Ovarian StimulationPhase 2NCT01112358

Lutropin Alfa in Women at Risk of Poor Response

A Phase 2 study testing r-FSH, r-hLH and Analogous GnRH antagonist in people with Ovarian Stimulation, run by Merck KGaA, Darmstadt, Germany at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages Up to 38 years, women only
Conditions the study is for: Ovarian Stimulation
What is being tested?: r-FSH, r-hLH and Analogous GnRH antagonist
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 58 participants
Where: 1 siteSpain
Study dates: 7 Dec 2005to 30 Jan 2007
Phase: Phase 2
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 Up to 38 years
Women only
No healthy volunteers
Child, Adult

Who may be able to join

Participants who were at risk of poor response by at least one of the following criteria: a) <3 follicles in last cycle, or less than or equal to (</=) 2 metaphase II oocytes, or estradiol (E2) <600 pg/mL; b) Cancellation of previous cycle; c) Early follicular serum Follicle-Stimulating Hormone (FSH) >8.5 milli IU/L
Participants with normal baseline luteinizing hormone and E2 levels
Regular menstrual cycles of 25-35 days
Presence of both ovaries and uterus able to withstand pregnancy

Who cannot join

Participants who had any clinically significant disease including known human immunodeficiency virus (HIV), hepatitis-B virus (HBV)/hepatitis-C virus (HCV) positivity
Participants with more than 3 previous assisted reproductive techniques (ART) cycles
Participants with polycystic ovaries or cyst of unknown etiology; unexplained gynecological bleeding
Participants who had any contraindication to being pregnant
Active substance abuse
Participants who had simultaneously participated in another clinical drug trial

Trial locations and contacts

1 site in 1 country.

Spain1 site

Hospital Universitario de La Fe
Valencia

Other trials in Spain

About this study

Official title: Lutropin Alfa (Luveris®) in Women at Risk of Poor Response Suppressed With Cetrorelix: an Exploratory Trial

Evaluate the effectiveness of adding lutropin alfa (recombinant human luteinizing hormone [r-hLH]) in the middle of the follicular phase compared to no addition, in infertile women at risk of poor response stimulated with follitropin alfa (recombinant Follicle-Stimulating Hormone [r-FSH]) under Gonadotropin Releasing Hormone (GnRH) antagonist in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), in the number and quality of oocytes, follicular development, fertilization oocyte, embryo quality, and pregnancy rate.

Conditions: Ovarian Stimulation
Being tested: r-FSH, r-hLH, Analogous GnRH antagonist, r-hCG, Progesterone
Keywords: Lutropin alfa, Fertilization in vitro, Intracytoplasmic sperm injection, Reproductive techniques, assisted
Medical subject headings: Helping Behavior

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

r-FSHDrug
Also called Follitropin alfa; Gonal-F®
r-FSH will be administered as specified in the arm description.
r-hLHDrug
Also called Lutropin alfa; Luveris®
r-hLH will be administered as specified in the arm description.
Analogous GnRH antagonistDrug
Also called Cetrotide®
Analogous GnRH antagonist will be administered as specified in the arm description.
r-hCGDrug
r-hCG will be administered as specified in the arm description.
ProgesteroneDrug
Progesterone will be administered as specified in the arm description.

Study groups in NCT01112358
Study group	Role	What they receive
r-FSH + r-hLH	Experimental	Lutropin alfa (r-hLH) will be administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (r-FSH) will be administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose will then be adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants will also receive analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) will be administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist. Receives: Drug: r-FSH; Drug: r-hLH; Drug: Analogous GnRH antagonist; Drug: r-hCG; Drug: Progesterone
r-FSH	Active comparator	Follitropin alfa (r-FSH) will be administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose will then be adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants will also receive analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG will be administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist. Receives: Drug: r-FSH; Drug: Analogous GnRH antagonist; Drug: r-hCG; Drug: Progesterone

