E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
In vitro fertilization include controlled ovarian stimulation (COS), where
follicles are stimulated to full maturity.
One of the main problems of the IVF treatment is still to some patients
develop a very large number of follicles, and others only a few. A large
number of follicles (eggs) increases the risk of ovarian hyperstimulation
syndrome (OHSS), while few follicles (eggs) reduces the chance of
pregnancy. |
|
E.1.1.1 | Medical condition in easily understood language |
The main problems of IVF treatment is different development of either a
large number of follicles or only a few. |
|
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021930 |
E.1.2 | Term | Infertility NOS |
E.1.2 | System Organ Class | 100000004872 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To show that the group randomized to individual AMH based stimulation
achieves a more homogeneous distribution of the retrieved eggs than
the group receiving standard treatment.
Primary endpoint:
The primary endpoint is an appropriate or an inappropriate number of
oocytes:
This should be understood in the term of patients in the two arms are
classified as having an appropriate response (5 - 14 eggs) or
inappropriate response (<5 or> 14 eggs);
An inappropriate response includes those patients where the treatment
is canceled due to either too few follicles or egg maturation with hCG
omitted due to risk of OHSS (given as GnRH agonist (Suprefact) instead
of) |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Genetic sub-study:
The study will also include a "genetic part" of series of analyzes of both
FSH, AMH and AMH receptor polymorphisms. Among the secondary end -
points we will analyze whether there is a correlation between the
detection of specific single nucleotide polymorphisms and patients'
responses. We have recently shown that two genetic variants of AMH
(Ile49Ser; rs10407022) and its specific type II receptor (AMHR2 -482
A> G, rs2002555) genes are associated with estradiol levels in normally
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ovulating women, suggesting that these gene variants affect FSH
sensitivity of the follicles.
We will further analyze whether there is a correlation between the basal
AMH and proven AMH receptor polymorphisms. It could, for example
conceivable that there was a link between suboptimal functioning AMH
receptor and the basal AMH, so that a dysfunctional AMH system leads to
accelerated loss of ægreserve.
Biostatistics part-study:
This part will be using biostatistical modeling to analyze recruitment and
maturation of antral follicles in order: What factors are the primary
determinants of the percentage of registered antral follicles are
recruited and mature. Follicular growth and endocrine responses will be
carefully and frequently monitored.
|
|
E.3 | Principal inclusion criteria |
- Women with evidence of COS a view IVFeller ICSI
- First treatment with IVF / ICSI in the department
- Age between 25-38 years;
- AMH is between 5-50
- Weight <75kg
- Normal menstrual cycle length of 24 to 35 days, which are presumably
ovulatory;
- Two ovaries;
- Uterus with expected normal function (eg. No clinically significant
fribromer) documented by ultrasound at screening;
- Willing and able to sign the informed consent. |
|
E.4 | Principal exclusion criteria |
-History of current PCOS or endometriosis stage III / IV
-History of severe ovarian hyperstimulation syndrome;
- Presence of hydrosalpinx by ultrasound;
- History of recurrent consecutive miscarriages (> 3)
-FSH> 12 IU / L (in the early follicular phase);
- Contraindications for use of gonadotropins or GnRH analogues;
-History of current epilepsy, HIV infection, diabetes or cardiovascular,
gastrointestinal, hepatic, renal, or pulmonary disease;
- Pregnancy, lactation or contraindication to pregnancy;
- Current or previous (last 12 months) abuse of alcohol or drugs;
- History of chemotherapy (except gestationelle reasons) and
radiotherapy;
- Undiagnosed vaginal bleeding;
- Tumors of the ovary, breast, adrenal, pituitary or hypothalamus and
malformations of sexual organs incompatible with pregnancy;
- Abnormal karyotype of the patient (if karyotype is performed);
- Hypersensitivity to study drug. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint
The primary endpoint is an appropriate or an inappropriate number of
oocytes:
This should be understood so that the patients in the two arms are
classified as having an appropriate response (5 - 14 eggs) or
inappropriate response (<5 or> 14 eggs);
An inappropriate response includes those patients where the treatment
is canceled due to either too few follicles or egg maturation with hCG
omitted due to risk of OHSS (given as GnRH agonist (Suprefact) instead
of) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Timepoint of endpoint for the primary endpoint is Marts 2016 |
|
E.5.2 | Secondary end point(s) |
-fertilization rate
-Number transferede embryos
- Number of patients who achieve blastocyst transfer ring
- implantation rate
- Duration of stimulation
- Luteal phase inconvenience and enlargemen of ovaries
- Clinical pregnancy (GA weeks 7-8) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timpoint will be Dec 2016 due to pregnancy at last patient |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
"End of study" is when a pregnancy is categorized as ongoing ie.
continue beyond 7 weeks at the last patient
Within 90 days after the "End Study", the regional research ethics
committee and the Danish Medicines Agency will be informed that the
investigation is complete. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |