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Low-dose Gonal-f® in Ovulation Induction (LoGo)

Primary Purpose

Infertility, Monofollicular Development

Status
Terminated
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Gonal-f®
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility focused on measuring Monofollicular Development, Gonal-f®, Recombinant Follicle Stimulating Hormone, Ovarian hyperstimulation syndrome (OHSS)

Eligibility Criteria

18 Years - 37 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects eligible for ovulation induction treatment, where monofollicular development is the desired treatment outcome and the dose schedule outlined in the protocol is deemed appropriate
  • Premenopausal female subjects, aged between 18 and 37 years inclusive
  • Subjects desirous of pregnancy/willing to conceive
  • Subjects who are infertile due to chronic anovulation demonstrated by cycle duration of greater than 35 days.
  • Subjects who have been treated with clomifene citrate therapy, according to standard site practice, and have failed to ovulate and/or conceive
  • Subjects with follicle stimulating hormone (FSH) and prolactin (PRL) serum values within the normal range in the early follicular phase
  • Subjects with an overall total antral follicle count greater than 10 (of follicle size greater than or equal to 2 millimeter [mm] and less than 11 mm) (that is, total between both ovaries)
  • Subjects with at least one patent tube, as documented by recent (within 2 years before treatment assignment) hysterosalpingography (HSG) or hysterosalpingo contrast sonography (HyCoSy)
  • Subjects with normal uterine cavity, as documented by recent (within 2 years before treatment assignment) hysteroscopy, HSG or ultrasound scan
  • Subjects with body mass index (BMI) greater than 20 and less than or equal to 32 kilogram per square meter (kg/m^2) (BMI is equal to body weight [kilogram {kg}] divided by Height * Height [square meter {m^2}])
  • Subjects with negative cervical Papanicolaou (PAP) test conducted according to national guidelines and/or standard site practice
  • Male partners of female subjects with sperm compatible with non-assisted fertilization or availability of donor sperm, as confirmed by the Investigator
  • Subjects who are willing and able to comply with protocol requirements and have provided written, informed consent

Exclusion Criteria:

  • Subjects with history of hypersensitivity to the investigational medicinal product (IMP) (active substance follitropin alpha, FSH, or to any of the excipients of Gonal-f®) or any other drug used in the trial (that is, Ovitrelle)
  • Subjects with ovarian enlargement or ovarian cyst unrelated to Polycystic Ovary Syndrome (PCOS), and of unknown origin on ultrasound
  • Subjects with evidence of diminished ovarian reserve (cycle length less than 26 days; FSH above the upper limit of local serum FSH values, total antral follicle count [AFC] in both ovaries less than 10)
  • Subjects with uterine pathology/abnormalities, which in the opinion of the Investigator could impair pregnancy evolution
  • Subjects who have undergone three or more previous miscarriages
  • Subjects with any previous extrauterine pregnancy
  • Pregnant or lactating female subjects
  • Subjects with abnormal gynecological bleeding of unknown etiology.
  • Subjects with previous history of severe ovarian hyper stimulation syndrome (OHSS) (after clomifene treatment)
  • Subjects who have evidence of current or previous pelvic inflammatory disease before treatment assignment
  • Subjects with tumors of the hypothalamus and pituitary gland
  • Subjects with ovarian, uterine or mammary carcinoma
  • Subjects treated with clomifene citrate or gonadotropins within 1 month of the screening evaluation
  • Subjects with any medical condition which, in the opinion of the Investigator, would prevent an effective response, such as primary ovarian failure, or malformations of the reproductive organs incompatible with pregnancy
  • Subjects with any medical condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug
  • Subjects with any clinically significant systemic disease (for example, insulin-dependent diabetes) or any contraindication to being pregnant and/or carrying a pregnancy to term
  • An active substance abuser
  • Known infection with human immunodeficiency virus (HIV), Hepatitis B or C virus in the trial subject or her male partner
  • Subjects who are currently participating in another clinical trial
  • Subjects who are unable to give written informed consent

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research site
  • Research Site
  • Research Site
  • Research Site
  • Research site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Low Dose Gonal-f® Protocol

Standard Low Dose Gonal-f® Protocol

Arm Description

Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.

Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.

Outcomes

Primary Outcome Measures

Percentage of Cycles With Monofollicular Development
The monofollicular development was defined as the number of cycles with monofollicular development only one Follicle Greater Than or Equal (>= to 17 millimeter (mm) and no other follicles Greater than or equal to 14 mm following up to 4 weeks Gonal-f treatment.

Secondary Outcome Measures

Percentage of Cycles With Bifollicular Development
The bifollicular development was defined as the number of cycles with bifollicular development of only two follicles greater than or equal to 17 millimeter.
Percentage of Cycles With Multifollicular Development
The multifollicular development was defined as the number of cycles with multifollicular development of three or more follicles greater than or equal to 14 millimeter
Percentage of Ovulatory Cycles
Ovulation was defined as a serum progesterone (P4 ) level greater than or equal to 10 nanogram per milliliter (ng/mL) or Clinical Pregnancy. Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy.
Percentage of Cycles Wherein Human Chorionic Gonadotropin (hCG) Was Not Administered
Percentage of Cycles Resulting in Clinical Pregnancy
Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy.
Number of Multiple Pregnancy
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.
Number of Fetuses
Number of Miscarriages After Confirmation of Clinical Pregnancy
Miscarriages were calculated per clinical pregnancy, and clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or confirmed by clinical signs of pregnancy. It excludes ectopic pregnancy.
Number of Subjects With Ovarian Hyper Stimulation Syndrome (OHSS)
OHSS was defined as an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations, classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, hemodynamic and metabolic complications.
Duration of Recombinant Follicle Stimulating Hormone (rFSH) Stimulation
Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH) Administered Per Cycle
Change From Baseline in Anti-Mullerian Hormone (AMH) Levels at Week 4
Testosterone Levels
Sex Hormone Binding Globulin (SHBG) Levels

