Efficacy and Safety of FG-4592 for Treatment of Anemia in Participants With Lower Risk Myelodysplastic Syndrome (MDS)

A Phase 2/3 Trial of FG-4592 for Treatment of Anemia in Subjects With Lower Risk Myelodysplastic Syndrome

The objective of this study to evaluate the efficacy FG-4592 for the treatment of anemia in Chinese participants with lower risk MDS.

Study Overview

• Status: Completed
• Conditions: Anemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: FG-4592

Detailed Description

This is a Phase 2/3 trial with sequential Phase 2 and Phase 3 components. In each part, there is an up to 4 weeks screening period followed by a treatment period of 26 weeks and a 4 week follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • The First Affiliated Hospital of Bengbu Medical College
    • Hefei, Anhui, China
      • Anhui Provincial Hospital
    • Hefei, Anhui, China
      • The First Affiliated Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China
      • China-Japan Friendship Hospital
    • Beijing, Beijing, China
      • Peking University Third Hospital
    • Beijing, Beijing, China
      • Peking University First Hospital
    • Beijing, Beijing, China
      • Xiyuan Hospital, CACMS
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
  • Gansu
    • Lanzhou, Gansu, China
      • Lanzhou University Second Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Guangdong General Hospital
    • Guangzhou, Guangdong, China
      • Nan Fang Hospital
    • Zhuzhou, Guangdong, China
      • ZhuZhou Central Hospital
  • Hainan
    • Haikou, Hainan, China
      • Hainan Central Hospital
  • Hebei
    • Shijiazhuang, Hebei, China
      • Second Hospital of Hebei Medical University
  • Henan
    • Zhengzhou, Henan, China
      • Tumor Hospital of Henan province
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital, Tongji Medical College of HUST
    • Wuhan, Hubei, China
      • Union Hospital Affiliated Tongji Medical College Huazhong University of Science and Technolog
  • Hunan
    • Changsha, Hunan, China
      • The Third Xiangya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China
      • Zhongda Hospital Southeast University
    • Suzhou, Jiangsu, China
      • The First Affiliated Hospital of Soochow University
    • Yangzhou, Jiangsu, China
      • Northern Jiangsu People's Hospital
  • Shandong
    • Jinan, Shandong, China
      • Qilu Hospital of Shandong University
    • Jinan, Shandong, China
      • Affiliated Hospital of Shandong University of Traditional Chinese Medicine
    • Jinan, Shandong, China
      • The Affiliated Hospital of Xuzhou Medical University
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Sixth People's Hospital
    • Shanghai, Shanghai, China
      • Huashan Hospital Affiliated to Fudan University
    • Shanghai, Shanghai, China
      • Shanghai Tongji Hospital
  • Shanxi
    • Xian, Shanxi, China
      • Shaanxi Provincial People's Hospital
    • Xian, Shanxi, China
      • The First Affiliated Hospital of Xi'an Jiao Tong University Medical College
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China
      • Sichuan Provincial People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University General Hospital
    • Tianjin, Tianjin, China
      • Blood disease hospital of Chinese Academy of Medical Sciences
    • Tianjin, Tianjin, China
      • The Second Hospital of Tianjin Medical University
  • Yunnan
    • Kunming, Yunnan, China
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital, Zhejiang University Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Diagnosis of primary MDS classified as very low, low or intermediate risk with <5% blasts (documented within 12 weeks prior to Day 1)
• Screening Hb <10 g/dL and ≥6g/dL
• Transfusion independent defined as no red blood cell transfusions within 12 weeks of Day 1
• Erythropoiesis-stimulating agent (ESA)-naïve (not within 30 days of Day 1)
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

Key Exclusion Criteria:

• Diagnosis of secondary MDS
• Significant myelofibrosis (>2+fibrosis)
• Prior therapy with azacitidine, decitabine, antithymocyte globulin, cyclosporine, thalidomide, or lenalidomide within 12 weeks prior to Day 1
• Baseline erythropoietin level of >400 units (U)/liter (L)
• Clinically significant anemia due to non-MDS etiologies

Note: Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2 Part: FG-4592; Fixed starting doses (different doses for lower body weight & higher body weight) of FG-4592 administered orally 3 times a week (TIW) for up to 26 weeks; dose adjustments to Hb levels are allowed during the study.	Drug: FG-4592; Oral; Other Names: AZD9941; Roxadustat
Experimental: Phase 3 Part: FG-4592; Fixed starting doses (different doses for lower body weight & higher body weight) of FG-4592 administered orally TIW for up to 26 weeks; dose adjustments to Hb levels are allowed during the study.	Drug: FG-4592; Oral; Other Names: AZD9941; Roxadustat
Placebo Comparator: Phase 3 Part: Placebo; Placebo (matching to FG-4592) administered orally TIW for up to 26 weeks.	Drug: Placebo; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Hemoglobin (Hb) Response to FG-4592 Without Transfusion	Hemoglobin response to FG-4592 is defined as an increase in mean Hb of ≥1.0 grams (g)/deciliter (dL) from baseline within any 8-week period during the study without transfusion.	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Hb Increase ≥1.0 g/dL From Baseline	Hb response to FG-4592 is defined as an increase in mean Hb of ≥1.0 g/dL from baseline within any 8-week period during the study without transfusion.	26 weeks
Time to First Hb Response	Hb response to FG-4592 is defined as an increase in mean Hb of ≥1.0 g/dL from baseline within any 8-week period during the study without transfusion.	26 weeks
Change From Baseline in Mean Hb in Weeks 25 to 27		Baseline, Weeks 25 to 27
Percentage of Participants With Mean Hb ≥10.0 g/dL Within Any 8-week Period During the Study Without Transfusion		26 weeks
Number of Participants that Require Transfusions or Hb <6 g/dL up to Week 27		Up to Week 27
Mean Change From Baseline in Functional Assessment of Cancer Therapy - Anemia (FACT-An) and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Scores at Week 27	Frame: Baseline, Week 27	30 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to maximum hemoglobin level	Impact of roxadustat (FG-4592) in achieving hemoglobin correction and maintenance in comparison to baseline	30 weeks
Time to maximum hemoglobin increase	Efficacy of roxadustat (FG-4592) in achieving hemoglobin correction in 26 weeks in comparison to baseline	26 weeks
Duration of transfusion independence	Evaluate transfusion independence by measuring the number of red blood cell packs transfused throughout the course of the study in comparison to baseline	30 weeks

Collaborators and Investigators

• Sponsor: FibroGen
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2018
• Primary Completion (Actual): January 11, 2023
• Study Completion (Actual): February 8, 2023

Study Registration Dates

• First Submitted: October 2, 2017
• First Submitted That Met QC Criteria: October 2, 2017
• First Posted (Actual): October 5, 2017

Study Record Updates

• Last Update Posted (Actual): May 3, 2023
• Last Update Submitted That Met QC Criteria: May 1, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Anemia; Myelodysplastic Syndromes; Hemoglobin (Hb); Low Risk Myelodysplastic Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Anemia
• Other Study ID Numbers: FGCL-4592-813

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No