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Oocytes Retrieved
Measured: At the end of stimulation (Day 2 up to Day 8)
Number of Follicles Greater Than (>) 14 Millimeter (mm) in Diameter
Measured: At the end of stimulation (Day 2 up to Day 8)
Oocytes Recovery Rate
Oocytes recovery rate (oocytes per >14 mm follicle) is defined as number of oocytes retrieved divided by number of follicles >14 mm in diameter.
Measured: At the end of stimulation (Day 2 up to Day 8)

Secondary outcomes (13)

Oocyte Nuclear Maturity Rate
Oocyte nuclear maturity rate (metaphase II oocytes per retrieved oocyte) is defined as number of metaphase II oocytes divided by total number of oocytes retrieved.
Measured: At the end of stimulation (Day 2 up to Day 8)
Fertilization Rate
The fertilization rate (2 pronuclei [PN] fertilized oocytes per inseminated oocyte) was defined as number of 2 PN fertilized oocytes divided by number of inseminated oocytes.
Measured: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Embryos by Quality
Embryo quality was graded according to morphological classification of Veeck. Grade 1: even blastomeres with no fragmentation; Grade 2: even blastomeres with slight fragmentation (less than 20%); Grade 3: uneven size blastomeres with no fragmentation; Grade 4: even or uneven size blastomeres with moderate fragmentation (20-25%); and Grade 5: unrecognizable blastomeres with severe fragmentation (>50%).
Measured: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Embryos Transferred by In Vitro Fertilization (IVF)
Measured: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Participants With Positive Pregnancy Test
The beta Human Chorionic Gonadotropin (beta-hCG) test was used as pregnancy test.
Measured: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Participants With Clinical Pregnancy
A clinical pregnancy is a pregnancy that is confirmed by both pregnancy test (beta-hCG test) and sonographic confirmation of a gestational sac or heartbeat (fetal sac).
Measured: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Implementation Rate
Implementation rate (clinical pregnancy/embryo transferred) was defined as the number of clinical pregnancies divided by number of embryos transferred.
Measured: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Plasma Level of Estradiol
Measured: At the time of r-hCG administration (any days between Day 2 to Day 8)
Endometrial Thickness
Measured: At the time of r-hCG administration (any days between Day 2 to Day 8)
Duration of Ovarian Stimulation
Duration of ovarian stimulation was defined as the time from start of study treatment to time of r-hCG administration.
Measured: Randomization to Day 8
rFSH Cumulative Dose
Measured: Randomization to Day 8
Plasma Levels of LH
Measured: At the time of r-hCG administration (any days between Day 2 to Day 8)
Number of Participants in Whom At Least 1 Stimulation Cycle Was Cancelled
Measured: Randomization to Day 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Dec 200530 Jan 2007

First posted28 Apr 2010 (estimated)
Study start7 Dec 2005
Primary completion30 Jan 2007
Study completion30 Jan 2007

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Ovarian StimulationStudies 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01112358
Sponsor's protocol ID: IMP26170 (INI25954)
Other IDs: 2005-002229-30, 2005
Status last verified: Jul 2018
First submitted: 26 Apr 2010
Last updated: 28 Aug 2018
Results posted: Yes, on ClinicalTrials.gov

Publications

M.J. Fernández Ramírez, A. Monzó, T. García-Gimeno, J.M. Rubio, V. Montañana, C. Duque, G. Herrero, A. Romeu. Role of LH administration during the follicullar phase in women with risk of low response in ovarian stimulation with FSH and cetrorelix for IVF, REVISTA IBEROAMERICANA DE FERTILIDAD, Vol. 23- nº 5 - Septiembre-Octubre 2006

