InfertilityPhase 3NCT01121991
A Prospective Study to Evaluate the Addition of Subcutaneous Recombinant Human-Luteinizing Hormone With Recombinant Human-Follicle Stimulating Hormone on Follicular Development in Women Undergoing Ovarian Stimulation for Assisted Reproductive Technologies
A Phase 3 study testing Recombinant Human-Luteinizing Hormone (Luveris) in people with Infertility and Ovarian Stimulation, run by EMD Serono.
Trial summary
In-vitro fertilization (IVF) of human oocytes followed by the replacement of embryo in the uterine cavity has become a well established treatment for female infertility attributable to damaged fallopian tubes, endometriosis or unexplained causes where alternative forms of therapy have failed. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Infertility, Ovarian Stimulation
- What is being tested?
- Recombinant Human-Luteinizing Hormone (Luveris)
- Type of treatment
- Injection or infusion
- How many people
- 55 participants
- Where
- No sites listed yet
- Study dates
- Sep 2004to Sep 2005
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Female subjects who underwent ovarian stimulation for ART (IVF/ICSI) using r-hFSH.
- Subjects who in the opinion of the treating investigator met any of the following criteria to require r-LH supplementation during the ovarian stimulation:
- were selected for a GnRH agonist protocol to induce pituitary desensitization
- previous poor ovarian response to r-hFSH alone
- aged 35 to 40 years
- elevated baseline hormone parameters that were predictive of poor ovarian response
Show all 11Show fewer
- Female subjects aged between 18-40 years
- Subjects with uterine cavity able to sustain embryo implantation or pregnancy
- Subject who had no known infection with human immunodeficiency virus, hepatitis B or C virus
- Subjects who were willing to participate and comply with the protocol for the duration of the study
- Subjects who had given informed consent, prior to any study-related procedure not part of normal medical care
Who cannot join
- Subjects with clinically significant systemic disease (e.g. insulin-dependent diabetes, epilepsy, severe migraine, intermittent porphyria, hepatic, renal or cardiovascular disease, severe corticosteroid-dependent asthma)
- Any contraindication to being pregnant and/or carrying a pregnancy to term
- Subjects with abnormal gynecological bleeding of undetermined origin
- Subjects with known allergy to gonadotrophin preparations
- Subjects with any medical condition for which the use of gonadotrophin preparations was contraindicated
- Subjects who had previously entered into this study or simultaneously participated in another clinical drug trial
- Subjects with any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years
- Subjects who had refused or were unable to comply with protocol
About this study
Official title: A Phase III, Multicentre, Open-label Prospective Study to Evaluate the Addition of Subcutaneous Recombinant Human-Luteinizing Hormone (Luveris) With r-hFSH on Follicular Development in Women Undergoing Ovarian Stimulation for ART
In-vitro fertilization (IVF) of human oocytes followed by the replacement of embryo in the uterine cavity has become a well established treatment for female infertility attributable to damaged fallopian tubes, endometriosis or unexplained causes where alternative forms of therapy have failed. The most commonly used protocols of follicular stimulation now employs follicle stimulating hormone (FSH) and long-acting agonists of gonadotropin releasing hormone (GnRH) to prevent the occurrence of a mid-cycle luteinizing hormone (LH) surge and to ensure the induction of well-synchronized larger cohort of ovarian follicles.
The results of a number of studies have demonstrated that in the majority of clinical situations, FSH administration alone is sufficient to achieve successful follicular development. A study had shown that in subjects receiving recombinant human-follicle stimulating hormone (r-hFSH) and recombinant human-luteinizing hormone (r-hLH), pregnancy rates were similar in the younger and older age groups, however, in women receiving r-hFSH alone, there was a significant decline in pregnancy rates for women 35 and older. This particular study also went on to show that the subgroup of women 35 and older, may benefit from supplementary r-hLH. A number of studies have been conducted to assess the safety and efficacy of r-hLH administered concomitantly with r-hFSH in the presence of developing follicles to reduce the rate of growth of intermediate and small follicles while allowing the dominant follicle to continue to progress.
