Luteal Hormone Supplementation in In-vitro FertilizationPhase 3NCT01863680

Phase 3 Trial to Evaluate the Efficacy and Safety of COL-1620 Vaginal Progesterone Gel

A Phase 3 study testing COL-1620, Gonadotropin-releasing hormone (GnRH) analogue and Follicle-stimulating hormone (FSH) in people with Luteal Hormone Supplementation in In-vitro Fertilization and Embryo Transfer, run by Merck KGaA, Darmstadt, Germany at 5 sites in Japan.

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

The primary objective of this trial is to demonstrate the non-inferiority of the clinical pregnancy rate per embryo transfer to the historical standard value in in-vitro fertilization (IVF)/embryo transfer (ET) cycles in Japan (Japan Society of Obstetrics and Gynecology [JSOG] 2009 registry data: 24.3 percent [%]). Read more about this study

Who is it for?: Ages 20 to 45 years, women only
Conditions the study is for: Luteal Hormone Supplementation in In-vitro Fertilization, Embryo Transfer
What is being tested?: COL-1620, Gonadotropin-releasing hormone (GnRH) analogue and Follicle-stimulating hormone (FSH)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 178 participants
Where: 5 sitesJapan
Study dates: Jul 2013to Oct 2014
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 20 to 45 years
Women only
No healthy volunteers
Adult

Who may be able to join

Japanese race
Woman with a history of infertility and in whom In-vitro fertilization and embryo transfer (IVF/ET) is indicated
The controlled ovarian stimulation (COS) therapy is gonadotropin-releasing hormone (GnRH) analogue (agonist or antagonist) in combination with a follicle-stimulating hormone (FSH) containing preparation
Healthy premenopausal woman aged between 20 and 45 years (inclusive) and wishing to conceive
Body mass index (BMI) of 17.0 to 25.0 kilogram per square meter (kg/m^2) (inclusive)
A negative pregnancy test (urinary beta-human chorionic gonadotropin [hCG]) prior to starting COS

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Normal cervical smear result (Papanicolaou [PAP] test: Negative for Intraepithelial Lesion or Malignancy [NILM] or [Atypical Squamous Cells of Undetermined Significance {ASC-US} and Human Papillomavirus {HPV} negative]) within 12 months prior to the date of informed consent. If not available, a cervical smear and HPV test will be performed as part of Screening
No clinically significant abnormal findings in the screening hematology, biochemistry and urinalysis parameters
Full comprehension of the study and voluntary written informed consent obtained in writing prior to any trial-related activities

Who cannot join

History of recurrent pregnancy loss (defined as 3 or more previous spontaneous abortions)
History of 3 or more consecutive cancelled or failed (no clinical pregnancy) IVF/ET cycles
Abnormal hemorrhage of the reproductive tract of undetermined origin
Any contraindication to being pregnant and/or carrying a pregnancy to term (for example, malformations of sexual organs or fibroid tumors of the uterus incompatible with pregnancy)
Uterine myoma requiring treatment
Extra-uterine pregnancy within the last 3 months prior to the date of informed consent

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History or presence of intracranial tumor (for example, hypothalamic or pituitary tumor)
Presence of or suspected gonadotropin- or estrogen-dependent malignancy (for example, ovarian, uterine or mammary carcinoma)
Ovarian enlargement or cyst of unknown etiology
Breast-feeding or lactation
History of severe Ovarian Hyperstimulation Syndrome (OHSS) (Classification of OHSS Severity, as per Japan Reproductive/Endocrine Working Group)
Known Human Immunodeficiency Virus (HIV)-positive status, or a history of or current active infection with Hepatitis B or C
Known allergy or hypersensitivity to progesterone preparations or gonadotropin preparations and/or their excipients, or any contraindication to receive medication for controlled ovarian stimulation (for example, gonadotropin, GnRH analogues, combined oral contraceptive pill, as appropriate)
History of or suspected alcohol or substance abuse within 5 years prior to the date of informed consent
Clinically significant systemic disease (for example, insulin-dependent diabetes, epilepsy, severe migraine, acute porphyria, hepatic, renal or cardiovascular disease, severe corticosteroid-dependent asthma)
Active thrombophlebitis, thromboembolic disorder or cerebral apoplexy, or a history of such conditions
Other significant disease that in the Investigator's or Sub-Investigator's opinion would exclude the subject from the trial
Participation in another clinical trial within 3 months prior to the date of informed consent or simultaneous participation in another clinical trial
Legal incapacity or limited legal capacity

