Dose-finding Study of Novel Erythropoiesis Stimulating Protein (NESP) for the Treatment of Anaemia in Subjects With Solid Tumours Receiving Multicycle Chemotherapy

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety of NESP administered by SC injection in subjects with solid tumours and anaemia receiving multicycle chemotherapy. Subjects in this study enter one of two schedules: Schedule 1 or Schedule 2. Schedule 1 is a sequential dose escalation study which consists of Parts A and B. Part A is the initial treatment phase, where the clinically effective dose (CED) of NESP administered every 3 weeks will be determined after 12 weeks of treatment. Part B is an optional 12-week, open-label, dose-maintenance phase that follows Part A. Schedule 2 is a parallel dose-finding study and also consists of Parts A and B. Part A is the initial treatment phase, where the CED of NESP administered every 4 weeks will be determined after 12 weeks of treatment. Part B is an optional 12-week, open-label, dose-maintenance phase that follows Part A.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Dose-finding Study of Novel Erythropoiesis Stimulating Protein (NESP) Administered by Subcutaneous (SC) Injection for the Treatment of Anaemia in Subjects With Solid Tumours Receiving Multicycle Chemotherapy

Conditions
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Anemia, Solid Tumors

Intervention / Treatment
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* Drug: Placebo
* Drug: Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject with solid tumour(s) Anaemia (hgb less than or equal to 11.0 g/dL Planned to receive cyclic chemotherapy At least 6-month life expectancy Eastern Cooperative Oncology Group (ECOG) status of 0 to 2 Adequate renal and liver function At least 18 years of age Exclusion Criteria: Central nervous system disease Iron deficiency Received more than 2 RBC transfusions within 4 weeks before randomisation or any RBC transfusion within 2 weeks before randomisation Received recombinant human erythropoietin (rHuEPO) therapy within 8 weeks before randomisation History of any seizure disorder Cardiac disease Active infection or inflammatory disease Known positive test for HIV infection Known primary haematologic disorder which could cause anaemia Use of other investigational agent(s)/device(s) Pregnant or breast feeding Known hypersensitivity to any recombinant mammalian derived product

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: NESP - Schedule 1 Part A<br>Part A - 4.5, 6.75, 9.0 or 13.5 mcg/kg Q3W for 12 weeks | Drug: Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)<br>* Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)<br>|
| Experimental: NESP - Schedule 2 Part A<br>NESP 9.0, 12.0, 15.0 or 18.0 mcg/kg Q4W for 12 weeks | Drug: Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)<br>* Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)<br>|
| Placebo Comparator: Placebo - Schedule 1 Part A<br>Placebo Q3W for 12 weeks | Drug: Placebo<br>* Placebo<br>|
| Experimental: NESP - Schedule 1 Part B<br>Open-label NESP at the dose of study drug administered at the end of Part A. Increase dose at week 19 if hgb < 13.0g/dL and/or RBC transfusion in previous 2 weeks. | Drug: Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)<br>* Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)<br>|
| Placebo Comparator: Placebo - Schedule 2 Part A<br>Placebo Q4W for 12 weeks | Drug: Placebo<br>* Placebo<br>|
| Experimental: NESP - Schedule 2 Part B<br>Open-label NESP at the dose of study drug administered at the end of Part A | Drug: Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)<br>* Novel Erythropoiesis Stimulating Protein (NESP) (darbepoetin alfa)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of adverse events and antibody formation to NESP |  | throughout the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and proportion of subjects who receive any RBC transfusion, number of units of RBC transfused, and number of days with at least one RBC transfusion during weeks 1-12, 1-4, 5-8, 9-12, and 5-12, with emphasis on the 5-12 week window |  | during weeks 1-12, 1-4, 5-8, 9-12, and 5-12 | 
| Selected domains of quality of life (QOL) measured by FACT-G and FACT-anaemia scales, BSI depression and BSI anxiety scales, and de novo questions |  | throughout the study | 
| Relationship between these QOL measurements and hgb |  |  | 
| Hgb correction to greater than or equal to 12.0 g/dL in the absence of a red blood cell (RBC) transfusion during the preceding 4 weeks during treatment phase |  | during treatment phase | 
| Number and proportion of subjects, during the treatment phase, who achieve a hemoglobin (hgb) response |  | during the treatment phase | 
| Time to hgb response and hgb correction after the initiation of treatment |  | after the initiation of treatment | 
| Change in hgb measured at the end of the treatment phase compared to baseline |  | baseline to end of the treatment phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia, Solid tumors, Multicycle chemotherapy, NESP