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

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

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.

Study Overview

• Status: Completed
• Conditions: Anemia of Chronic Disease
• Intervention / Treatment: Drug: NOX-H94; Drug: Placebo solution

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • University Hospital
  • Vienna, Austria, 1160
    • Wilhelminenspital
  • Vienna, Austria, 1090
    • AKH Vienna
• Bulgaria
  • Plovdiv, Bulgaria, 4000
    • University Hospital
  • Sofia, Bulgaria, 1407
    • Tokuda Hospital
  • Varna, Bulgaria, 9010
    • University Hospital
• Romania
  • Brasov, Romania, 500326
    • Spitalul Judetean
  • Cluj-Napoca, Romania, 400124
    • Institutul Oncologic
  • Craiova, Romania, 208028
    • Spitalul Municipal
  • Targu-Mures, Romania, 540136
    • Spitalul Judetean
  • Timisoara, Romania, 300239
    • Oncomed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Open-label pilot group; Twice weekly administration of NOX-H94	Drug: NOX-H94; intravenous injection; Other Names: lexaptepid pegol; Drug: Placebo solution; intravenous injection; Other Names: Glucose 5%

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory analyses	Soluble transferrin receptor	Treatment start to 1 week after end of treatment
Exploratory analyses	Reticulocyte hemoglobin content	Treatment start to 1 week after end of treatment

Collaborators and Investigators

• Sponsor: TME Pharma AG

Publications and helpful links

General Publications

• Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: September 4, 2012
• First Submitted That Met QC Criteria: September 19, 2012
• First Posted (ESTIMATE): September 24, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): June 26, 2014
• Last Update Submitted That Met QC Criteria: June 25, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Cancer; Multiple Myeloma; Lymphoma; Anemia; Iron; Hepcidin; CLL; Interleukin-6; Hodgkin; Anemia of Chronic Disease; Iron restriction; anti-hepcidin
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Hematologic Diseases; Chronic Disease; Anemia
• Other Study ID Numbers: SNOXH94C201; 2012-001525-27 (EUDRACT_NUMBER)