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

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

Detailed Description
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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.

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

Conditions
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Anemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: FG-4592
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2 Part: FG-4592<br>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<br>* Oral<br>* Other names: AZD9941;|
| Experimental: Phase 3 Part: FG-4592<br>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<br>* Oral<br>* Other names: AZD9941;|
| Placebo Comparator: Phase 3 Part: Placebo<br>Placebo (matching to FG-4592) administered orally TIW for up to 26 weeks. | Drug: Placebo<br>* Oral<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndromes, Anemia, Hemoglobin (Hb), Low Risk Myelodysplastic Syndrome