Efficacy of NOX-H94 on Anemia of Chronic Disease in Patients With Cancer

Study Overview
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Brief Summary
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This study is conducted to determine the safety, tolerability, and efficacy of NOX-H94 in patients with anemia of chronic disease (ACD). Furthermore, this study is intended to provide data needed to correlate plasma concentrations of NOX-H94 with its efficacy and to choose the appropriate dose and dose schedule of subsequent efficacy studies. Some chronic diseases, e.g. tumors, inflammation, renal disease, are associated with high hepcidin concentrations in the blood. These hepcidin concentrations cause a reduction in iron concentrations in the blood and subsequently impair formation of red blood cells. Treatment with NOX-H94 is expected to inhibit this patho-mechanism by binding and inactivating hepcidin.

Official Title
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Phase IIa Study to Characterize the Effects of the Spiegelmer® NOX H94 on Anemia of Chronic Disease in Patients With Cancer

Conditions
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Anemia of Chronic Disease

Intervention / Treatment
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* Drug: NOX-H94
* Drug: Placebo solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Female or male aged >18 years Clinically significant anemia of chronic disease (ACD) attributed to histologically or cytologically proven malignancy, either hematological or solid tumor, of any grade or stage: Hemoglobin (Hb) 7.0 g/dL to 10 g/dL, Transferrin saturation (TSAT) <50%, Serum iron <50 µg/dL (SI: <9.0 µmol/L), AND Ferritin >30 ng/mL (SI: >30 µg/L) Previous treatment with systemic anti-cancer therapy / regimen Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 Estimated life expectancy ≥12 weeks Men must agree to follow effective contraception methods during treatment and for 3 months after completion of treatment. Women of childbearing potential must agree to use two forms of effective contraception during treatment and for 3 months after completion of treatment. Exclusion Criteria: Inability to personally provide written informed consent or to understand and collaborate throughout the study History of pure red cell aplasia, thalassemia major or sickle cell disease History of anemia unrelated to cancer <10 g/dL within 6 months prior to screening Uncorrected iron deficiency Regular need for blood transfusions at intervals <6 weeks Acute or myeloid leukemia Known or suspected chronic bleeding Tumor with gastro-intestinal involvement without negative test for fecal occult blood Suspected or known history of hemochromatosis Known infection with human immunodeficiency virus, hepatitis B, or hepatitis C Impaired liver function with bilirubin ≥2.0 mg/dL (26 μmol/L), AST or ALT ≥2 times upper limit History or risk of significant hepatic disease, e.g. chronic alcohol abuse, hepatic steatosis, hepatic cirrhosis, or organ transplantation Severe renal impairment: estimated glomerular filtration rate (eGFR) <30 mL/min (Cockcroft-Gault) Known central nervous system malignancy or metastasis Significant cardiac disease (e.g. uncontrolled hypertension: systolic blood pressure [BP] >150 mmHg or diastolic BP >100 mmHg; myocardial infarction or unstable angina pectoris) within 6 months prior to screening Positive pregnancy test (serum ß-hCG at screening, urine pregnancy test prior to first treatment) or lactation Previous participation in this study or treatment with an investigational agent <21 days prior to treatment start Hemolysis or bleeding >500 mL (measured or estimated) within 6 weeks prior to treatment start Treatment with erythropoiesis-stimulating agents (ESAs) or red blood cell (RBC) transfusions <21 days prior to treatment start Cytotoxic anti-tumor treatment <21 days prior to treatment start or planned during the anticipated study period (within 3 months from treatment start or randomization). Maintenance therapy is permitted throughout the study (e.g. lenalidomide, interferon)

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label pilot group<br>Twice weekly administration of NOX-H94 | Drug: NOX-H94<br>* intravenous injection<br>* Other names: lexaptepid pegol;Drug: Placebo solution<br>* intravenous injection<br>* Other names: Glucose 5%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of anemia | • Hb increase ≥1 g/dL OR reticulocyte index normalization (≥1%) at any time point until 1 week after the end of treatment AND absence of all of the following treatment failure criteria until 1 week after the end of treatment: Erythrocyte transfusion, ESA or IV iron, Hb drop by ≥1 g/dL Treatment interruption due to adverse events (AEs) | treatment start to 1 week after treatment end | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | Proportion of treatment responders at study visits V4, V6, V8, and V10 to V14, as defined for the primary efficacy endpoint | Treatment start to 8 weeks after end of treatment | 
| Failure | Proportion of treatment failures at study visits V4, V6, V8, and V10, as defined for the primary efficacy endpoint | Treatment start to 1 week after end of treatment | 
| Safety and tolerability | Adverse events, Safety signals derived from laboratory diagnostics, vital signs. | Treatment start to 8 weeks after end of treatment | 
| Pharmacokinetics | NOX-H94 plasma concentrations | Treatment start to 8 weeks after end of treatment | 
| Reticulocytes | Absolute values and change from baseline | Treatment start until 8 weeks after end of treatment | 
| Red blood cells | Absolute values and change from baseline | Treatment start until 8 weeks after end of treatment | 
| Transferrin | Absolute concentrations and change from baseline | Treatment start to 8 weeks after end of treatment | 
| Serum iron | Absolute concentrations and change from baseline | Treatment start to 8 weeks after end of treatment | 
| Ferritin | Absolute concentrations and change from baseline | Treatment start to 8 weeks after end of treatment | 
| Transferrin saturation | Absolute concentrations and change from baseline | Treatment start to 8 weeks after end of treatment | 
| Hemoglobin | Absolute concentrations and change from baseline | Treatment start to 8 weeks after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Hepcidin, Iron, Anemia of Chronic Disease, Anemia, Cancer, Interleukin-6, Iron restriction, CLL, Multiple Myeloma, Hodgkin, anti-hepcidin