Clinical trial NCT01691040: Efficacy of NOX-H94 on Anemia of Chronic Disease in Patients With Cancer
Official title: Phase IIa Study to Characterize the Effects of the Spiegelmer® NOX H94 on Anemia of Chronic Disease in Patients With Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia of Chronic Disease
Keywords: Hepcidin
Iron
Anemia of Chronic Disease
Anemia
Cancer
Interleukin-6
Iron restriction
Lymphoma
CLL
Multiple Myeloma
Hodgkin
anti-hepcidin
Lead sponsor: TME Pharma AG
Sponsor class: INDUSTRY
First posted: 2012-09-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Response rate of anemia
timeFrame: treatment start to 1 week after treatment end
Secondary outcomes:
measure: Response
timeFrame: Treatment start to 8 weeks after end of treatment
measure: Failure
timeFrame: Treatment start to 1 week after end of treatment
measure: Safety and tolerability
timeFrame: Treatment start to 8 weeks after end of treatment
measure: Pharmacokinetics
timeFrame: Treatment start to 8 weeks after end of treatment
measure: Reticulocytes
timeFrame: Treatment start until 8 weeks after end of treatment
measure: Red blood cells
timeFrame: Treatment start until 8 weeks after end of treatment
measure: Transferrin
timeFrame: Treatment start to 8 weeks after end of treatment
measure: Serum iron
timeFrame: Treatment start to 8 weeks after end of treatment
measure: Ferritin
timeFrame: Treatment start to 8 weeks after end of treatment
measure: Transferrin saturation
timeFrame: Treatment start to 8 weeks after end of treatment
measure: Hemoglobin
timeFrame: Treatment start to 8 weeks after end of treatment
Other outcomes:
measure: Exploratory analyses
timeFrame: Treatment start to 1 week after end of treatment
measure: Exploratory analyses
timeFrame: Treatment start to 1 week after end of treatment
Locations:
city: Graz
country: Austria
facility: University Hospital
city: Vienna
country: Austria
facility: AKH Vienna
city: Vienna
country: Austria
facility: Wilhelminenspital
city: Plovdiv
country: Bulgaria
facility: University Hospital
city: Sofia
country: Bulgaria
facility: Tokuda Hospital
city: Varna
country: Bulgaria
facility: University Hospital
city: Brasov
country: Romania
facility: Spitalul Judetean
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic
city: Craiova
country: Romania
facility: Spitalul Municipal
city: Targu-Mures
country: Romania
facility: Spitalul Judetean
city: Timisoara
country: Romania
facility: Oncomed
Study officials:
affiliation: TME Pharma AG
name: Kai Riecke, MD
role: STUDY_DIRECTOR
References:
citation: 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.