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Phase III Study Comparing Efficacy and Safety of AFOLIA vs Gonal-f® RFF in Women (35 to 42) Undergoing IVF

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01687712
First Posted: September 19, 2012
Last Update Posted: October 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Fertility Biotech AG
Results First Submitted: September 20, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Infertility
Interventions: Drug: AFOLIA
Drug: Gonal-f® RFF

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
1548 subjects were enrolled, 1101 subjects were randomized and 1100 received Investigational Medicinal Product (IMP) at 22 investigational sites in the United States.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
After the informed consent was signed, each subject received a subject identification number and underwent the down-regulation procedure. After a successful downregulation, subjects were centrally randomized in a 1:1 ratio to one of the treatment groups, AFOLIA or Gonal-f®RFF.

Reporting Groups
  Description
AFOLIA One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Gonal-f® RFF One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.

Participant Flow for 3 periods

Period 1:   Cycle 1
    AFOLIA   Gonal-f® RFF
STARTED   549   551 
Received hCG   516   520 
Oocyte/Ovum Pick Up   513   517 
Fertilization Performed   508   512 
Embryo Transfer   466   483 
Biochemical Pregnancy   163   203 
Clinical Pregnancy [1]   114   138 
COMPLETED [2]   101   122 
NOT COMPLETED   448   429 
Not Biochemically Pregnant                386                348 
Early Pregnancy Loss                43                60 
Ectopic Pregnancy                5                5 
Heterotropic Pregnancy                1                0 
Miscarriage/Spontaneous Abortion                9                14 
Abortion                3                0 
Intrauterine Fetal Death                0                1 
Lost to Follow-up                1                1 
[1] Ascertained via an ultrasound scan.
[2] A subject is listed as Completed if they delivered at least one live neonate.

Period 2:   Cycle 2
    AFOLIA   Gonal-f® RFF
STARTED   109   120 
Received hCG   107   119 
Oocyte/Ovum Pick Up   107   119 
Fertilization Performed   106   119 
Embryo Transfer   101   117 
Biochemical Pregnancy   35   43 
Clinical Pregnancy [1]   17   26 
COMPLETED [2]   16   25 
NOT COMPLETED   93   95 
Not Biochemically Pregnant                74                77 
Early Pregnancy Loss                18                16 
Ectopic Pregnancy                0                1 
Still Birth                1                0 
Miscarriage/Spontaneous Abortion                0                1 
[1] Ascertained via an ultrasound scan.
[2] A subject is listed as Completed if they delivered at least one live neonate.

Period 3:   Cycle 3
    AFOLIA   Gonal-f® RFF
STARTED   28   24 
Received hCG   27   24 
Ooctye/Ovum Pick-Up   27   24 
Fertilization Performed   27   24 
Embryo Transfer   26   24 
Biochemically Pregnant   7   2 
Clinical Pregnancy [1]   5   0 
COMPLETED [2]   4   0 
NOT COMPLETED   24   24 
Not Biochemically Pregnant                21                22 
Early Pregnancy Loss                1                2 
Ectopic Pregnancy                1                0 
Miscarriage/Spontaneous Abortion                1                0 
[1] Ascertained via an ultrasound scan.
[2] A subject is listed as Completed if they delivered at least one live neonate.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat population, defined as all randomized subjects who received at least one dose of the study treatment, based on their randomization.

Reporting Groups
  Description
AFOLIA One subcutaneous injection of 225IU AFOLIA (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Gonal-f® RFF One subcutaneous injection of 225IU Gonal-f® RFF (follitropin alfa) per day (initial dose) for the first 5 days. From day 6 dose could be adjusted up (to a max of 450IU per day) or down (to a min of 75IU per day) in multiple increments of 37.5IU.
Total Total of all reporting groups

Baseline Measures
   AFOLIA   Gonal-f® RFF   Total 
Overall Participants Analyzed 
[Units: Participants]
 549   551   1100 
Age 
[Units: Years]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 549   551   1100 
   37.7  (2.16)   37.8  (2.18)   37.8  (2.17) 
Age, Customized 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 549   551   1100 
35-37      275  50.1%      276  50.1%      551  50.1% 
38-40      201  36.6%      194  35.2%      395  35.9% 
41-42      73  13.3%      81  14.7%      154  14.0% 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 549   551   1100 
Female      549 100.0%      551 100.0%      1100 100.0% 
Male      0   0.0%      0   0.0%      0   0.0% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 549   551   1100 
Hispanic or Latino      96  17.5%      78  14.2%      174  15.8% 
Not Hispanic or Latino      452  82.3%      473  85.8%      925  84.1% 
Unknown or Not Reported      1   0.2%      0   0.0%      1   0.1% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 549   551   1100 
American Indian or Alaska Native      3   0.5%      1   0.2%      4   0.4% 
Asian      40   7.3%      48   8.7%      88   8.0% 
Native Hawaiian or Other Pacific Islander      2   0.4%      1   0.2%      3   0.3% 
Black or African American      61  11.1%      57  10.3%      118  10.7% 
White      435  79.2%      440  79.9%      875  79.5% 
More than one race      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      8   1.5%      4   0.7%      12   1.1% 
Height (m) [1] 
[Units: Meters]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 549   550   1099 
   1.643  (0.0660)   1.642  (0.0684)   1.642  (0.0672) 
[1] Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
Weight (kg) [1] 
[Units: Kilograms]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 541   546   1087 
   70.01  (13.803)   71.12  (13.844)   70.57  (13.828) 
[1] Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
BMI (kg/m^2) [1] 
[Units: Kg/m^2]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 541   545   1086 
   25.92  (4.738)   26.38  (4.784)   26.15  (4.765) 
[1] Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
BMI Category (kg/m^2) 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 549   551   1100 
>=18 to <25      279  50.8%      245  44.5%      524  47.6% 
>=25 to <30      150  27.3%      184  33.4%      334  30.4% 
>=30 to <=38      109  19.9%      112  20.3%      221  20.1% 
>38      3   0.5%      4   0.7%      7   0.6% 
Unknown or Not Reported      8   1.5%      6   1.1%      14   1.3% 
Primary Cause of Infertility [1] 
[Units: Participants]
Count of Participants
     
