106 CD133+. (Note: If the PEI meets the rest of the quality requirements to be perfused, the patient may receive treatment with IGX1 even though the dose is lower than the minimum indicated. The results of this patient will not be included in the Population by protocol, but they can be included for the rest of the population groups). viability lower than 50%. Less than 70% purity. Non-sterile. 4.Patients who have participated in another clinical trial or who have received an investigational treatment in the 30 days prior to the study, unless expressly approved by the sponsor. 5.Existence of severe or uncontrolled bacterial, fungal or viral infections, which in the opinion of the Principal Investigator may interfere with patient’s participation in the study or with the evaluation of the study results. 6.Any illness or medical condition that is unstable or which may put at risk the patient’s safety and her compliance in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess safety and tolerability of the IGX1 investigational medicinal product (CD133+ cells screened after mobilization and collection of peripheral blood progenitor cells (PBPCs) from the same patient) in improving post-treatment reproductive prognosis, as measured by: 1. Identification of incidence, prevalence and frequency of different adverse events that may occur in the patient throughout the study up until Month 15 post-treatment. 2. In the event of a term pregnancy, identification of incidence, prevalence and frequency of different adverse events that may occur during the pregnancy, birth and puerperal period. 3. In case of a Live Birth (LB), identification of incidence, prevalence and frequency of the different adverse events that may be associated with the investigational medicinal product (IMP) until the first month of age.;Secondary Objective: -Efficacy of the investigational medicinal product IGX1 in improving post-treatment reproductive prognosis -Pregnancy follow-up, evaluated by live birth rate (LBR), rate of (clinical and biochemical) miscarriage and rate of ectopic pregnancy from embryo transfer until birth. -Recovery of endometrial volume -Analysis of endometrial vascularization via pre- and post-treatment endometrial biopsy -To evaluate reappearance of menstrual episodes or compare differences in duration and quantity of episodes after treatment until embryo transfer, with respect to menstrual episodes occurring prior to treatment -To determine the cell dose, cut-off point of CD133+ cells needed to discriminate between pregnancy/non-pregnancy according to the minimum quality requirements established -To evaluate and describe quality of life (QoL) of participating patients, using the 2008 FertiQoL International tool;Primary end point(s): oAdverse events (list) at each checkup/medical visit from the instillation with IGX1 until month 1 of the LB (if applicable). oPeriod of time between instil | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): oPregnancy YES/NO, categorical variable oImplantation YES/NO, categorical variable oPregnancy in progress YES/NO, categorical variable oLive birth (LB) YES/NO, categorical variable oHysteroscopic score according to ESH/ESGE (numerical variable) before and after treatment oEndometrial thickness in mm (numerical variable) before and after treatment and at each visit oEndometrial pattern (trilaminar/diffuse), categorical variable before and after treatment and at each visit oPregnancy outcome (categorical list: Pregnancy in progress, clinical or biochemical miscarriage, ectopic pregnancy) oMeasurement of endometrial volume by 3D ECO before and after treatment (numerical variable) oEndometrial vascularization analysis measured using immunohistochemistry with presence of ?-ASMA expression before and after treatment and at each visit oFrequency of menstrual episodes in days (numerical variable) Before and during 6 consecutive months following treatment if any (if patient becomes pregnant prior to this, then they will not be performed) oDuration of menstrual episodes (numerical variable) Before and during 6 consecutive months following cell instillation oNumber of sanitary napkins/day before treatment and during 6 consecutive months following treatment (numerical variable) oNumber of CD133+ cells, explanatory variable (quantitative) oEvolution of quality of life before and after treatment (quantitative and qualitative variable);Timepoint(s) of evaluation of this end point: All secondary variables will be evaluated 15 months after cell therapy except: The hysteroscopic score that will be evaluated on day 35 and the number of CD133 + cells that will be evaluated on day 7. | — |
Countries
Spain
Contacts
Public ContactCarlos Gomez De la Cruz
Asherman Therapy, S.L.U.
Outcome results
None listed