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A Study to Assess the Efficacy and Safety of OBE2109 in Subjects With Endometriosis (EDELWEISS)

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.
 
ClinicalTrials.gov Identifier: NCT02778399
Recruitment Status : Completed
First Posted : May 19, 2016
Results First Posted : July 21, 2022
Last Update Posted : July 21, 2022
Sponsor:
Information provided by (Responsible Party):
ObsEva SA

Brief Summary:
The primary objective of this study is to assess the efficacy and safety of a range of oral doses of OBE2109 versus placebo, in reducing endometriosis associated pain.

Condition or disease Intervention/treatment Phase
Endometriosis Drug: Placebo Drug: OBE2109 Phase 2

Detailed Description:

The study is a prospective, dose-finding, randomized, parallel group, double-blind, placebo-controlled phase 2b study investigating the efficacy and safety of OBE2109 in the treatment of 330 women with moderate-to-severe endometriosis associated pain.

Subject will be randomized to one of 6 treatment groups in a 1:1:1:1:1:1 ratio (1 placebo group, 5 dose groups with different dosage/regimen).

Eligible subjects will be offered the opportunity to continue treatment with OBE2109 in an extension phase. Subjects who do not continue in the extension will enter the treatment-free follow-up phase of the study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 328 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Phase 2b Dose-ranging Study to Assess the Efficacy and Safety of OBE2109 in Subjects With Endometriosis Associated Pain
Actual Study Start Date : July 2016
Actual Primary Completion Date : April 2018
Actual Study Completion Date : July 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: OBE2109 50 mg Drug: OBE2109
OBE2109 tablets for oral administration once daily

Experimental: OBE2109 75mg fixed dose (FD) Drug: OBE2109
OBE2109 tablets for oral administration once daily

Experimental: OBE2109 75mg titrated dose (TD) Drug: OBE2109
OBE2109 tablets for oral administration once daily

Experimental: OBE2109 100mg Drug: OBE2109
OBE2109 tablets for oral administration once daily

Experimental: OBE2109 200 mg Drug: OBE2109
OBE2109 tablets for oral administration once daily

Placebo Comparator: Placebo / OBE2109 100mg
Participants received placebo for the first 12 weeks and were then crossed-over to active treatment with OBE2109 100mg for a further 12 weeks.
Drug: Placebo
Placebo tablets for oral administration once daily

Drug: OBE2109
OBE2109 tablets for oral administration once daily




Primary Outcome Measures :
  1. Percentage of Subjects With 30% or Greater Reduction From Baseline to Week 12 in Mean Overall Pelvic Pain Score (0-3 VRS) [ Time Frame: From baseline to week 12 ]

    The primary efficacy endpoint of the study was a response at Week 12, with response defined as a reduction of 30% or greater from baseline in the mean overall pelvic pain score, defined as the mean of daily pain scores reported in electronic diary during the preceding 28 days (4-week period), assessed on a Verbal Rating Scale for pelvic pain of 0 (no pain) to 3 (severe pain). The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.

    The relevant time points are Baseline and Week 12.



Secondary Outcome Measures :
  1. Change From Baseline to Week 12 in the Mean Overall Pelvic Pain Score (0-10 NRS) [ Time Frame: From baseline to week 12 ]

    This endpoint corresponds to the change from baseline to Week 12 in the mean overall pelvic pain score, defined as the mean of daily pain scores reported in electronic diary during the preceding 28 days (4-week period), assessed on a Numerical Rating Scale (NRS) for pelvic pain of 0 (no pelvic pain) to 10 (worst pelvic pain imaginable). The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.

    The relevant time points are Baseline and Week 12.


  2. Percentage of Subjects With 30% or Greater Reduction From Baseline to Week 12 in Mean Pelvic Pain Scores (0-3 VRS) for Days With Uterine Bleeding [ Time Frame: From baseline to week 12 ]

    This endpoint corresponds to a response at Week 12, with response defined as a reduction of 30% or greater from baseline in the mean pelvic pain score for days with uterine bleeding/spotting, defined as the mean of daily pain scores on days with uterine bleeding/spotting recorded in electronic diary during the preceding 28 days (4-week period), assessed on a Verbal Rating Scale for pelvic pain of 0 (no pain) to 3 (severe pain). The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.

    The relevant time points are Baseline and Week 12.


  3. Percentage of Subjects With 30% or Greater Reduction From Baseline to Week 12 in Mean Pelvic Pain Scores (0-3 VRS) for Days With no Uterine Bleeding [ Time Frame: From baseline to week 12 ]

    This endpoint corresponds to a response at Week 12, with response defined as a reduction of 30% or greater from baseline in the mean pelvic pain score for days with no uterine bleeding, defined as the mean of daily pain scores on days with no uterine bleeding recorded in electronic diary during the preceding 28 days (4-week period) on a Verbal Rating Scale for pelvic pain of 0 (no pain) to 3 (severe pain). The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.

    The relevant time points are Baseline and Week 12.


  4. Change From Baseline to Week 12 in the Mean Dyspareunia Score (0-3 VRS) [ Time Frame: From baseline to week 12 ]

    This endpoint corresponds to the change from baseline to Week 12 in the mean dyspareunia score, defined as the mean of daily dyspareunia scores recorded in electronic diary during the preceding 28 days (4-week period), assessed on a 0-3 Verbal Rating Scale (VRS) for dyspareunia, with 0 representing "No discomfort during sexual intercourse" and 3 representing "I avoided sexual intercourse because of pain". The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.

    The dyspareunia questionnaire also included an option "not applicable: I was not sexually active for reasons other than my endometriosis or did not have sexual intercourse"; for scoring, answering "not applicable" was considered like a missing value.

    The relevant time points are Baseline and Week 12.


  5. Change From Baseline to Week 12 in the Mean Dyschezia Score (0-10 NRS) [ Time Frame: From baseline to week 12 ]

    This endpoint corresponds to the change from baseline to week 12 in the mean dyschezia score, defined as the mean of weekly dyschezia scores reported in electronic diary during the preceding 28 days (4-week period), assessed on a 0-10 Numerical Rating Scale for dyschezia, with 0 representing no pain and 10 representing the worst pain imaginable. The baseline mean score was calculated as the mean of weekly scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.

    The relevant time points are Baseline and Week 12.


  6. Percentage of Subjects With Any Analgesics Use at Week 12 [ Time Frame: Up to week 12 ]
    This endpoint corresponds to the percentage of subjects at week 12 who recorded at least one pain medication intake in electronic diary during the preceding 28 days (4-week period).

  7. Change From Baseline to Week 12 in the Mean Score of Endometriosis Health Profile-30 (EHP-30) Pain Domain [ Time Frame: From baseline to week 12 ]

    This endpoint corresponds to the change from baseline to Week 12 in the mean score of pain dimension of the EHP-30. The EHP-30 questionnaire was answered on electronic diary after activation by site staff during subject's monthly visits at site.

    The EHP-30 pain dimension consists of 11 items each addressing the effect of pain on various activities in the past 4 weeks and each assessed on a 5-point scale (0=Never through to 4=Always). Scaled score was equalled to total of raw score of each item in scale divided by the maximum possible raw score of all the items in the dimension, multiplied by 100, resulting in a score on a scale from 0 (best possible health status) to 100 (worst possible health status).

    The relevant time points are Baseline and Week 12.


  8. Percentage of Subjects With Improvement in the Patient Global Impression of Change (PGIC) Score at Week 12 [ Time Frame: Up to week 12 ]

    The PGIC questionnaire consists of one question rated on a seven point scale (1="Very Much Improved" to 7="Very Much Worse"), with which the subject had to qualify her overall status since the start of the study. The PGIC was answered on electronic diary after activation by site staff during Week 12 visit at site.

    This endpoint corresponds to the percentage of subjects with an "improvement" in the PGIC score, which includes all subjects who answered "Very much improved" or "Much improved" or "Minimally improved" at Week 12.


  9. Percentage of Subjects With an Endometriosis Severity Score of "Severe" at Week 12 [ Time Frame: Up to week 12 ]
    Subject was asked monthly on electronic diary to assess their impression of endometriosis severity, considering the preceding 4-weeks, with following possible answers: no symptoms, very mild, mild, moderate, severe. This question was programmed to raise automatically every 4 weeks on the subject electronic diary. Result reported here is the percentage of subjects who answered "severe" at week 12.

