Efficacy and Safety of Roxadustat for Treatment of Anemia in Participants With Lower Risk Myelodysplastic Syndrome With Low Red Blood Cell Transfusion Burden

February 28, 2024 updated by: FibroGen

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)

The purpose of this study is to determine whether FG-4592 is safe and effective in the treatment of anemia in participants with lower risk MDS and low red blood cell transfusion burden.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

This study includes an Open-Label Lead in, a Double-Blind component, and an Open-Label High Erythropoietin component. There is a screening period of up to 42 days followed by a treatment period of 52 weeks and a 4-week end of treatment assessment.

Study Type

Interventional

Enrollment (Actual)

184

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia, 2010
        • Investigational Site
      • Liverpool, New South Wales, Australia, 2170
        • Investigational Site
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Investigational Site
    • Saint Albans
      • Victoria Park, Saint Albans, Australia, 3021
        • Investigational Site
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Investigational Site
  • Belgium
      • Brussels, Belgium
        • Investigational Site
      • Yvoir, Belgium, 5530
        • Investigational Site
    • Antwerpen
      • Wilrijk, Antwerpen, Belgium, 2610
        • Investigational Site
    • Brussels Capital Region
      • Bruxelles, Brussels Capital Region, Belgium, 1200
        • Investigational Site
    • Limburg
      • Hasselt, Limburg, Belgium, 3500
        • Investigational Site
    • West-Vlaanderen
      • Brugge, West-Vlaanderen, Belgium, 8000
        • Investigational Site
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6E 1M7
        • Investigational Site
    • Ontario
      • London, Ontario, Canada, N6A5W9
        • Investigational Site
  • Denmark
      • Odense, Denmark, 5000
        • Investigational Site
  • France
      • Paris, France
        • Investigational Site
      • Tours, France, 37044
        • Investigational Site
    • Alpes-Maritimes
      • Nice, Alpes-Maritimes, France, 06200
        • Investigational Site
    • Isère
      • Grenoble, Isère, France, 38043
        • Investigational Site
  • Germany
      • Düsseldorf, Germany, 40225
        • Investigational Site
      • Düsseldorf, Germany, 40479
        • Investigational Site
    • Baden-Wurttemberg
      • Freiburg, Baden-Wurttemberg, Germany, 79106
        • Investigational Site
    • Bayern
      • Munchen, Bayern, Germany, 81675
        • Investigational Site
    • Nordrhein-Westfalen
      • Münster, Nordrhein-Westfalen, Germany, 48149
        • Investigational Site
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Investigational Site
      • Leipzig, Sachsen, Germany, 04103
        • Investigational Site
  • India
    • Tamil Nadu
      • Vellore, Tamil Nadu, India, 632 004
        • Investigational Site
    • West Bengal
      • Kolkata, West Bengal, India, 700014
        • Investigational Site
  • Israel
      • Haifa, Israel, 3436212
        • Investigational Site
      • Ramat Gan, Israel, 5265601
        • Investigational Site
      • Tel Aviv, Israel, 49372
        • Investigational Site
      • Tel HaShomer, Israel
        • Investigational Site
    • HaMerkaz
      • Kfar Saba, HaMerkaz, Israel, 4428164
        • Investigational Site
      • Zerifin, HaMerkaz, Israel, 70300
        • Investigational Site
    • HaZafon
      • Nahariya, HaZafon, Israel, 22100
        • Investigational Site
  • Italy
      • Alessandria, Italy, 15121
        • Investigational Site
      • Bologna, Italy, 40138
        • Investigational Site
      • Firenze, Italy, 50134
        • Investigational Site
      • Genova, Italy, 16132
        • Investigational Site
      • Lecce, Italy, 73100
        • Investigational Site
      • Milano, Italy, 20089
        • Investigational Site
      • Reggio Calabria, Italy, 89124
        • Investigational Site
      • Rimini, Italy
        • Investigational Site
      • Roma, Italy, 00133
        • Investigational Site
      • Terni, Italy, 5100
        • Investigational Site
      • Torino, Italy
        • Investigational Site
      • Varese, Italy, 21100
        • Investigational Site
    • Lombardia
      • Monza, Lombardia, Italy, 20900
        • Investigational Site
    • Ravenna
      • Meldola, Ravenna, Italy, 47014
        • Investigational Site
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Investigational Site
    • Incheon Gwang'yeogsi
      • Incheon, Incheon Gwang'yeogsi, Korea, Republic of, 21565
        • Investigational Site
    • Incheon Gwangyeogsi
      • Incheon, Incheon Gwangyeogsi, Korea, Republic of, 21565
        • Investigational Site
    • Jeonranamdo
      • Hwasun, Jeonranamdo, Korea, Republic of, 58128
        • Investigational Site
    • Seoul Teugbyeolsi
      • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 06351
        • Investigational Site
  • Poland
      • Bialystok, Poland, 15-732
        • Investigational Site
      • Bydgoszcz, Poland, 85-168
        • Investigational Site
      • Krakow, Poland, 31-513
        • Investigational Site
      • Pila, Poland, 64-920
        • Investigational Site
      • Skorzewo, Poland, 60-185
        • Investigational Site
      • Slupsk, Poland, 76-200
        • Investigational Site
      • Warszawa, Poland, 02-172
        • Investigational Site
  • Russian Federation
      • Kaluga, Russian Federation, 248007
        • Investigational Site
      • Moscow, Russian Federation, 111123
        • Investigational Site
      • Moscow, Russian Federation, 123182
        • Investigational Site
      • Moscow, Russian Federation, 129110
        • Investigational Site