Unexplained Infertility       
Participants Analyzed 
[Units: Participants]
 549   551   1100 
Unexplained Infertility   225   206   431 
Male Factor       
Participants Analyzed 
[Units: Participants]
 549   551   1100 
Male Factor   189   178   367 
Tubal Factor       
Participants Analyzed 
[Units: Participants]
 549   551   1100 
Tubal Factor   138   169   307 
Mild Endometriosis       
Participants Analyzed 
[Units: Participants]
 549   551   1100 
Mild Endometriosis   59   45   104 
Other       
Participants Analyzed 
[Units: Participants]
 549   551   1100 
Other   28   41   69 
[1] Subjects can have more than one factor that causes infertility, therefore percentages may add up to more than 100.
Infertility Duration [1] 
[Units: Years]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 548   550   1098 
   4.1  (4.61)   4.2  (4.54)   4.1  (4.58) 
[1] Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
Number of previous fresh ART cycles [N(%)] [1] 
[Units: Participants]
Count of Participants
     
Participants Analyzed 
[Units: Participants]
 549   551   1100 
    441  80.3%      440  79.9%      881  80.1% 
    81  14.8%      77  14.0%      158  14.4% 
    20   3.6%      30   5.4%      50   4.5% 
≥3      7   1.3%      4   0.7%      11   1.0% 
[1] Number of previous Assisted Reproductive Technology (ART) cycles a subject had prior to starting Cycle 1.
FSH at screening [1] [2] 
[Units: International units (IU)]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 548   550   1098 
   7.98  (4.636)   7.76  (2.433)   7.87  (3.700) 
[1] Measure of Follicle Stimulating Hormone (FSH) at screening.
[2] Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.
LH at screening [1] [2] 
[Units: International units (IU)]
Mean (Standard Deviation)
     
Participants Analyzed 
[Units: Participants]
 377   385   762 
   5.77  (3.36)   5.74  (2.44)   5.76  (2.93) 
[1] Measure of Luteinizing Hormone (LH) at screening.
[2] Number of subjects analysed is less than the number of subjects in the ITT population due to missing data.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Clinical Pregnancy Rate After One Cycle of Treatment - ITT Population   [ Time Frame: Six weeks post embryo transfer ]

2.  Primary:   Clinical Pregnancy Rate After One Cycle of Treatment - PP Population   [ Time Frame: Six weeks post embryo transfer ]

3.  Secondary:   Exposure to r-hFSH Injections: Days of r-hFSH Stimulation - Cycle 1   [ Time Frame: Measured at discretionary visits between Days 9 and 15 after FSH starts ]

4.  Secondary:   Exposure to r-hFSH Injections: Total Dose of r-hFSH (IU) - Cycle 1   [ Time Frame: Measured at discretionary visits between Days 9 and 15 after FSH starts. ]

5.  Secondary:   Exposure to r-hFSH Injections: Daily Dose of r-hFSH (IU) - Cycle 1   [ Time Frame: Measured at discretionary visits between Days 9 and 15 after FSH starts. ]

6.  Secondary:   Number of Oocytes Retrieved - Cycle 1   [ Time Frame: Visit 8, 34-36 hours after hCG administration ]

7.  Secondary:   Local and Systemic Adverse Events: Dermal Response to Injection - Cycle 1   [ Time Frame: Measure recorded in the Patient Diary which is maintained through entire FSH treatment ]

8.  Secondary:   Local and Systemic Adverse Events: Dermal Response to Injection by Severity - Cycle 1   [ Time Frame: Measure recorded in the Patient Diary which is maintained through entire FSH treatment ]

9.  Secondary:   Overall Summary of Adverse Events (AEs) - Cycle 1   [ Time Frame: Measured from the start of r-hFSH treatment to either end of r-hFSH treament +30 days or end of pregnancy if applicable ]

10.  Secondary:   Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 1   [ Time Frame: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10). ]

11.  Secondary:   Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 2   [ Time Frame: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10). ]

12.  Secondary:   Adverse Events of Special Interest: Ovarian Hyperstimulation Syndrome (OHSS) - Cycle 3   [ Time Frame: Measured either 3 days after ooctye pick up (Visit 9) or 18 +/- 1 days after oocyte pick up (Visit 10). ]

13.  Secondary:   Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 1   [ Time Frame: Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer). ]

14.  Secondary:   Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 2   [ Time Frame: Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer). ]

15.  Secondary:   Number of Subjects With Detectable Specific Serum Binding to FSH by Surface Plasmon Resonance - Cycle 3   [ Time Frame: Immunogenicity samples were taken at baseline, Visit 5 (8 days after start of treatment), Visit 9 (5 days after the end of FSH treatment), Visit 10 (18 +/- 1 days after oocyte retrieval), and Visit 11 (42 +/- 1 days after embryo transfer). ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Executive VP of Regulatory Affairs
Organization: Fertility Biotech AG
e-mail: maria.vazquez@fertilitybiotech.com



Responsible Party: Fertility Biotech AG
ClinicalTrials.gov Identifier: NCT01687712     History of Changes
Other Study ID Numbers: FIN3002
First Submitted: September 3, 2012
First Posted: September 19, 2012
Results First Submitted: September 20, 2017
Results First Posted: October 18, 2017
Last Update Posted: October 18, 2017