Full Information

First Posted
June 4, 2013
Last Updated
June 30, 2016
Sponsor
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT01871532
Brief Title
Low-dose Gonal-f® in Ovulation Induction
Acronym
LoGo
Official Title
A Multi-Centre, Two-Arm, Interventional, Phase IV Study to Evaluate Tailoring of Recombinant FSH Treatment in Subjects With Chronic Anovulation Using the Gonal-f® Prefilled Pen in Women Undergoing Ovulation Induction
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Terminated
Why Stopped
Study was terminated because of delays in sourcing replacement Investigational Medicinal Product for the study due to manufacturing delays.
Study Start Date
July 2013 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a prospective, multicenter, open-label, comparative and parallel-group study of ovulation induction evaluating tailoring of Recombinant follicle stimulating hormone (FSH) treatment using the Gonal-f® prefilled pen in World Health Organization (WHO) Type 2 anovulatory subjects who have previously failed to conceive with clomifene treatment.
Detailed Description
Subjects will enter a screening period of up to one month before being randomized at the Baseline Visit, which will occur on Day 1 of the subject's menstrual cycle. Each subject will then receive up to 4 weeks treatment with Gonal-f®. If adequate follicular development (assessed by transvaginal ultrasound) is achieved, the subject will proceed to administration of human chorionic gonadotropin (hCG) within 24-48hrs of last Gonal-f® injection (or according to standard site practice). Following administration of hCG, subjects will attempt to become pregnant via intercourse or intrauterine insemination. The method of conception will be determined by the subject's requirements and standard practice at the clinic site. All subjects will be followed up appropriately until confirmation of biochemical pregnancy (hCG + minimum 14 days) and clinical pregnancy (hCG + minimum 42 days, for subjects with positive biochemical pregnancy test).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Monofollicular Development
Keywords
Monofollicular Development, Gonal-f®, Recombinant Follicle Stimulating Hormone, Ovarian hyperstimulation syndrome (OHSS)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low Dose Gonal-f® Protocol
Arm Type
Experimental
Arm Description
Gonal-f was administered subcutaneously daily at a starting dose of 50 International unit (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, with a final increase of 25 IU, up to maximum dose of 100 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.
Arm Title
Standard Low Dose Gonal-f® Protocol
Arm Type
Active Comparator
Arm Description
Gonal-f was administered subcutaneously daily at a starting dose of 50 International Units (IU) for Week 1, then dose was gradually increased by 12.5 IU for two weeks, up to maximum dose of 125 IU, until Week 4 for subjects with minimal response. After adequate follicular development was achieved, the subject was administration human chorionic gonadotropin (hCG) within 24-48 hours of last Gonal-f injection as per investigator discretion.
Intervention Type
Drug
Intervention Name(s)
Gonal-f®
Other Intervention Name(s)
Recombinant follicle stimulating hormone (r-FSH)
Primary Outcome Measure Information:
Title
Percentage of Cycles With Monofollicular Development
Description
The monofollicular development was defined as the number of cycles with monofollicular development only one Follicle Greater Than or Equal (>= to 17 millimeter (mm) and no other follicles Greater than or equal to 14 mm following up to 4 weeks Gonal-f treatment.
Time Frame
Baseline up to 4 weeks
Secondary Outcome Measure Information:
Title
Percentage of Cycles With Bifollicular Development
Description
The bifollicular development was defined as the number of cycles with bifollicular development of only two follicles greater than or equal to 17 millimeter.
Time Frame
Baseline up to 4 weeks
Title
Percentage of Cycles With Multifollicular Development
Description
The multifollicular development was defined as the number of cycles with multifollicular development of three or more follicles greater than or equal to 14 millimeter
Time Frame
Baseline up to 4 weeks
Title
Percentage of Ovulatory Cycles
Description
Ovulation was defined as a serum progesterone (P4 ) level greater than or equal to 10 nanogram per milliliter (ng/mL) or Clinical Pregnancy. Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy.
Time Frame
Baseline up to 42 days post human chorionic gonadotrophin (hCG) administration
Title
Percentage of Cycles Wherein Human Chorionic Gonadotropin (hCG) Was Not Administered
Time Frame
Baseline up to 4 weeks
Title
Percentage of Cycles Resulting in Clinical Pregnancy
Description
Clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It excludes ectopic pregnancy.
Time Frame
35-42 days post hCG administration
Title
Number of Multiple Pregnancy
Description
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.
Time Frame
35-42 days post hCG administration
Title
Number of Fetuses
Time Frame
35-42 days post hCG administration
Title
Number of Miscarriages After Confirmation of Clinical Pregnancy
Description
Miscarriages were calculated per clinical pregnancy, and clinical pregnancy was defined as pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or confirmed by clinical signs of pregnancy. It excludes ectopic pregnancy.
Time Frame
35-42 days post hCG administration
Title
Number of Subjects With Ovarian Hyper Stimulation Syndrome (OHSS)
Description
OHSS was defined as an exaggerated systemic response to ovarian stimulation characterized by a wide spectrum of clinical and laboratory manifestations, classified as mild, moderate or severe according to the degree of abdominal distention, ovarian enlargement and respiratory, hemodynamic and metabolic complications.
Time Frame
up to 42 days post hCG administration
Title
Duration of Recombinant Follicle Stimulating Hormone (rFSH) Stimulation
Time Frame
Baseline up to 4 weeks
Title
Total Dose of Recombinant Follicle Stimulating Hormone (r-FSH) Administered Per Cycle
Time Frame
Baseline up to 4 weeks
Title
Change From Baseline in Anti-Mullerian Hormone (AMH) Levels at Week 4
Time Frame
Baseline, Week 4
Title
Testosterone Levels
Time Frame
Baseline
Title
Sex Hormone Binding Globulin (SHBG) Levels
Time Frame
Baseline