      • Omsk, Russian Federation, 644013
        • Investigational Site
      • Saint Petersburg, Russian Federation, 191024
        • Investigational Site
      • Saint Petersburg, Russian Federation, 197089
        • Investigational Site
      • Saint Petersburg, Russian Federation, 197341
        • Investigational Site
      • St. Petersburg, Russian Federation, 197022
        • Investigational Site
  • Spain
      • Barcelona, Spain, 08041
        • Investigational Site
      • Barcelona, Spain, 08035
        • Investigational Site
      • Barcelona, Spain, 08908
        • Investigational Site
      • Madrid, Spain, 28034
        • Investigational Site
      • Madrid, Spain, 28050
        • Investigational Site
      • Madrid, Spain, 28007
        • Investigational Site
      • Salamanca, Spain, 37007
        • Investigational Site
      • Sevilla, Spain, 41009
        • Investigational Site
      • Sevilla, Spain, 41013
        • Investigational Site
      • Valencia, Spain, 46026
        • Investigational Site
    • Barcelona
      • Sabadell, Barcelona, Spain, 08208
        • Investigational Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08003
        • Investigational Site
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Investigational Site
  • Turkey
      • Ankara, Turkey, 6500
        • Investigational Site
      • Dikimevi, Turkey, 06590
        • Investigational Site
      • Izmir, Turkey, 35340
        • Investigational Site
      • Izmir, Turkey, 59100
        • Investigational Site
      • Kayseri, Turkey, 38039
        • Investigational Site
      • Tekirdag, Turkey, 59100
        • Investigational Site
      • Yenisehir, Turkey, 33110
        • Investigational Site
  • United Kingdom
      • Harrow, United Kingdom, HA1 3UJ
        • Investigational Site
      • London, United Kingdom, SE5 9RS
        • Investigational Site
      • Manchester, United Kingdom, M20 4BX
        • Investigational Site
    • Lincolnshire
      • Boston, Lincolnshire, United Kingdom, PE21 9QS
        • Investigational Site
    • Oxford
      • Headington, Oxford, United Kingdom, OX3 7LE
        • Investigational Site
  • United States
    • California
      • Bakersfield, California, United States, 93309
        • Investigational Site
      • Beverly Hills, California, United States, 90212
        • Investigational Site
      • Burbank, California, United States, 90212
        • Investigational Site
      • Encino, California, United States, 91436
        • Investigational Site
      • Laguna Hills, California, United States, 92653
        • Investigational Site
      • Los Angeles, California, United States, 91326
        • Investigational Site
      • Los Angeles, California, United States, 90095
        • Investigational Site
      • Oceanside, California, United States, 92056
        • Investigational Site
      • Pasadena, California, United States, 91105
        • Investigational Site
      • Santa Maria, California, United States, 93454
        • Investigational Site
      • Torrance, California, United States, 90505
        • Investigational Site
      • Valencia, California, United States, 91355
        • Investigational Site
      • Ventura, California, United States, 93003
        • Investigational Site
      • Westlake Village, California, United States, 91361
        • Investigational Site
      • Whittier, California, United States, 90603
        • Investigational Site
    • Colorado
      • Grand Junction, Colorado, United States, 81501
        • Investigational Site
    • Florida
      • Pembroke Pines, Florida, United States, 33028
        • Investigational Site
      • Weston, Florida, United States, 33331
        • Investiational Site
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Investgational site
      • Augusta, Georgia, United States, 30912
        • Investigational Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Investigational Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Investigational Site
    • Ohio
      • Canton, Ohio, United States, 44718
        • Investigational Site
      • Cleveland, Ohio, United States, 44111
        • Investigational Site
      • Cleveland, Ohio, United States, 44195
        • Investigational Site
      • Mayfield Heights, Ohio, United States, 44124
        • Investigational Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19106
        • Investigational Site
    • South Carolina
      • Charleston, South Carolina, United States, 29414
        • Investigational Site
    • Texas
      • Houston, Texas, United States, 77030
        • Investigational Site
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Diagnosis of primary MDS classified by the International Prognostic Scoring System - Revised (IPSS-R) as very low, low or intermediate risk with <5% bone marrow blasts. There is no minimum time from diagnosis to registration/randomization except to allow for proper IPSS-R classification to be made (within 16 weeks prior to randomization), and to show transfusion dependence for participants in both portions of the study.
  • RBC transfusion of either 2-4 pRBC units during the 8 weeks prior to registration/randomization or 1 pRBC in two consecutive periods of 8 weeks within the 16 weeks prior to registration/randomization. Open-Label Lead-in participants only, the requirement to demonstrate transfusion dependence can also be met by a Principal Investigator starting this particular participant on pRBC transfusion during the screening period.
  • No restriction on prior use of recombinant erythropoietins or analogues (erythropoiesis-stimulating agents [ESAs]), except no ESA use within 8 weeks prior to Day 1 registration/randomization.
  • Hemoglobin (Hb) ≤10.0 grams/deciliter (g/dL) during screening
  • Eastern Cooperative Oncology Group (ECOG) of 0-2 at screening