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Active, not recruitingPhase 1/2
Opt-IVF for Personalized Medicine for Normal Responders
Ivf
Recruiting
Trigger Timing in Ovarian Stimulations
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All Ovarian Stimulation trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Lutropin Alfa (Luveris®) in Women at Risk of Poor Response Suppressed With Cetrorelix: an Exploratory Trial
ClinicalTrials.gov ID: NCT01112358
Acronym / sponsor ID: IMP26170 (INI25954)
Conditions: Ovarian Stimulation
Keywords: Lutropin alfa, Fertilization in vitro, Intracytoplasmic sperm injection, Reproductive techniques, assisted
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 58 participants (actual)
Lead sponsor: Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: 7 Dec 2005 (actual)
Primary completion: 30 Jan 2007 (actual)
Study completion: 30 Jan 2007 (actual)
First posted: 28 Apr 2010 (estimated)
Results: Posted 30 Jul 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
r-FSH + r-hLH	Experimental	Drug: r-FSH, Drug: r-hLH, Drug: Analogous GnRH antagonist, Drug: r-hCG, Drug: ProgesteroneLutropin alfa (r-hLH) will be administered at a daily dose of 150 International Units (IU) from the presence of at least one follicle greater than (>) 14 millimeter (mm) to complete ovarian stimulation. Follitropin alfa (r-FSH) will be administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose will then be adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants will also receive analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 milligrams (mg) of recombinant Human Chorionic Gonadotropin (r-hCG) will be administered subcutaneously at 12 hours after the last injection of lutropin alfa and/or follitropin alfa and analogous GnRH antagonist.
r-FSH	Active comparator	Drug: r-FSH, Drug: Analogous GnRH antagonist, Drug: r-hCG, Drug: ProgesteroneFollitropin alfa (r-FSH) will be administered at an initial dose of 225-450 IU per day (according to standard center practice); the dose will then be adjusted to ovarian response as assessed by ovarian ultrasound and/or serum estradiol. Participants will also receive analogous GnRH antagonist and natural progesterone, as per standard center practice. To complete follicular maturation and trigger ovulation, a single dose of 250 mg of r-hCG will be administered subcutaneously at 12 hours after the last injection of follitropin alfa and analogous GnRH antagonist.

Who may qualify

Ages: Up to 38 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (4 listed)

Participants who were at risk of poor response by at least one of the following criteria: a) <3 follicles in last cycle, or less than or equal to (</=) 2 metaphase II oocytes, or estradiol (E2) <600 pg/mL; b) Cancellation of previous cycle; c) Early follicular serum Follicle-Stimulating Hormone (FSH) >8.5 milli IU/L
Participants with normal baseline luteinizing hormone and E2 levels
Regular menstrual cycles of 25-35 days
Presence of both ovaries and uterus able to withstand pregnancy

Key exclusion criteria (6 listed)

Participants who had any clinically significant disease including known human immunodeficiency virus (HIV), hepatitis-B virus (HBV)/hepatitis-C virus (HCV) positivity
Participants with more than 3 previous assisted reproductive techniques (ART) cycles
Participants with polycystic ovaries or cyst of unknown etiology; unexplained gynecological bleeding
Participants who had any contraindication to being pregnant
Active substance abuse

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
r-FSHAlso: Follitropin alfa; Gonal-F®r-FSH will be administered as specified in the arm description.	Drug	r-FSH, r-FSH + r-hLH
r-hLHAlso: Lutropin alfa; Luveris®r-hLH will be administered as specified in the arm description.	Drug	r-FSH + r-hLH
Analogous GnRH antagonistAlso: Cetrotide®Analogous GnRH antagonist will be administered as specified in the arm description.	Drug	r-FSH, r-FSH + r-hLH
r-hCGr-hCG will be administered as specified in the arm description.	Drug	r-FSH, r-FSH + r-hLH
ProgesteroneProgesterone will be administered as specified in the arm description.	Drug	r-FSH, r-FSH + r-hLH

Primary outcome

Number of Oocytes Retrieved
Time frame: At the end of stimulation (Day 2 up to Day 8)
Number of Follicles Greater Than (>) 14 Millimeter (mm) in Diameter
Time frame: At the end of stimulation (Day 2 up to Day 8)
Oocytes Recovery Rate
Time frame: At the end of stimulation (Day 2 up to Day 8)
Oocytes recovery rate (oocytes per >14 mm follicle) is defined as number of oocytes retrieved divided by number of follicles >14 mm in diameter.