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Japan5 sites

Research site
Fujimino
Research site
Kobe
Research site
Osaka
Research site
Sagamihara
Research site
Yokohama, Kanagawa

Other trials in Japan

About this study

Official title: Open-label, Single-arm, Multicenter Phase III Trial to Evaluate the Efficacy and Safety of COL-1620 8% Vaginal Progesterone Gel for Luteal Phase Support in In-vitro Fertilization and Embryo Transfer (IVF/ET) Cycles in Japanese Women

Conditions: Luteal Hormone Supplementation in In-vitro Fertilization, Embryo Transfer
Being tested: COL-1620, Gonadotropin-releasing hormone (GnRH) analogue, Follicle-stimulating hormone (FSH), Human Chorionic Gonadotropin (hCG)
Keywords: Infertility, COL-1620, progesterone gel, Fertilization in Vitro, Embryo Transfer
Medical subject headings: Infertility

What participants receive

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

COL-1620Drug
The subjects will be administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8 percent [%] gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12.
Gonadotropin-releasing hormone (GnRH) analogueDrug
Subjects will undergo conventional controlled ovarian stimulation (COS) therapy for in-vitro Fertilization and Embryo Transfer (IVF/ET) according to the Investigator's discretion using GnRH analogue (agonist or antagonist) preparation.
Follicle-stimulating hormone (FSH)Drug
Subjects will undergo conventional COS therapy for IVF/ET according to the Investigator's discretion using FSH containing preparation.
Human Chorionic Gonadotropin (hCG)Drug
Subjects will undergo conventional COS therapy for IVF/ET according to the Investigator's discretion using hCG preparation.

Study groups in NCT01863680
Study group	Role	What they receive
COL-1620	Experimental	Not described Receives: Drug: COL-1620; Drug: Gonadotropin-releasing hormone (GnRH) analogue; Drug: Follicle-stimulating hormone (FSH); Drug: Human Chorionic Gonadotropin (hCG)

What is being measured

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

Clinical Pregnancy Rate Per Embryo Transfer
Clinical pregnancy was defined as the presence of a fetal sac on transvaginal ultrasound (TVUS) during Week 5 or the presence of an extra-uterine pregnancy (as confirmed during surgery or by 2 positive serum beta-human chorionic gonadotropin (beta-hCG) results from Week 5). The clinical pregnancy rate was calculated as number of subjects who were clinically pregnant divided by the number of subjects who had at least 1 embryo transferred.
Measured: Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])

Secondary outcomes (2)

Biochemical Pregnancy Rate Per Embryo Transfer
Biochemical pregnancy was defined as any miscarriage without any evidence of a fetal sac on TVUS during Visit 6 (Week 5), but with a positive serum beta-hCG pregnancy test result at Visit 5 (Day 14+/-3). Biochemical pregnancy rate was calculated as the number of subjects who had no fetal sac observed during Visit 6 (Week 5) TVUS assessment or subjects who had a positive serum pregnancy test at Visit 5 (Day 14+/-3) and no data recorded at Visit 6 (Week 5) divided by the number of subjects who has at least 1 embryo transferred.
Measured: Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])
Serum Progesterone Level
Two pharmacokinetic (PK) samples were collected per subject for the measurement of serum progesterone concentrations; 1st sample at Visit 2-2 (prior to hCG administration) and second sample during Visit 5 (Day 14+/-3, 7 hours after the morning of investigational medicinal product administration).
Measured: Visit 2-2 (Prior to hCG administration) and Visit 5 (Day 14+/-3)

Timeline

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

Jul 2013Oct 2014

First posted29 May 2013 (estimated)
Study startJul 2013
Primary completionOct 2014
Study completionOct 2014

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 Luteal Hormone Supplementation in In-vitro FertilizationStudies 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: 178 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01863680
Sponsor's protocol ID: EMR200113_001
Status last verified: Nov 2015
First submitted: 23 May 2013
Last updated: 21 Dec 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Study at a glance

From the registry record, last updated by the sponsor on 21 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open-label, Single-arm, Multicenter Phase III Trial to Evaluate the Efficacy and Safety of COL-1620 8% Vaginal Progesterone Gel for Luteal Phase Support in In-vitro Fertilization and Embryo Transfer (IVF/ET) Cycles in Japanese Women
ClinicalTrials.gov ID: NCT01863680
Acronym / sponsor ID: EMR200113_001
Conditions: Luteal Hormone Supplementation in In-vitro Fertilization, Embryo Transfer
Keywords: Infertility, COL-1620, progesterone gel, Fertilization in Vitro, Embryo Transfer
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 178 participants (actual)
Lead sponsor: Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
Study start: Jul 2013
Primary completion: Oct 2014 (actual)
Study completion: Oct 2014 (actual)
First posted: 29 May 2013 (estimated)
Results: Posted 21 Dec 2015

