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

Phase 2

Completed

• Conditions: Anemia of Chronic Disease
• Interventions: Drug: NOX-H94; Drug: Placebo solution

• Registration Number: NCT01691040
• Lead Sponsor: TME Pharma AG

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-09
• Study First Submitted: 2012-09-04
• Study First Submitted QC: 2012-09-19
• Study First Posted: 2012-09-24
• Primary Completion: 2013-11
• Study Completion: 2013-12
• Status Verified: 2014-06
• Last Update Submitted: 2014-06-25
• Last Update Posted: 2014-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Open-label pilot group	NOX-H94	Twice weekly administration of NOX-H94
Open-label pilot group	Placebo solution	Twice weekly administration of NOX-H94

Primary Outcome Measures

Name	Time	Method
Response rate of anemia	treatment start to 1 week after treatment end	• 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)

Secondary Outcome Measures

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

Trial Locations

Locations (8)

AKH Vienna; 🇦🇹 Vienna, Austria

Wilhelminenspital; 🇦🇹 Vienna, Austria

Tokuda Hospital; 🇧🇬 Sofia, Bulgaria

Spitalul Municipal; 🇷🇴 Craiova, Romania

University Hospital; 🇧🇬 Varna, Bulgaria

Oncomed; 🇷🇴 Timisoara, Romania

Institutul Oncologic; 🇷🇴 Cluj-Napoca, Romania

Spitalul Judetean; 🇷🇴 Targu-Mures, Romania