This was a Phase III, open-label, multicentre study to evaluate safety and efficacy of addition of Recombinant Human-Luteinizing Hormone (Luveris) to a standard assisted reproductive technologies (ART) protocol.
Read the detailed description
Luteinizing hormone is a heterodimeric glycoprotein composed of a non-covalent association of an α and a β subunit. Prior to the generation of human-LH (hLH) through recombinant technology, hLH had only been available for therapeutic use as human menopausal gonadotropins (hMG), a co-extracted, purified preparation of hLH and hFSH from urine of post menopausal women. Recombinant Human-Luteinizing Hormone (Luveris) has been found to be well tolerated in human pharmacokinetic and pharmacodynamic studies at doses of up to 40,000 IU in healthy female volunteers without any Serious Adverse Event (SAE) experience being reported.
OBJECTIVES
- To evaluate safety and efficacy of addition of Recombinant Human-Luteinizing Hormone (Luveris) to a standard ART procedure.
In this study, subjects were first treated with a GnRH agonist to induce pituitary desensitization according to centre's standard practice followed by administration of r-hFSH. All subjects were then treated with Recombinant Human -Luteinizing Hormone (Luveris)150 IU per day subcutaneous (s.c.) from Day 6 of stimulation of their ART treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.
- Conditions
- Infertility, Ovarian Stimulation
- Being tested
- Recombinant Human-Luteinizing Hormone (Luveris)
- Keywords
- Infertility, Ovarian Stimulation, Luveris, Lutropin alpha, Controlled ovarian stimulation, Reproductive techniques, assisted
- Medical subject headings
- Infertility, Helping Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Human-Luteinizing Hormone (Luveris)Drug
Recombinant Human-Luteinizing Hormone (Luveris) was administered once daily subcutaneously at a starting dose of 150 IU per day beginning on stimulation Day 6.
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Number of Metaphase II Oocytes Per Participant Who Underwent Ovum Pick up for Intra-cytoplasmic Sperm Injection (ICSI)
Mean number of metaphase II oocytes was calculated for each participant undergoing ovum pick up for ICSI. ICSI is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. Metaphase II stage of the oocyte was classified as the time at which the first polar body was observed microscopically. Metaphase II oocytes are a sub-group of the total number of oocytes.
Measured: On the day of ovum pick up (Day 1 or 2 after human chorionic gonadotropin [hCG] administration).
Mean Number of Mature Oocytes Per Participant Who Underwent Ovum Pick up for In Vitro Fertilization (IVF)
Mean number of oocytes undergoing ovum pick up for IVF were calculated for each participant. IVF is a process by which egg cells are fertilized by sperm outside the body, in-vitro.
Measured: On the day of ovum pick up (Day 1 or 2 after hCG administration).
Secondary outcomes (6)
Mean Number of Oocytes Retrieved Per Number of Follicles Aspirated on the Day of Ovum Pick up
Mean number of oocytes retrieved per number of follicles aspirated on the day of ovum pick up was calculated. Oocyte retrieval is a technique used in in vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.
Measured: On day of ovum pick up (Day 1 or 2 after hCG administration)
Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies
Biochemical pregnancy: A positive pregnancy test defined as hCG level >10 IU/L in a sample taken at least 14 days after Day 3 embryo transfer or 12 days after Day 5/6 embryo transfer with no further ultrasound confirmation of the existence of a gestational sac in the uterus. Clinical pregnancy: Existence of at least one ultrasonography confirmed gestational sac in the uterus, with or without heartbeat.
Measured: Post-hCG days 15-20 and post-hCG days 35-42.
Number of Participants With Multiple Pregnancies
Multiple pregnancy is a pregnancy where more than one fetus develops simultaneously in the womb. There are two types of twinning-identical and fraternal. Identical twins represent the splitting of a single fertilized zygote (union of two gametes or male/female sex cells that produce a developing fetus) into two separate individuals.
Measured: Post-hCG Day 35-42.