  10. Change From Baseline to Week 12 in the Difficulty in Doing Daily Activities Mean Score [ Time Frame: From baseline to week 12 ]

    This endpoint corresponds to the change from baseline to Week 12 in the mean of daily scores for "difficulty in doing daily activities", assessed via electronic diary during the preceding 28 days (4-week period), on a Numerical Rating Scale (NRS) of 0 (no difficulty doing daily activities) to 10 (unable to do daily activities). The baseline mean score was calculated as the mean of daily scores recorded in electronic diary over the two complete menstrual cycles performed during the screening period.

    The relevant time points are Baseline and Week 12.


  11. Percentage Change From Baseline to Week 24 in Bone Mineral Density (BMD) [ Time Frame: From baseline up to week 24 ]
    Change from baseline to Week 24 in BMD assessed by dual-energy X-ray absorptiometry (DXA) scan of LUMBAR SPINE.

  12. Number of Non Benign Endometrial Biopsies at Week 24 [ Time Frame: Week 24 ]

    Any pathological changes in the endometrium at week 24 were assessed from endometrial biopsies. The number of non benign biopsies at Week 24 is presented per treatment arm.

    Note: an isolated case of hyperplasia (without atypia) was observed at week 12 in the 200 mg group in a subject whose screening biopsy results were normal. A follow-up biopsy at week 24 revealed no abnormalities.


  13. Change From Baseline to Week 24 in Endometrial Thickness Measured by Transvaginal Ultrasound (TVUS) [ Time Frame: From baseline up to week 24 ]
    The endometrium thickness was measured by TVUS at screening and at Week 24 visit by the gynaecologist and result was recorded in mm. This endpoint reports the changes from baseline to Week 24 in the endometrial thickness.

  14. Percentage Change From Baseline to Week 24 in the Clinical Laboratory Assessments: LDL [ Time Frame: From baseline up to week 24 ]
    This endpoint reports the change from baseline up to Week 24 in the clinical laboratory assessments: LDL cholesterol.

  15. Percentage Change From Baseline to Week 24 in Clinical Laboratory Assessments: HDL [ Time Frame: From Baseline up to week 24 ]
    This endpoint reports the change from baseline to week 24 in clinical laboratory assessments: HDL cholesterol.

  16. Percentage Change From Baseline to Week 24 in Clinical Laboratory Assessments: Triglycerides [ Time Frame: From baseline up to week 24 ]
    This endpoint reports the change from baseline to week 24 in clinical laboratory assessments: triglycerides.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • The subject must have had her most recent surgical and - if available - histological, diagnosis of pelvic endometriosis up to 10 years before screening.
  • The subject has moderate to severe endometriosis-associated pain during the screening period.
  • The subject has regular menstrual cycles.
  • The subject has a BMI ≥ 18 kg/m2 at the screening visit.

Key Exclusion Criteria:

  • The subject is pregnant or breast feeding or is planning a pregnancy within the duration of the treatment period of the study.
  • The subject had an interventional surgery for endometriosis performed within a period of 60 days before screening.
  • The subject did not respond to prior treatment with gonadotropin releasing hormone (GnRH) agonists or GnRH antagonists for endometriosis.
  • The subject has a history of, or known osteoporosis or other metabolic bone disease.
  • The subject has chronic pelvic pain that is not caused by endometriosis and requires chronic analgesic / therapy, or that would interfere with the assessment of endometriosis related pain.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02778399


Locations
Show Show 86 study locations
Sponsors and Collaborators
ObsEva SA
Investigators
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Study Director: ObsEva SA Geneva
  Study Documents (Full-Text)

Documents provided by ObsEva SA:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: ObsEva SA
ClinicalTrials.gov Identifier: NCT02778399    
Other Study ID Numbers: 15-OBE2109-001
First Posted: May 19, 2016    Key Record Dates
Results First Posted: July 21, 2022
Last Update Posted: July 21, 2022
Last Verified: June 2022
Keywords provided by ObsEva SA:
Pelvic Pain
Endometriosis
Dysmenorrhea
Dyspareunia
Additional relevant MeSH terms:
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Endometriosis
OBE2109
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs