Ovarian Stimulation Single Injection Elonva (OSSIE)

June 19, 2017 updated by: Professor Kelton Tremellen, Flinders Fertility

Ovarian Stimulation Single Injection Elonva- The OSSIE Study

We would like to propose that it may be possible to use a solitary dose of Elonva (corifollitrophin alpha) as the sole gonadotrophin (FSH) stimulant for the vast majority of women undergoing IVF, assuming that it is possible that "coasting" (withholding short acting rFSH) from day 8 of the stimulation until trigger/ oocyte retrieval will still result in a significant number of mature oocytes being produced and an acceptable pregnancy rate.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Elonva (corifollitrophin alfa) has been shown to be a very effective rFSH stimulant for Controlled Ovarian Hyperstimulation (COH) in the setting of IVF treatment. Its long duration of action (7 days) results in a significant reduction in the number of COH stimulation injections (average of 3 injections v 9 injections in the traditional "short acting" r FSH COH), with 30% of patients requiring only a single Elonva injection for their COH (Engage study, Devroey et al 2009). It is assumed that a reduction in the number of required COH injections will have the advantages of improved patient acceptability and better compliance due to a reduction in room for error. Despite these advantages the clinical uptake of Elonva has been slow due to 2 principal concerns among clinicians:

  1. A tendency for Elonva COH to result in a higher ovarian response with increased risk of Ovarian Hyper-Stimulation Syndrome (OHSS). While this risk of OHSS was not statistically significant in the pivotal Engage study, there was still a numerically greater chance of OHSS and a greater chance of the IVF cycle being cancelled due to OHSS risk in the Elonva arm compared to the traditional Puregon arm. Since women at high risk of OHSS were excluded from the Engage study, clinicians perceive that the risk of OHSS is likely to be significantly greater in the more heterogeneous general clinical population. Whether this is a correct assumption is still up for debate, but it is a perceived issue with the existing Elonva protocol that must be addressed if Elonva is to become used widely as a COH stimulant.
  2. According to the Engage and Ensure studies, the majority (70%) of women using Elonva require "top up"short acting Puregon rFSH, with an average of 2 doses being required before the patients reach the criteria for triggering and oocyte retrieval. As a result clinics are required to teach two different injection protocols, increasing the time required to educate the patient and possibly increasing the risk of confusion. The ability to deliver a solitary COH stimulant without the need for any "top up" Puregon would be a major advantage.

Rationale We would like to propose that it may be possible to use a solitary dose of Elonva as the sole COS rFSH stimulant for the vast majority of women undergoing IVF, assuming that it is possible that "coasting" (withholding short acting rFSH) from day 8 of the stimulation until trigger/ oocyte retrieval will still result in a significant number of mature oocytes being produced.

In the setting of OHSS it is common practice to withhold any further rFSH stimulant towards the end of the COS process. It is generally accepted that medium size follicles of 14 mm or greater will continue to develop to maturity in the absence of rFSH stimulation, while smaller follicles will regress. This has the therapeutic advantage of reducing estradiol levels and OHSS risk in women at high risk of OHSS. With this coasting physiology in mind, we propose that provided a single injection of Elonva can result in a significant number of follicles being 14 mm or greater by day 8 of stimulation, further rFSH will not be required. Results from the Engage study (Doody et al 2011) reveal that by day 8 of stimulation on average there were 5.1 follicles of 15 mm or greater. Therefore even if no further "top up" rFSH was given from day 8, one could expect to get at least 5 mature oocytes from an oocyte retrieval triggered by hCG in the next 2 days. While 5 mature oocytes is significantly less than what was produced by the traditional Elonva protocol using additional rFSH (average 10.8 in the Engage study, 10.7 in the Ensure study), this could be perceived as a significant advantage since it will likely result in a significant reduction in OHSS risk, a perceived problem with the traditional Elonva protocol. If we assume a 70% fertilization rate and that approximately half of all embryos are of good quality by day 4/5 of culture, the production of > 3 mature oocytes should ensure the generation of at least one good quality embryo for transfer with a good chance of pregnancy. This type of low impact stimulation is likely to be very popular in Europe and Australia where clinicians already accept the benefits of mild COS.

In summary, if we are able to provide evidence in this pilot study that a single injection of Elonva can result in the majority of women reaching oocyte retrieval with the production of at least 3 mature oocytes, while giving good fresh embryo transfer pregnancy rates and no OHSS, the coasting Elonva protocol may become a significant clinical protocol for low impact COS in the future.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Fertility

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 33 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Undergoing a GnRH antagonist cycle of IVF as part of their personal fertility treatment
  • Eligible for the use of the 150 mcg dose of Elonva according to Australian PBS requirements (weight > 60 kg, antral follicle count < 20)
  • Intention of undergoing a fresh embryo transfer.
  • No major sperm quality issues (ejaculate sperm concentration > 5 million/ ml, motility > 25% neat sample). ICSI for the indication of poor morphology would be acceptable for trial enrollment.
  • Maternal age 18-37 years inclusive.

Exclusion Criteria:

  • Low ovarian reserve (antral follicle count 2-10 mm < 7, early follicular phase FSH > 10 IU/L, < 4 oocytes prior IVF cycle on a dose of rFSH > 150 IU).
  • Ovarian pathology (PCOS, ovarian cyst, endometrioma, poor trans-vaginal ultrasound ovary access).
  • 2 or more previous cycles of IVF (stimulated cycles) in which a live birth pregnancy did not result, or one prior stimulated cycle of IVF and 2 or more frozen embryo transfer cycles without a live birth outcome (possible implantation failure).
  • Significant pelvic pathology likely to impair embryo implantation (fibroids, polyps, uterine septum, hydrosalpinx).
  • Intention to freeze all embryos with nil fresh transfer (pre-implantation genetic screening, oncology fertility preservation).
  • Known renal impairment
  • Use of a long down regulation or "flare" IVF protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: corifollitrophin alfa
corifollitrophin alfa used as COH stimulant in IVF
Drug: corifollitrophin alfa
use of a single dose of corifollitrophin alfa to provide adequate controlled ovarian hyperstimulation during IVF treatment
Other Names:
  • Elonva

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Oocyte maturity - number of mature oocytes (metaphase II oocytes) retrieved in IVF cycle
Time Frame: IVF cycle (2 weeks approximately)
number of mature oocytes (metaphase II oocytes) retrieved in IVF cycle
IVF cycle (2 weeks approximately)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
cryopreservation of embryos - number of good quality embryos available for cryopreservation
Time Frame: IVF cycle
number of good quality embryos available for cryopreservation
IVF cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Flinders Fertility

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Flinders University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Kelton Tremellen, MD PhD, Flinders University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 8, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 13, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 21, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 19, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AU/1/2 C8B110

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Infertility

Clinical Trials on corifollitrophin alfa

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings