Efficacy and Safety of FG-4592 for Treatment of Anemia in Patients With Lower Risk MDS With Low Red Blood Cell Transfusion Burden

• ClinicalTrials.gov Identifier: NCT03263091
• Recruitment Status: Recruiting
• First Posted: August 28, 2017
• Last Update Posted: February 9, 2021
• Sponsor: FibroGen
• Collaborators: AstraZeneca; Astellas Pharma Inc
• Information provided by (Responsible Party): FibroGen

Tracking Information

• First Submitted Date: August 22, 2017
• First Posted Date: August 28, 2017
• Last Update Posted Date: February 9, 2021
• Actual Study Start Date: September 7, 2017
• Estimated Primary Completion Date: January 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 23, 2017)

Efficacy of roxadustat (FG-4592) to achieve transfusion independence ≥ 56 consecutive days [ Time Frame: 28 weeks ]

Efficacy of roxadustat (FG-4592) in achieving hemoglobin correction and maintenance and reducing the number of red blood cell packs transfused in 28 weeks in comparison to baseline

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 25, 2017)

• Evaluate the incidence of treatment emergent adverse events of roxadustat [ Time Frame: 52 weeks ]
  Adverse events, serious adverse events, vital signs, electrocardiograms, blood pressure, heart rate, and physical exams
• Evaluate the impact of roxadustat on RBC transfusion requirements [ Time Frame: 52 weeks ]
  Impact of roxadustat (FG-4592) in achieving hemoglobin correction and maintenance and reducing the number of red blood cell packs transfused throughout the course of the study in comparison to baseline
• Effect of roxadustat on quality of life parameters, as measured by PROMIS and EQ-5D-5L assessment [ Time Frame: 52 weeks ]
  Change in raw score from baseline in Physical Function (PF) and Fatigue score as measured by Patient-Reported Outcome Measurement Information System (PROMIS). And change in raw score from baseline in the EuroQol Quality of Life Five Dimensional Five Level Health Questionnaire (EQ-5D-5L) assessment.
• Evaluate transfusion independence ≥ 56 consecutive days [ Time Frame: 52 weeks ]
  Evaluate transfusion independence by measuring the number of red blood cell packs transfused throughout the course of the study in comparison to baseline

Original Secondary Outcome Measures (submitted: August 23, 2017)

• Evaluate the safety of roxadustat [ Time Frame: 52 weeks ]
  Adverse events, serious adverse events, vital signs, electrocardiograms, blood pressure, heart rate, and physical exams
• Evaluate the impact of roxadustat on RBC transfusion requirements [ Time Frame: 52 weeks ]
  Impact of roxadustat (FG-4592) in achieving hemoglobin correction and maintenance and reducing the number of red blood cell packs transfused throughout the course of the study in comparison to baseline
• Effect of roxadustat on quality of life parameters, as measured by PROMIS and EQ-5D-5L assessment [ Time Frame: 52 weeks ]
  Mean change from baseline in Physical Function (PF) and Fatigue score as measured by Patient-Reported Outcome Measurement Information System (PROMIS). And mean change from baseline in the EuroQol Quality of Life Five Dimensional Five Level Health Questionnaire (EQ-5D-5L) assessment.
• Evaluate transfusion independence ≥ 56 consecutive days [ Time Frame: 52 weeks ]
  Evaluate transfusion independence by measuring the number of red blood cell packs transfused throughout the course of the study in comparison to baseline

Current Other Pre-specified Outcome Measures (submitted: August 23, 2017)

Duration of transfusion independence [ Time Frame: 52 weeks ]

Evaluate transfusion independence by measuring the number of red blood cell packs transfused throughout the course of the study in comparison to baseline

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Efficacy and Safety of FG-4592 for Treatment of Anemia in Patients With Lower Risk MDS With Low Red Blood Cell Transfusion Burden
• Official Title: A Phase 3 Randomized Double-Blind Placebo-Controlled Study Investigating the Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Patients With Lower Risk Myelodysplastic Syndrome (MDS) With Low Red Blood Cell (RBC) Transfusion Burden (LTB)
• Brief Summary: The purpose of this study is to determine whether FG-4592 is safe and effective in the treatment of anemia in patients with Lower Risk Myelodysplastic Syndrome and Low Red Blood Cell Transfusion Burden.
• Detailed Description: This study includes an Open-Label Lead in, a Double-Blind component and an Open-Label High Erythropoietin component. In each, there is an up to 42 days screen period followed by a treatment period of 52 weeks and a 4 week end of treatment assessment.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Primary MDS (Very Low, Low or Intermediate IPSS-R With <5% Blasts)

Intervention

• Drug: FG-4592
  Oral
  Other Names:

  • Roxadustat
  • ASP1517
  • AZD9941
• Drug: Placebo
  Oral

Study Arms

• Experimental: FG-4592 (Open Label, Double-blind, Three times a week)
  Weight-based starting doses; dose adjustments to hemoglobin levels are allowed during the study.
  Intervention: Drug: FG-4592
• Placebo Comparator: Placebo (Double-blind, Three times a week)
  Weight-based starting doses; dose adjustments to hemoglobin levels are allowed during the study.
  Intervention: Drug: Placebo
• Experimental: Open-Label High Erythropoietin
  Weight-based starting doses; dose adjustments to hemoglobin levels are allowed during the study.
  Intervention: Drug: FG-4592

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 4, 2021): 204
• Original Estimated Enrollment (submitted: August 23, 2017): 184
• Estimated Study Completion Date: July 2022
• Estimated Primary Completion Date: January 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Diagnosis of primary MDS classified as very low, low or intermediate risk with <5% blasts. There is no minimum time from diagnosis except to allow for proper IPSS-R classification to be made, and to show transfusion dependence.
• RBC transfusion of either 2-4 pRBC units over the 8 weeks prior to randomization or 1 pRBC in two consecutive periods of 8 weeks within the 16 weeks prior to randomization
• No restriction on prior use of ESAs, except no ESA use within 8 weeks prior to registration/randomization
• Pre-transfusion hemoglobin of <= 10 g/dL,
• ECOG of 0-2 at screen
• History of cured malignancy with no evidence of recurrence for a least 3 years are eligible

Key Exclusion Criteria:

• Diagnosis of secondary MDS
• Significant myelofibrosis (>2+fibrosis)
• MDS associated with 5q(del) abnormality
• Screen serum erythropoietin level > 400 mIU/mL (Double Blind); for Open- Label High Erythropoietin patients serum erythropoietin level must be >400 mIU/mL
• Clinically significant anemia due to non-MDS etiologies

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Charles Bradley, PhD; 1-415-978-1672; 082MDSstudy@fibrogen.com

Contact: Katharina Modelska, MD,PhD; 415-978-1803; 082MDSstudy@fibrogen.com

• Listed Location Countries: Germany, Australia, Belgium, Israel, Italy, Korea, Republic of, Russian Federation, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03263091
• Other Study ID Numbers: FGCL-4592-082
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: FibroGen
• Study Sponsor: FibroGen

Collaborators

• AstraZeneca
• Astellas Pharma Inc

• Investigators: Not Provided
• PRS Account: FibroGen
• Verification Date: February 2021