Number of Live Births
A live birth occurs when a fetus, whatever its gestational age, exits the maternal body and subsequently shows any sign of life, such as voluntary movement, heartbeat, or pulsation of the umbilical cord, for however brief a time and regardless of whether the umbilical cord or placenta are intact.
Measured: Post-hCG days 15-20 to pregnancy follow up.
Pregnancy Loss Per Clinical Pregnancy
Preclinical miscarriage: Spontaneous cessation of a biochemical pregnancy. Early spontaneous abortion: Any spontaneous abortion occurring after confirmation of clinical pregnancy and before completion of 12 weeks of gestation. Late spontaneous abortion: any spontaneous abortion occurring between completion of 12 weeks of gestation and prior to a viable stage. Pregnancy loss per clinical pregnancy was measured as a percentage.
Measured: Post-hCG days 35-42.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation.
AEs: Any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. TEAEs: AEs that occur during treatment with the study drug. It also included incidences of mild, moderate and severe ovarian hyperstimulation syndrome (OHSS). SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued from the study due to AE were also recorded.
Measured: From stimulation Day 1 (S1) to post-hCG days 35-42 (safety visit).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2010 (estimated)
- Study startSep 2004
- Primary completionSep 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Medical Responsible, Study director, EMD Serono Canada Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01121991
- Sponsor's protocol ID
- IMP 25244
- Status last verified
- Aug 2013
- First submitted
- 10 May 2010
- Last updated
- 7 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicentre, Open-label Prospective Study to Evaluate the Addition of Subcutaneous Recombinant Human-Luteinizing Hormone (Luveris) With r-hFSH on Follicular Development in Women Undergoing Ovarian Stimulation for ART
- ClinicalTrials.gov ID
- NCT01121991
- Acronym / sponsor ID
- IMP 25244
- Conditions
- Infertility, Ovarian Stimulation
- Keywords
- Infertility, Ovarian Stimulation, Luveris, Lutropin alpha, Controlled ovarian stimulation, Reproductive techniques, assisted
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Study start
- Sep 2004
- Primary completion
- Sep 2005 (actual)
- First posted
- 12 May 2010 (estimated)
- Results
- Posted 18 Mar 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In-vitro fertilization (IVF) of human oocytes followed by the replacement of embryo in the uterine cavity has become a well established treatment for female infertility attributable to damaged fallopian tubes, endometriosis or unexplained causes where alternative forms of therapy have failed. The most commonly used protocols of follicular stimulation now employs follicle stimulating hormone (FSH) and long-acting agonists of gonadotropin releasing hormone (GnRH) to prevent the occurrence of a mid-cycle luteinizing hormone (LH) surge and to ensure the induction of well-synchronized larger cohort of ovarian follicles.
The results of a number of studies have demonstrated that in the majority of clinical situations, FSH administration alone is sufficient to achieve successful follicular development. A study had shown that in subjects receiving recombinant human-follicle stimulating hormone (r-hFSH) and recombinant human-luteinizing hormone (r-hLH), pregnancy rates were similar in the younger and older age groups, however, in women receiving r-hFSH alone, there was a significant decline in pregnancy rates for women 35 and older. This particular study also went on to show that the subgroup of women 35 and older, may benefit from supplementary r-hLH. A number of studies have been conducted to assess the safety and efficacy of r-hLH administered concomitantly with r-hFSH in the presence of developing follicles to reduce the rate of growth of intermediate and small follicles while allowing the dominant follicle to continue to progress.
This was a Phase III, open-label, multicentre study to evaluate safety and efficacy of addition of Recombinant Human-Luteinizing Hormone (Luveris) to a standard assisted reproductive technologies (ART) protocol.
Detailed description
Luteinizing hormone is a heterodimeric glycoprotein composed of a non-covalent association of an α and a β subunit. Prior to the generation of human-LH (hLH) through recombinant technology, hLH had only been available for therapeutic use as human menopausal gonadotropins (hMG), a co-extracted, purified preparation of hLH and hFSH from urine of post menopausal women. Recombinant Human-Luteinizing Hormone (Luveris) has been found to be well tolerated in human pharmacokinetic and pharmacodynamic studies at doses of up to 40,000 IU in healthy female volunteers without any Serious Adverse Event (SAE) experience being reported.
OBJECTIVES
- To evaluate safety and efficacy of addition of Recombinant Human-Luteinizing Hormone (Luveris) to a standard ART procedure.
In this study, subjects were first treated with a GnRH agonist to induce pituitary desensitization according to centre's standard practice followed by administration of r-hFSH. All subjects were then treated with Recombinant Human -Luteinizing Hormone (Luveris)150 IU per day subcutaneous (s.c.) from Day 6 of stimulation of their ART treatment cycle, continuing at the same dose until injection of hCG upto and including day of last FSH dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Female subjects who underwent ovarian stimulation for ART (IVF/ICSI) using r-hFSH.
- Subjects who in the opinion of the treating investigator met any of the following criteria to require r-LH supplementation during the ovarian stimulation:
- Female subjects aged between 18-40 years
- Subjects with uterine cavity able to sustain embryo implantation or pregnancy
- Subject who had no known infection with human immunodeficiency virus, hepatitis B or C virus
Key exclusion criteria (8 listed)
- Subjects with clinically significant systemic disease (e.g. insulin-dependent diabetes, epilepsy, severe migraine, intermittent porphyria, hepatic, renal or cardiovascular disease, severe corticosteroid-dependent asthma)
- Any contraindication to being pregnant and/or carrying a pregnancy to term
- Subjects with abnormal gynecological bleeding of undetermined origin
- Subjects with known allergy to gonadotrophin preparations
- Subjects with any medical condition for which the use of gonadotrophin preparations was contraindicated
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant Human-Luteinizing Hormone (Luveris)Recombinant Human-Luteinizing Hormone (Luveris) was administered once daily subcutaneously at a starting dose of 150 IU per day beginning on stimulation Day 6. | Drug | – |
Primary outcome
Mean Number of Metaphase II Oocytes Per Participant Who Underwent Ovum Pick up for Intra-cytoplasmic Sperm Injection (ICSI)
Time frame: On the day of ovum pick up (Day 1 or 2 after human chorionic gonadotropin [hCG] administration).
Mean number of metaphase II oocytes was calculated for each participant undergoing ovum pick up for ICSI. ICSI is an in-vitro fertilization procedure in which a single sperm is injected directly into an egg under a microscope. Metaphase II stage of the oocyte was classified as the time at which the first polar body was observed microscopically. Metaphase II oocytes are a sub-group of the total number of oocytes.
Mean Number of Mature Oocytes Per Participant Who Underwent Ovum Pick up for In Vitro Fertilization (IVF)
Time frame: On the day of ovum pick up (Day 1 or 2 after hCG administration).
Mean number of oocytes undergoing ovum pick up for IVF were calculated for each participant. IVF is a process by which egg cells are fertilized by sperm outside the body, in-vitro.
6 secondary outcomes
Mean Number of Oocytes Retrieved Per Number of Follicles Aspirated on the Day of Ovum Pick up
Time frame: On day of ovum pick up (Day 1 or 2 after hCG administration)
Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies
Time frame: Post-hCG days 15-20 and post-hCG days 35-42.
Number of Participants With Multiple Pregnancies
Time frame: Post-hCG Day 35-42.
Number of Live Births
Time frame: Post-hCG days 15-20 to pregnancy follow up.
Pregnancy Loss Per Clinical Pregnancy
Time frame: Post-hCG days 35-42.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Study Drug Discontinuation.
Time frame: From stimulation Day 1 (S1) to post-hCG days 35-42 (safety visit).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono Canada Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Recombinant Human-Luteinizing Hormone (Luveris) in people with Infertility and Ovarian Stimulation, run by EMD Serono.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Mar 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Number of Metaphase II Oocytes Per Participant Who Underwent Ovum Pick up for Intra-cytoplasmic Sperm Injection (ICSI) (time frame: On the day of ovum pick up (Day 1 or 2 after human chorionic gonadotropin [hCG] administration).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2013.