13 secondary outcomes

Oocyte Nuclear Maturity Rate
Time frame: At the end of stimulation (Day 2 up to Day 8)
Fertilization Rate
Time frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Embryos by Quality
Time frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Embryos Transferred by In Vitro Fertilization (IVF)
Time frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Participants With Positive Pregnancy Test
Time frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Number of Participants With Clinical Pregnancy
Time frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Implementation Rate
Time frame: Up to 35-45 days after administration of r-hCG (r-hCG administration = Day 2 to Day 8)
Plasma Level of Estradiol
Time frame: At the time of r-hCG administration (any days between Day 2 to Day 8)
Endometrial Thickness
Time frame: At the time of r-hCG administration (any days between Day 2 to Day 8)
Duration of Ovarian Stimulation
Time frame: Randomization to Day 8
rFSH Cumulative Dose
Time frame: Randomization to Day 8
Plasma Levels of LH
Time frame: At the time of r-hCG administration (any days between Day 2 to Day 8)
Number of Participants in Whom At Least 1 Stimulation Cycle Was Cancelled
Time frame: Randomization to Day 8

Results and safety

Results posted to the registry on 30 Jul 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
r-FSH + r-hLH	25	25
r-FSH	33	33

Primary outcome: Number of Oocytes Retrieved

Time frame: At the end of stimulation (Day 2 up to Day 8). Mean (Standard Deviation). Unit: Oocytes

Measure	r-FSH + r-hLH n = 25	r-FSH n = 33
Value	4.0 (5.3)	3.5 (3.1)

Population analysed: ITT population

Primary outcome: Number of Follicles Greater Than (>) 14 Millimeter (mm) in Diameter

Time frame: At the end of stimulation (Day 2 up to Day 8). Mean (Standard Deviation). Unit: Follicles

Measure	r-FSH + r-hLH n = 25	r-FSH n = 33
Value	7.2 (1.1)	7.0 (0.8)

Population analysed: ITT population

Primary outcome: Oocytes Recovery Rate

Time frame: At the end of stimulation (Day 2 up to Day 8). Mean (Standard Deviation). Unit: oocytes per >14 mm follicle

Measure	r-FSH + r-hLH n = 25	r-FSH n = 33
Value	0.56 (0.42)	0.50 (0.41)

Population analysed: ITT population

13 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
r-FSH + r-hLH	0 of 25 (0%)	0 of 25 (0%)	Not reported
r-FSH	0 of 33 (0%)	0 of 33 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publicationM.J. Fernández Ramírez, A. Monzó, T. García-Gimeno, J.M. Rubio, V. Montañana, C. Duque, G. Herrero, A. Romeu. Role of LH administration during the follicullar phase in women with risk of low response in ovarian stimulation with FSH and cetrorelix for IVF, REVISTA IBEROAMERICANA DE FERTILIDAD, Vol. 23- nº 5 - Septiembre-Octubre 2006
Results publication in spanish languageLink provided by the sponsor.

Related trials for Ovarian Stimulation

Active, not recruitingPhase 3
Human Menopausal Gonadotropin Research in Infertility Assessing Cumulative Live Birth With Frozen Embryo Transfer.
Infertility (IVF Patients)
RecruitingPhase 2
Autologous Hair Follicle-Derived Secretome and Platelet-Rich Plasma for Premature Ovarian Insufficiency
Premature Ovarian Insufficiency, POI
Active, not recruitingPhase 1/2
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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

Merck KGaA, Darmstadt, Germany

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing r-FSH, r-hLH and Analogous GnRH antagonist in people with Ovarian Stimulation, run by Merck KGaA, Darmstadt, Germany at 1 site in Spain.

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 4 inclusion and 6 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 28 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 30 Jul 2018). 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?

Number of Oocytes Retrieved (time frame: At the end of stimulation (Day 2 up to Day 8)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01112358, which also lists 1 linked publication.

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 28 Aug 2018.