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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NOXXON Pharma AG
ClinicalTrials.gov Identifier:
NCT01691040
First received: September 4, 2012
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Anemia of Chronic Disease
Drug: NOX-H94
Drug: Placebo solution
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IIa Study to Characterize the Effects of the Spiegelmer® NOX H94 on Anemia of Chronic Disease in Patients With Cancer

Resource links provided by NLM:


Further study details as provided by NOXXON Pharma AG:

Primary Outcome Measures:
  • Response rate of anemia [ Time Frame: treatment start to 1 week after treatment end ] [ Designated as safety issue: Yes ]

    • 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:
  • Response [ Time Frame: Treatment start to 8 weeks after end of treatment ] [ Designated as safety issue: Yes ]
    Proportion of treatment responders at study visits V4, V6, V8, and V10 to V14, as defined for the primary efficacy endpoint

  • Failure [ Time Frame: Treatment start to 1 week after end of treatment ] [ Designated as safety issue: Yes ]
    Proportion of treatment failures at study visits V4, V6, V8, and V10, as defined for the primary efficacy endpoint

  • Safety and tolerability [ Time Frame: Treatment start to 8 weeks after end of treatment ] [ Designated as safety issue: Yes ]
    Adverse events, Safety signals derived from laboratory diagnostics, vital signs.

  • Pharmacokinetics [ Time Frame: Treatment start to 8 weeks after end of treatment ] [ Designated as safety issue: No ]
    NOX-H94 plasma concentrations

  • Reticulocytes [ Time Frame: Treatment start until 8 weeks after end of treatment ] [ Designated as safety issue: No ]
    Absolute values and change from baseline

  • Red blood cells [ Time Frame: Treatment start until 8 weeks after end of treatment ] [ Designated as safety issue: Yes ]
    Absolute values and change from baseline

  • Transferrin [ Time Frame: Treatment start to 8 weeks after end of treatment ] [ Designated as safety issue: No ]
    Absolute concentrations and change from baseline

  • Serum iron [ Time Frame: Treatment start to 8 weeks after end of treatment ] [ Designated as safety issue: No ]
    Absolute concentrations and change from baseline

  • Ferritin [ Time Frame: Treatment start to 8 weeks after end of treatment ] [ Designated as safety issue: No ]
    Absolute concentrations and change from baseline

  • Transferrin saturation [ Time Frame: Treatment start to 8 weeks after end of treatment ] [ Designated as safety issue: No ]
    Absolute concentrations and change from baseline

  • Hemoglobin [ Time Frame: Treatment start to 8 weeks after end of treatment ] [ Designated as safety issue: Yes ]
    Absolute concentrations and change from baseline


Other Outcome Measures:
  • Exploratory analyses [ Time Frame: Treatment start to 1 week after end of treatment ] [ Designated as safety issue: No ]
    Soluble transferrin receptor

  • Exploratory analyses [ Time Frame: Treatment start to 1 week after end of treatment ] [ Designated as safety issue: No ]
    Reticulocyte hemoglobin content


Enrollment: 12
Study Start Date: September 2012
Study Completion Date: December 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open-label pilot group
Twice weekly administration of NOX-H94
Drug: NOX-H94
intravenous injection
Other Name: lexaptepid pegol
Drug: Placebo solution
intravenous injection
Other Name: Glucose 5%

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01691040

Locations
Austria
University Hospital
Graz, Austria, 8036
Wilhelminenspital
Vienna, Austria, 1160
AKH Vienna
Vienna, Austria, 1090
Bulgaria
University Hospital
Plovdiv, Bulgaria, 4000
Tokuda Hospital
Sofia, Bulgaria, 1407
University Hospital
Varna, Bulgaria, 9010
Romania
Spitalul Judetean
Brasov, Romania, 500326
Institutul Oncologic
Cluj-Napoca, Romania, 400124
Spitalul Municipal
Craiova, Romania, 208028
Spitalul Judetean
Targu-Mures, Romania, 540136
Oncomed
Timisoara, Romania, 300239
Sponsors and Collaborators
NOXXON Pharma AG
Investigators
Study Director: Kai Riecke, MD NOXXON Pharma AG
  More Information

No publications provided

Responsible Party: NOXXON Pharma AG
ClinicalTrials.gov Identifier: NCT01691040     History of Changes
Other Study ID Numbers: SNOXH94C201, 2012-001525-27
Study First Received: September 4, 2012
Last Updated: June 25, 2014
Health Authority: Austria: Federal Office for Safety in Health Care
Romania: National Agency for Medicines and Medical Devices
Bulgaria: Bulgarian Drug Agency

Keywords provided by NOXXON Pharma AG:
Hepcidin
Iron
Anemia of Chronic Disease
Anemia
Cancer
Interleukin-6
Iron restriction
Lymphoma
CLL
Multiple Myeloma
Hodgkin
anti-hepcidin

Additional relevant MeSH terms:
Anemia
Chronic Disease
Hematologic Diseases
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on July 26, 2014