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

NCT03263091 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: FGCL-4592-082
• Study Type: interventional
• Target: 184
• Locations: 16 countries
• Sites: 124

Brief Summary

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.

Conditions

Primary MDS (Very Low, Low or Intermediate IPSS-R With <5% Blasts); Anemia

Keywords

Myelodysplastic Syndromes; Anemia; Hemoglobin (Hb); Low Risk Myelodysplastic Syndrome; Low Risk MDS

Outcome Measures

Primary Outcomes (2)

• OL and OL High-EPO Components: Number of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) ≥8 Weeks (≥56 Consecutive Days) Since First Dose in the First 28 Weeks of Treatment

  The RBC TI was defined as the absence of any intravenous (IV) RBC transfusion (packed cell or whole blood) during any consecutive 56 days during the treatment period. Data presented is for number of participants with RBC TI ≥8 weeks (≥56 consecutive days) since first dose in the first 28 weeks of treatment.

  28 weeks

• DB Component: Number of Participants Who Achieved RBC TI ≥56 Consecutive Days Since First Dose in the First 28 Weeks of Treatment

  RBC TI was defined as the absence of any IV RBC transfusion (packed cell or whole blood) during any consecutive 56 days during the treatment period. Data presented is for number of participants with RBC TI ≥56 consecutive days since first dose in the first 28 weeks of treatment.

  28 weeks

Secondary Outcomes (10)

• OL and OL High-EPO Components: Number of Participants Who Achieved TI ≥50% Reduction From Baseline in Number of Packs of Red Blood Cells (pRBC) Transfusions Over 8 Weeks

  Baseline up to Week 8

• DB Component: Number of Participants Who Achieved TI ≥56 Consecutive Days Since First Dose in 52 Weeks of Treatment

  52 weeks

• DB Component: Number of Participants Who Achieved TI ≥56 Consecutive Days Anytime During the Study

  Baseline up to Week 56

• DB Component: Number of Participants Who Achieved ≥50% Reduction From Baseline in Number of pRBC Transfusions Over 8 Weeks

  Baseline up to Week 8

• DB Component: Cumulative Number of Participant Exposure Weeks (PEW) of TI Over the First 28 Weeks of Treatment

  28 weeks

Study Arms (2)

Roxadustat

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Double-blind: Participants will receive placebo matching to roxadustat for a duration of 52 weeks.

Drug: Placebo

Interventions

Roxadustat DRUG

Oral tablets

Also known as: FG-4592, ASP1517, AZD9941

Roxadustat

Placebo DRUG

Oral tablets

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kyntra Bio: lead
• AstraZeneca: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (124)

Investigational Site

Bakersfield, California, 93309, United States

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Beverly Hills, California, 90212, United States

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Burbank, California, 90212, United States

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Encino, California, 91436, United States

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Laguna Hills, California, 92653, United States

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Los Angeles, California, 90095, United States

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Los Angeles, California, 91326, United States

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Oceanside, California, 92056, United States

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Pasadena, California, 91105, United States

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Santa Maria, California, 93454, United States

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Torrance, California, 90505, United States

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Valencia, California, 91355, United States

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Ventura, California, 93003, United States

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Westlake Village, California, 91361, United States

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Whittier, California, 90603, United States

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Grand Junction, Colorado, 81501, United States

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Pembroke Pines, Florida, 33028, United States

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Weston, Florida, 33331, United States

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Atlanta, Georgia, 30322, United States

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Augusta, Georgia, 30912, United States

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St Louis, Missouri, 63110, United States

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Charlotte, North Carolina, 28204, United States

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Canton, Ohio, 44718, United States

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Cleveland, Ohio, 44111, United States

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Cleveland, Ohio, 44195, United States

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Mayfield Heights, Ohio, 44124, United States

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Philadelphia, Pennsylvania, 19106, United States

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Charleston, South Carolina, 29414, United States

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Houston, Texas, 77030, United States

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Charlottesville, Virginia, 22908, United States

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Darlinghurst, New South Wales, 2010, Australia

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Liverpool, New South Wales, 2170, Australia

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South Brisbane, Queensland, 4101, Australia

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Victoria Park, Saint Albans, 3021, Australia

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Hobart, Tasmania, 7000, Australia

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Wilrijk, Antwerpen, 2610, Belgium

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Brussels, Brussels Capital, 1200, Belgium

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Hasselt, Limburg, 3500, Belgium

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Bruges, West-Vlaanderen, 8000, Belgium

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Brussels, Belgium

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Yvoir, 5530, Belgium

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Vancouver, British Columbia, V6E 1M7, Canada

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London, Ontario, N6A5W9, Canada

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Odense, 5000, Denmark

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Nice, Alpes-Maritimes, 06200, France

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Grenoble, Isère, 38043, France

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Paris, France

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Tours, 37044, France

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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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München, Bavaria, 81675, Germany

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Münster, North Rhine-Westphalia, 48149, Germany

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Dresden, Saxony, 01307, Germany

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Leipzig, Saxony, 04103, Germany

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Düsseldorf, 40225, Germany

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Düsseldorf, 40479, Germany

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Vellore, Tamil Nadu, 632 004, India

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Kolkata, West Bengal, 700014, India

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Kfar Saba, Central District, 4428164, Israel

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Ẕerifin, Central District, 70300, Israel

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Nahariya, Northern District, 22100, Israel

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Haifa, 3436212, Israel

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Ramat Gan, 5265601, Israel

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Tel Aviv, 49372, Israel

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Tel Litwinsky, Israel

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Monza, Lombardy, 20900, Italy

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Meldola, Ravenna, 47014, Italy

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Alessandria, 15121, Italy

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Bologna, 40138, Italy

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Florence, 50134, Italy

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Genova, 16132, Italy

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Lecce, 73100, Italy

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Milan, 20089, Italy

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Reggio Calabria, 89124, Italy

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Rimini, Italy

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Roma, 00133, Italy

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Terni, 5100, Italy

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Torino, Italy

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Varese, 21100, Italy

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Bialystok, 15-732, Poland

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Bydgoszcz, 85-168, Poland

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Krakow, 31-513, Poland

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Piła, 64-920, Poland

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Skorzewo, 60-185, Poland

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Słupsk, 76-200, Poland

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Warsaw, 02-172, Poland

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Kaluga, Russian Federation, 248007, Russia

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Moscow, Russian Federation, 111123, Russia

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Moscow, Russian Federation, 123182, Russia

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Moscow, Russian Federation, 129110, Russia

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Omsk, Russian Federation, 644013, Russia

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Saint Petersburg, Russian Federation, 191024, Russia

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Saint Petersburg, Russian Federation, 197089, Russia

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Saint Petersburg, Russian Federation, 197341, Russia

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Saint Petersburg, 197022, Russia

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Incheon, Incheon Gwang'yeogsi, 21565, South Korea

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Incheon, Incheon Gwangyeogsi, 21565, South Korea

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Hwasun, Jeonranamdo, 58128, South Korea

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Seoul, Seoul Teugbyeolsi, 06351, South Korea

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Seoul, 03080, South Korea

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Sabadell, Barcelona, 08208, Spain

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Barcelona, Catalonia, 08003, Spain

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Pamplona, Navarre, 31008, Spain

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Barcelona, 08035, Spain

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Barcelona, 08041, Spain

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Barcelona, 08908, Spain

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Madrid, 28007, Spain

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Madrid, 28034, Spain

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Madrid, 28050, Spain

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Salamanca, 37007, Spain

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Seville, 41009, Spain

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Seville, 41013, Spain

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Valencia, 46026, Spain

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Ankara, 6500, Turkey (Türkiye)

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Dikimevi, 06590, Turkey (Türkiye)

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Izmir, 35340, Turkey (Türkiye)

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Izmir, 59100, Turkey (Türkiye)

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Kayseri, 38039, Turkey (Türkiye)

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Tekirdağ, 59100, Turkey (Türkiye)

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Yenişehir, 33110, Turkey (Türkiye)

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Boston, Lincolnshire, PE21 9QS, United Kingdom

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Headington, Oxford, OX3 7LE, United Kingdom

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Harrow, HA1 3UJ, United Kingdom

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London, SE5 9RS, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Related Publications (1)

• Henry DH, Glaspy J, Harrup R, Mittelman M, Zhou A, Carraway HE, Bradley C, Saha G, Modelska K, Bartels P, Leong R, Yu KP. Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: Open-label, dose-selection, lead-in stage of a phase 3 study. Am J Hematol. 2022 Feb 1;97(2):174-184. doi: 10.1002/ajh.26397. Epub 2021 Nov 9.

  PMID: 34724251 DERIVED

MeSH Terms

Conditions

Anemia; Myelodysplastic Syndromes

Interventions

roxadustat

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Limitations and Caveats

Study did not meet its primary efficacy endpoint; hence, the study was terminated early.

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: FibroGen, Inc.

082MDSstudy@fibrogen.com

415-978-1441

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2017
• First Posted: August 28, 2017
• Study Start: January 29, 2018
• Primary Completion: March 9, 2023
• Study Completion: June 20, 2023
• Last Updated: August 1, 2024
• Results First Posted: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); PL (7); IT (14); AU (5); ES (13); IN (2); RU (9); GB (5); FR (4); CA (2); TU (7); BE (6); KR (5); US (30); DE (7); IL (7)