Efficacy and Safety of FG-4592 for Treatment of Anemia in Subjects With Lower Risk MDS

Sponsor

FibroGen (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03303066

Collaborator

AstraZeneca (Industry)

Enrollment

Locations

Arms

56.8

Anticipated Duration (Months)

1.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Primary MDS Classified as Very Low, Low or Intermediate Risk With <5% Blasts	Drug: FG-4592 Drug: Placebo	Phase 2/Phase 3

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 6, 2018

Anticipated Primary Completion Date :

Jan 31, 2023

Anticipated Study Completion Date :

Feb 28, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FG-4592 (Open Label, Double-blind, Three times a week) Fixed starting doses (different doses for lower body weight & higher body weight); dose adjustments to hemoglobin levels are allowed during the study.	Drug: FG-4592 Oral Other Names: Roxadustat AZD9941
Placebo Comparator: Placebo (Double-blind, Three times a week) Fixed starting doses (different doses for lower body weight & higher body weight); dose adjustments to hemoglobin levels are allowed during the study.	Drug: Placebo Oral

Arm

Intervention/Treatment

Experimental: FG-4592 (Open Label, Double-blind, Three times a week)

Fixed starting doses (different doses for lower body weight & higher body weight); dose adjustments to hemoglobin levels are allowed during the study.

Drug: FG-4592

Oral

Other Names:

Roxadustat

AZD9941

Placebo Comparator: Placebo (Double-blind, Three times a week)

Fixed starting doses (different doses for lower body weight & higher body weight); dose adjustments to hemoglobin levels are allowed during the study.

Drug: Placebo

Oral

Outcome Measures

Primary Outcome Measures

Proportion of subjects with a hemoglobin response to FG-4592 without transfusion [26 weeks]
Efficacy of roxadustat (FG-4592) in achieving hemoglobin correction and maintenance and reducing the number of red blood cell packs transfused in 26 weeks in comparison to baseline

Secondary Outcome Measures

Evaluate the incidence of treatment emergent adverse events and tolerability of roxadustat [30 weeks]
Adverse events, serious adverse events, vital signs, electrocardiograms, blood pressure, heart rate, and physical exams
Number (%) of subjects with hemoglobin increase ≥ 1.0 g/dL from baseline [26 weeks]
Efficacy of roxadustat (FG-4592) in achieving hemoglobin correction in 26 weeks in comparison to baseline
Time to first hemoglobin response [26 weeks]
Impact of roxadustat (FG-4592) in achieving hemoglobin correction in 26 weeks in comparison to baseline
Change from baseline in hemoglobin in Week 25 to 27 [2 weeks]
Impact of roxadustat (FG-4592) on hemoglobin correction and maintenance in Week 25 to 27 in comparison to baseline
Proportion of subjects with mean Hb ≥ 10.0 g/dL [30 weeks]
Efficacy of roxadustat (FG-4592) in achieving hemoglobin correction and maintenance in comparison to baseline
Incidence of transfusions over the treatment period [26 weeks]
Impact of roxadustat (FG-4592) in the number of red blood cell packs transfused in 26 weeks in comparison to baseline
Effect of roxadustat on quality of life measured by FACT-An and FACIT-F [30 weeks]
Change in raw score from baseline as measured by FACT-An and FACIT-F

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
ESA-naïve (less than 4 weeks of ESA treatment in total, and not within 30 days of Day

ECOG of 0-2 at screen

Key Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country
1	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui	China
2	Anhui Provincial Hospital	Hefei	Anhui	China
3	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui	China
4	China-Japan Friendship Hospital	Beijing	Beijing	China
5	Peking Union Medical College Hospital	Beijing	Beijing	China
6	Peking University First Hospital	Beijing	Beijing	China
7	Peking University Third Hospital	Beijing	Beijing	China
8	Xiyuan Hospital, CACMS	Beijing	Beijing	China
9	Fujian Medical University Union Hospital	Fuzhou	Fujian	China
10	Lanzhou University Second Hospital	Lanzhou	Gansu	China
11	Guangdong General Hospital	Guangzhou	Guangdong	China
12	Nan Fang Hospital	Guangzhou	Guangdong	China
13	Zhuzhou Central Hospital	Zhuzhou	Guangdong	China
14	Hainan Central Hospital	Haikou	Hainan	China
15	Second hospital of Hebei Medical University	Shijiazhuang	Hebei	China
16	Tumor Hospital of Henan province	Zhengzhou	Henan	China
17	Tongji Hospital, Tongji Medical College of HUST	Wuhan	Hubei	China
18	Union Hospital Affiliated Tongji Medical College Huazhong University of Science and Technolog	Wuhan	Hubei	China
19	The Third Xiangya Hospital of Central South University	Changsha	Hunan	China
20	Jiangsu Province Hospital	Nanjing	Jiangsu	China
21	Zhongda Hospital Southeast University	Nanjing	Jiangsu	China
22	The First Affiliated Hospital Of Soochow University	Suzhou	Jiangsu	China
23	Northern Jiangsu People's Hospital	Yangzhou	Jiangsu	China
24	Affiliated Hospital of Shandong University of Traditional Chinese Medicine	Jinan	Shandong	China
25	Qilu Hospital of Shandong University	Jinan	Shandong	China
26	The Affiliated Hospital of Xuzhou Medical University	Jinan	Shandong	China
27	Huashan Hospital Affiliated to Fudan University	Shanghai	Shanghai	China
28	Shanghai Sixth People's Hospital	Shanghai	Shanghai	China
29	Shanghai Tongji Hospital	Shanghai	Shanghai	China
30	Shaanxi Provincial People's Hospital	Xian	Shanxi	China
31	The First Affiliated Hospital of Xi'an Jiao Tong University Medical College	Xian	Shanxi	China
32	Sichuan Provincial People's Hospital	Chengdu	Sichuan	China
33	West China Hospital, Sichuan University	Chengdu	Sichuan	China
34	Blood disease hospital of Chinese Academy of Medical Sciences	Tianjin	Tianjin	China
35	The Second Hospital of Tianjin Medical University	Tianjin	Tianjin	China
36	Tianjin Medical University General Hospital	Tianjin	Tianjin	China
37	First Affiliated Hospital of Kunming Medical University	Kunming	Yunnan	China
38	The First Affiliated Hospital, Zhejiang University Medical College	Hangzhou	Zhejiang	China