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
37 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects eligible for ovulation induction treatment, where monofollicular development is the desired treatment outcome and the dose schedule outlined in the protocol is deemed appropriate Premenopausal female subjects, aged between 18 and 37 years inclusive Subjects desirous of pregnancy/willing to conceive Subjects who are infertile due to chronic anovulation demonstrated by cycle duration of greater than 35 days. Subjects who have been treated with clomifene citrate therapy, according to standard site practice, and have failed to ovulate and/or conceive Subjects with follicle stimulating hormone (FSH) and prolactin (PRL) serum values within the normal range in the early follicular phase Subjects with an overall total antral follicle count greater than 10 (of follicle size greater than or equal to 2 millimeter [mm] and less than 11 mm) (that is, total between both ovaries) Subjects with at least one patent tube, as documented by recent (within 2 years before treatment assignment) hysterosalpingography (HSG) or hysterosalpingo contrast sonography (HyCoSy) Subjects with normal uterine cavity, as documented by recent (within 2 years before treatment assignment) hysteroscopy, HSG or ultrasound scan Subjects with body mass index (BMI) greater than 20 and less than or equal to 32 kilogram per square meter (kg/m^2) (BMI is equal to body weight [kilogram {kg}] divided by Height * Height [square meter {m^2}]) Subjects with negative cervical Papanicolaou (PAP) test conducted according to national guidelines and/or standard site practice Male partners of female subjects with sperm compatible with non-assisted fertilization or availability of donor sperm, as confirmed by the Investigator Subjects who are willing and able to comply with protocol requirements and have provided written, informed consent Exclusion Criteria: Subjects with history of hypersensitivity to the investigational medicinal product (IMP) (active substance follitropin alpha, FSH, or to any of the excipients of Gonal-f®) or any other drug used in the trial (that is, Ovitrelle) Subjects with ovarian enlargement or ovarian cyst unrelated to Polycystic Ovary Syndrome (PCOS), and of unknown origin on ultrasound Subjects with evidence of diminished ovarian reserve (cycle length less than 26 days; FSH above the upper limit of local serum FSH values, total antral follicle count [AFC] in both ovaries less than 10) Subjects with uterine pathology/abnormalities, which in the opinion of the Investigator could impair pregnancy evolution Subjects who have undergone three or more previous miscarriages Subjects with any previous extrauterine pregnancy Pregnant or lactating female subjects Subjects with abnormal gynecological bleeding of unknown etiology. Subjects with previous history of severe ovarian hyper stimulation syndrome (OHSS) (after clomifene treatment) Subjects who have evidence of current or previous pelvic inflammatory disease before treatment assignment Subjects with tumors of the hypothalamus and pituitary gland Subjects with ovarian, uterine or mammary carcinoma Subjects treated with clomifene citrate or gonadotropins within 1 month of the screening evaluation Subjects with any medical condition which, in the opinion of the Investigator, would prevent an effective response, such as primary ovarian failure, or malformations of the reproductive organs incompatible with pregnancy Subjects with any medical condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug Subjects with any clinically significant systemic disease (for example, insulin-dependent diabetes) or any contraindication to being pregnant and/or carrying a pregnancy to term An active substance abuser Known infection with human immunodeficiency virus (HIV), Hepatitis B or C virus in the trial subject or her male partner Subjects who are currently participating in another clinical trial Subjects who are unable to give written informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck Serono Limited, UK
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Cork
Country
Ireland
Facility Name
Research Site
City
Dublin
Country
Ireland
Facility Name
Research Site
City
Galway
Country
Ireland
Facility Name
Research Site
City
Cambridge
Country
United Kingdom
Facility Name
Research site
City
Cheshunt
Country
United Kingdom
Facility Name
Research Site
City
Derby
Country
United Kingdom
Facility Name
Research Site
City
Edinburgh
Country
United Kingdom
Facility Name
Research Site
City
Glasgow
Country
United Kingdom
Facility Name
Research site
City
London
Country
United Kingdom
Facility Name
Research Site
City
Nottingham
Country
United Kingdom

12. IPD Sharing Statement

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Low-dose Gonal-f® in Ovulation Induction

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