Key Exclusion Criteria:

  • Diagnosis of secondary MDS associated with prior chemotherapy, extensive radiation therapy (>25% of bone marrow reserve), and or/other significant chemical or radiation exposure
  • Significant myelofibrosis (>2+ fibrosis)
  • MDS associated with 5q(del) cytogenetic abnormality
  • Screen serum erythropoietin level > 400 milli-international units (mIU)/milliliter (mL) • Clinically significant anemia, as determined by the investigator, due to non-MDS etiologies such as iron deficiency, vitamin B12 or folate deficiency, autoimmune or hereditary hemolysis or anemia or hemorrhage or hereditary anemia such as sickle cell anemia or thalassemia.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Roxadustat

Open-label, lead-in: Participants will receive sequential escalating roxadustat doses (1.5 milligrams/kilograms [mg/kg], 2.0 mg/kg and 2.5 mg/kg), three times a week (TIW) based upon their actual weight at the randomization visit to identify the starting dose for double-blind period.

Double-blind: Participants will receive roxadustat 2.5 mg/kg TIW based upon their body weight for a duration of 52 weeks.

Open-label: Participants with high serum erythropoietin levels (>400 milli-international units [mIU]/milliliter [mL] mIU/mL) will receive roxadustat 2.5 mg/kg TIW based upon their body weight for a duration of 52 weeks.
Drug: Roxadustat
Oral tablets
Other Names:
  • FG-4592
  • ASP1517
  • AZD9941
Placebo Comparator: Placebo
Double-blind: Participants will receive placebo matching to roxadustat for a duration of 52 weeks.
Drug: Placebo
Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage of Participants who Achieve Transfusion Independence (TI) ≥56 Consecutive Days in the First 28 Weeks of Treatment
Time Frame: 28 weeks
28 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of Participants who Achieve TI ≥56 Consecutive Days Anytime During the Study
Time Frame: Weeks 28 and 52
Weeks 28 and 52
Percentage of Participants who Achieve ≥50% Reduction From Baseline in Number of RBC Transfusion Over Any 8 Weeks
Time Frame: Weeks 28 and 52
Weeks 28 and 52
Cumulative Number of Participant-Exposure-Week of TI
Time Frame: Weeks 28 and 52
Weeks 28 and 52
Number of Packs of Red Blood Cells (pRBC) Packs Transfused Compared to Baseline
Time Frame: Weeks 28 and 52
Weeks 28 and 52
Percentage of Participants who Achieved TI for > 20 Weeks (140 Days)
Time Frame: Weeks 28 and 52
Weeks 28 and 52
Mean Change From Baseline in Physical Function as Measured by Patient Reported Outcomes Measurement Information System (PROMIS)
Time Frame: Baseline, Weeks 9, 17, 28, 52 and 56
Baseline, Weeks 9, 17, 28, 52 and 56
Mean Change From Baseline in PROMIS Fatigue Score
Time Frame: Baseline, Weeks 9, 17, 28, 52 and 56
Baseline, Weeks 9, 17, 28, 52 and 56
Mean Change From Baseline in EuroQol Quality of Life Five Dimensional Five Level Health Questionnaire (EQ-5D-5L) Assessment Score
Time Frame: Baseline, Weeks 9, 17, 28, 52 and 56
Baseline, Weeks 9, 17, 28, 52 and 56

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

FibroGen

Collaborators

AstraZeneca
Astellas Pharma Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 7, 2017

Primary Completion (Actual)

March 9, 2023

Study Completion (Actual)

June 22, 2023

Study Registration Dates

First Submitted

August 22, 2017

First Submitted That Met QC Criteria

August 23, 2017

First Posted (Actual)

August 28, 2017

Study Record Updates

Last Update Posted (Estimated)

March 1, 2024

Last Update Submitted That Met QC Criteria

February 28, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FGCL-4592-082

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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