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
COL-1620	Experimental	Drug: COL-1620, Drug: Gonadotropin-releasing hormone (GnRH) analogue, Drug: Follicle-stimulating hormone (FSH), Drug: Human Chorionic Gonadotropin (hCG)

Who may qualify

Ages: 20 to 45 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (9 listed)

Japanese race
Woman with a history of infertility and in whom In-vitro fertilization and embryo transfer (IVF/ET) is indicated
The controlled ovarian stimulation (COS) therapy is gonadotropin-releasing hormone (GnRH) analogue (agonist or antagonist) in combination with a follicle-stimulating hormone (FSH) containing preparation
Healthy premenopausal woman aged between 20 and 45 years (inclusive) and wishing to conceive
Body mass index (BMI) of 17.0 to 25.0 kilogram per square meter (kg/m^2) (inclusive)

Key exclusion criteria (19 listed)

History of recurrent pregnancy loss (defined as 3 or more previous spontaneous abortions)
History of 3 or more consecutive cancelled or failed (no clinical pregnancy) IVF/ET cycles
Abnormal hemorrhage of the reproductive tract of undetermined origin
Any contraindication to being pregnant and/or carrying a pregnancy to term (for example, malformations of sexual organs or fibroid tumors of the uterus incompatible with pregnancy)
Uterine myoma requiring treatment

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
COL-1620The subjects will be administered with COL-1620 vaginal progesterone gel (1.125 grams of progesterone gel containing 90 milligram that is 8 percent [%] gel) vaginally once daily, from the day of ovum pick-up (OPU) until Week 12.	Drug	COL-1620
Gonadotropin-releasing hormone (GnRH) analogueSubjects will undergo conventional controlled ovarian stimulation (COS) therapy for in-vitro Fertilization and Embryo Transfer (IVF/ET) according to the Investigator's discretion using GnRH analogue (agonist or antagonist) preparation.	Drug	COL-1620
Follicle-stimulating hormone (FSH)Subjects will undergo conventional COS therapy for IVF/ET according to the Investigator's discretion using FSH containing preparation.	Drug	COL-1620
Human Chorionic Gonadotropin (hCG)Subjects will undergo conventional COS therapy for IVF/ET according to the Investigator's discretion using hCG preparation.	Drug	COL-1620

Primary outcome

Clinical Pregnancy Rate Per Embryo Transfer
Time frame: Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])
Clinical pregnancy was defined as the presence of a fetal sac on transvaginal ultrasound (TVUS) during Week 5 or the presence of an extra-uterine pregnancy (as confirmed during surgery or by 2 positive serum beta-human chorionic gonadotropin (beta-hCG) results from Week 5). The clinical pregnancy rate was calculated as number of subjects who were clinically pregnant divided by the number of subjects who had at least 1 embryo transferred.

2 secondary outcomes

Biochemical Pregnancy Rate Per Embryo Transfer
Time frame: Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])
Serum Progesterone Level
Time frame: Visit 2-2 (Prior to hCG administration) and Visit 5 (Day 14+/-3)

Results and safety

Results posted to the registry on 21 Dec 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
COL-1620	178	121

Primary outcome: Clinical Pregnancy Rate Per Embryo Transfer

Time frame: Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU]). Number. Unit: Percentage of pregnancy/embryo transfer

Measure	COL-1620 n = 123
Value	28.5

Population analysed: The intention-to-treat subjects included all the subjects who underwent IVF/ET.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of study drug administration up to Week 15. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
COL-1620	5 of 149 (3.4%)	92 of 149 (61.7%)	Not reported

Limitations and caveats (from the sponsor): This study was not a randomized controlled study and did not included an active control arm, however it was designed to allow for comparison with historical IVF-ET data from Japan.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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 Serono Co., Ltd., Japan

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

Questions about this trial

What is this clinical trial studying?

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 9 inclusion and 19 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 21 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Japan. 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 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 21 Dec 2015). 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?

Clinical Pregnancy Rate Per Embryo Transfer (time frame: Week 5 post embryo transfer (2-6 days after Ovum Pick-up [OPU])). 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 NCT01863680.

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 21 Dec 2015.