Clinical trial NCT02079896: Lexaptepid Pegol (NOX-H94) in ESA-hyporesponsive Anemia in Dialysis Patients
Official title: Safety, PK/PD, and Efficacy of NOX-H94 in Dialysis Patients With ESA-hyporesponsive Anemia: A Randomized, Double Blind, Placebo Controlled Parallel Group Study With a Single Blind Cross-over Group
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Anemia
End Stage Renal Disease
Keywords: Dialysis
Lead sponsor: TME Pharma AG
Sponsor class: INDUSTRY
First posted: 2014-03-06
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Dialysis patients regularly suffer from anemia which may be caused by various contributing factors, alone or in combination, including blood loss, low erythropoietin and iron sequestration. In most patients, the anemia is responsive to treatment with erythropoietin or other erythropoiesis stimulating agents (ESA) alone or in combination with intravenous (i.v.) iron. In about 10% of patients however, the anaemia does not respond appropriately to this standard treatment and high to very high doses of ESA and i.v. iron are used to maintain acceptable hemoglobin concentrations. In these patients, hepcidin was identified as a causative factor leading to anemia of chronic disease with functional iron deficiency and ESA-hyporesponsiveness.

The Spiegelmer lexaptepid pegol (NOX-H94) offers a hepcidin-specific approach to the treatment of anemia of chronic disease. The safety and the activity of lexaptepid pegol are supported by data from healthy subjects and patients with multiple myeloma or lymphoma. The present study in dialysis patients with functional iron deficiency and ESA-hyporesponsiveness is conducted to demonstrate the safety of lexaptepid pegol in this population, to investigate its pharmacokinetic (PK) and pharmacodynamic (PD) profiles and its efficacy in increasing haemoglobin (Hb) in dialysis patients.


Eligibility criteria: Inclusion Criteria:

* End stage renal disease treated with maintenance hemodialysis.
* Anemia : Hb 7 to 11 g/dL.
* Functional iron deficiency: Transferrin saturation \<30%, Ferritin ≥300 ng/mL.
* ESA-hyporesponsiveness with erythropoietin dose ≥12,000 IU/ week.

Exclusion Criteria:

* Treatment with darbepoetin or methoxy-polyethyleneglycol-epoetin.
* Uncontrolled / unstable cardiovascular , peripheral arterial or cerebrovascular disease.
* Congestive heart failure: New York Heart Association Class III or IV.
* Unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty/stents, or coronary artery bypass grafting \<3 months prior screening.
* Any other medical conditions requiring a change in treatment within 4 weeks prior to screening or making study participation unadvisable.
* History of clinically relevant hemolysis and/or blood loss.
* AST, ALT, or bilirubin ≥2.0 times the upper limit of normal.
* Known bone marrow fibrosis.
* Treatment with i.v. iron \<4 weeks prior to screening or during the screening period or change in erythropoietin dose during last month.
* Any acute or chronic infection, viral or bacterial within 4 weeks prior to screening or during the screening period considered as systemic infection.

Primary outcomes:
measure: Number of adverse events
timeFrame: up to 8 weeks
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: Weeks 1, 2, 3, 4, 5, 6, 8
measure: Pharmacodynamics
timeFrame: 0 to 48 hours
measure: Efficacy
timeFrame: Weeks 1, 2, 3, 4, 5, 6, 8
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: Dialysis Unit
city: Halle
country: Germany
facility: University Hospital
city: Leipzig
country: Germany
facility: Hospital
city: Villingen-Schwenningen
country: Germany
facility: Dialysis Unit
city: Siena
country: Italy
facility: Hospital
city: Swansea
country: United Kingdom
facility: Hospital
state: Wales
city: Leicester
country: United Kingdom
facility: Hospital
city: London
country: United Kingdom
facility: Hospital
city: London
country: United Kingdom
facility: King's College London
city: Stevenage
country: United Kingdom
facility: Lister Hospital
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.