Safety and Efficacy in Premenopausal Women With Heavy Menstrual Bleeding (HMB) Associated With Uterine Fibroids (UF)

A Phase 2b Study to Evaluate the Safety and Efficacy of Elagolix in Premenopausal Women With Heavy Menstrual Bleeding Associated With Uterine Fibroids

This is a Phase 2b randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of elagolix alone and in combination with add-back therapy versus placebo on heavy menstrual bleeding in premenopausal women 18 to 51 years of age with uterine fibroids.

Study Overview

• Status: Completed
• Conditions: Uterine Fibroids; Heavy Uterine Bleeding
• Intervention / Treatment: Other: Elagolix placebo; Drug: E2/NETA placebo; Drug: Elagolix; Drug: 0.5 mg estradiol / 0.1 mg norethindrone acetate; Drug: 1 mg estradiol / 0.5 mg norethindrone acetate

• Study Type: Interventional
• Enrollment (Actual): 571
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 51 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subject is pre-menopausal female 18 to 51 years of age at Screening.
• Subject has diagnosis of uterine fibroids documented by a Pelvic Ultrasound.
• Subject has heavy uterine bleeding associated with uterine fibroids.

Exclusion Criteria:

• Subject has had a myomectomy, uterine artery embolization or high intensity focused ultrasound for fibroid destruction within 6 months prior to Screening or endometrial ablation within 5 years prior to Screening.
• Subject has a history of osteoporosis or other metabolic bone disease.
• Subject shows evidence of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric (including depression, schizophrenia, bipolar disorder), or neurologic diseases or any uncontrolled medical illness such as uncontrolled type 2 diabetes. Subject has any history of attempted suicide.
• Subject has a history of clinically significant condition(s) including but not limited to: * Symptomatic Endometriosis * Epilepsy or seizures * Type 1 diabetes * Chronic kidney disease * Any cancer (except treated basal cell carcinoma of the skin), including breast or ovarian cancer or subject has taken any systemic cancer chemotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Cohort 1: Placebo; Placebo for elagolix and placebo for E2/NETA twice daily (BID)	Other: Elagolix placebo; oral coated tablet; Drug: E2/NETA placebo; oral hard capsule
EXPERIMENTAL: Cohort 1: Elagolix 300 mg BID; Elagolix 300 mg BID alone	Drug: E2/NETA placebo; oral hard capsule; Drug: Elagolix; oral coated tablet; Other Names: ABT-620
EXPERIMENTAL: Cohort 1: Elagolix 300 mg BID plus LD E2/NETA QD; Elagolix 300 mg BID plus low-dose (LD) E2/NETA once daily (QD)	Drug: Elagolix; oral coated tablet; Other Names: ABT-620; Drug: 0.5 mg estradiol / 0.1 mg norethindrone acetate; oral hard capsule; Other Names: Activelle, Activella, low dose (LD) E2/NETA
EXPERIMENTAL: Cohort 1: Elagolix 300 mg BID plus SD E2/NETA QD; Elagolix 300 mg BID plus standard-dose (SD) E2/NETA QD	Drug: Elagolix; oral coated tablet; Other Names: ABT-620; Drug: 1 mg estradiol / 0.5 mg norethindrone acetate; oral hard capsule; Other Names: Activella; Activelle; standard dose (SD) E2/NETA
PLACEBO_COMPARATOR: Cohort 2: Placebo; Placebo for elagolix and E2/NETA QD	Other: Elagolix placebo; oral coated tablet; Drug: E2/NETA placebo; oral hard capsule
EXPERIMENTAL: Cohort 2: Elagolix 600 mg QD; Elagolix 600 mg QD alone	Drug: E2/NETA placebo; oral hard capsule; Drug: Elagolix; oral coated tablet; Other Names: ABT-620
EXPERIMENTAL: Cohort 2: Elagolix 600 mg QD plus LD E2/NETA QD; Elagolix 600 mg QD plus LD E2/NETA QD	Drug: Elagolix; oral coated tablet; Other Names: ABT-620; Drug: 0.5 mg estradiol / 0.1 mg norethindrone acetate; oral hard capsule; Other Names: Activelle, Activella, low dose (LD) E2/NETA
EXPERIMENTAL: Cohort 2: Elagolix 600 mg QD plus SD E2/NETA QD; Elagolix 600 mg QD plus SD E2/NETA QD	Drug: Elagolix; oral coated tablet; Other Names: ABT-620; Drug: 1 mg estradiol / 0.5 mg norethindrone acetate; oral hard capsule; Other Names: Activella; Activelle; standard dose (SD) E2/NETA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Menstrual Blood Loss (MBL) Volume of < 80 mL at the Final Month and a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month	The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL Volume of < 80 mL at the Final Month and a ≥50% Reduction in MBL Volume from Baseline to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.	Baseline, Final Month (last 28 days of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 56 to 29 Days of Treatment	The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 56 to 29 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period.	Baseline, second last 28 days of treatment (last 56 to 29 days of treatment)
Percentage of Participants With a MBL Volume < 80 mL and a ≥ 50% Reduction in MBL Volume From Baseline During the Last 84 to 57 Days of Treatment	The percentage of participants meeting a composite endpoint consisting of these 2 bleeding assessments: a MBL volume < 80 mL and a ≥ 50% reduction in MBL volume from baseline during the last 84 to 57 days of last treatment. Baseline is defined as the last qualified menstrual cycle during the screening period.	Baseline, third last 28 days of treatment (last 84 to 57 days of treatment)
Percentage of Participants Who Achieved an MBL Volume of < 80 mL at the Final Month	Percentage of participants who achieved an MBL volume of < 80 mL at the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.	Final Month (last 28 days of treatment)
Percentage of Participants With a ≥ 50% Reduction in MBL Volume From Baseline to the Final Month	Percentage of participants with a >= 50% reduction from baseline in MBL to the Final Month (last 28 days of treatment). Baseline is defined as the last qualified menstrual cycle during the screening period.	Baseline, Final Month (last 28 days of treatment)
Percentage of Participants Who Achieved Amenorrhea During the Last 56 Days of Treatment	Amenorrhea is defined as having 0 days of bleeding or spotting based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding or spotting, based on imputed electronic diary data during the last 56 days of treatment. Participants needed to have at least 66 days on treatment.	Last 56 days of treatment (after 10 days from first dose date)
Percentage of Participants Who Achieved Suppression of Bleeding During the Last 56 Days of Treatment	Suppression of bleeding is defined as having 0 days of bleeding based on observed validated and nonvalidated alkaline hematin data and having 0 days of bleeding (spotting is allowed) based on imputed electronic diary data during the last 56 days of treatment.	Last 56 days of treatment (after 10 days from first dose date)
Mean Change in the Number of Bleeding Days From Baseline to Month 6	The number of days with any bleeding including spotting was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug.	Baseline, Month 6
Mean Change in the Number of Heavy Bleeding Days From Baseline to Month 6	The number of days with heavy bleeding (either heavy or very heavy/gushing bleeding) was calculated using data collected on daily bleeding diary. Baseline is defined as the last 28 days prior to the first dose day of study drug.	Baseline, Month 6
Change in Bleeding Severity Scores From Baseline at the Final Month	The average bleeding score was calculated for each 28-day interval starting on Day 29 using data collected on daily bleeding diary using the Mansfield-Voda-Jorgenson (MVJ) Menstrual Bleeding Scale (1=spotting, 2 = very light bleeding, 3 = light bleeding, 4 = moderate bleeding, 5 = heavy bleeding, 6 = very heavy/gushing bleeding). Baseline is defined as the last 28 days prior to the first day of study drug.	Baseline, Final Month (last 28 days of treatment)
Mean Change in Hemoglobin Concentration From Baseline to Final Visit	Baseline is defined as the last measurement prior to the first dose of study drug.	Baseline, Final Visit during treatment period (Month 6 or early termination)
Mean Percentage Change From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit	Volume of the total fibroid volume (3 largest fibroids), as measured by transvaginal ultrasound, or transabdominal ultrasound.	Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Mean Percentage Change From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit	Volume of the largest fibroid (primary fibroid), as measured by transvaginal ultrasound, or transabdominal ultrasound.	Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Mean Percentage Change From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit	Uterine volume, as measured by transvaginal ultrasound or transabdominal ultrasound.	Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Percentage of Participants With ≥ 25% Reduction From Baseline in Total Fibroid Volume at Month 3, Month 6, and Final Visit	Total fibroid volume (3 largest fibroids) was measured by transvaginal ultrasound, or transabdominal ultrasound.	Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Percentage of Participants With ≥ 25% Reduction From Baseline in Primary Fibroid Volume at Month 3, Month 6, and Final Visit	Volume of the largest fibroid (primary fibroid) was measured by transvaginal ultrasound or transabdominal ultrasound.	Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Percentage of Participants With ≥ 25% Reduction From Baseline in Uterine Volume at Month 3, Month 6, and Final Visit	Uterine volume was measured by transvaginal ultrasound or transabdominal ultrasound.	Baseline, Month 3, Month 6, and Final Visit during treatment period (Month 6 or early termination)
Change From Baseline to Each Month in Non-Bleeding Uterine Fibroids Symptom (NBUFSQ) Questionnaire	The NBUFSQ (8 items) is a brief patient-reported daily diary that assesses non-bleeding symptoms experienced by women with uterine fibroids. It includes 6 items, asking women to rate their symptoms (abdominal/pelvic pain, pressure, and cramping, back pain, bloating, and urinary problems) in the past 24 hours using an 11-point numeric response scale that ranges from 0 (i.e., no symptom) to 10 (i.e., worst possible symptom) and 2 items to address urinary frequency during the daytime and at night. Data presented in the sum of scores to the 6 symptom questions, ranging from 0 (no symptoms) to 60 (worst possible symptoms). Baseline is defined as the last 28 days prior to the first day of study drug. Final Month is defined as the last 28 days prior to and including the last dose date of study drug.	Baseline, Days 1-28, Days 29-56, Days 57-84, Days 85-112, Days 113-140, Days 141-168, Final Month of treatment, Post-treatment (PT) Days 1-28, PT Days 29-56, PT Days 57-84, PT Days 85-112, PT Days 113-140, PT Days 141-168
Percentage of Participants Who Successfully Avoided Surgical or Invasive Procedures for Uterine Fibroids	The percentage of participants who successfully avoided surgical or invasive procedures for Uterine Fibroids was assessed.	Month 6

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: Charlotte Owens, MD, AbbVie

Publications and helpful links

General Publications

• Carr BR, Stewart EA, Archer DF, Al-Hendy A, Bradley L, Watts NB, Diamond MP, Gao J, Owens CD, Chwalisz K, Duan WR, Soliman AM, Dufek MB, Simon JA. Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial. Obstet Gynecol. 2018 Nov;132(5):1252-1264. doi: 10.1097/AOG.0000000000002933.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 8, 2013
• Primary Completion (ACTUAL): June 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: March 21, 2013
• First Submitted That Met QC Criteria: March 21, 2013
• First Posted (ESTIMATE): March 25, 2013

Study Record Updates

• Last Update Posted (ACTUAL): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 7, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Elagolix; ABT-620; Uterine Fibroids; Menorrhagia; Heavy Uterine Bleeding; Leiomyomata; Elagolix sodium
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Uterine Diseases; Connective Tissue Diseases; Neoplasms, Connective Tissue; Menstruation Disturbances; Neoplasms, Muscle Tissue; Hemorrhage; Leiomyoma; Myofibroma; Menorrhagia; Uterine Hemorrhage; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Norethindrone; Norethindrone Acetate
• Other Study ID Numbers: M12-813; 2013-000082-37 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR