Lexaptepid Pegol (NOX-H94) in ESA-hyporesponsive Anemia in Dialysis Patients

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Anemia, End Stage Renal Disease

Intervention / Treatment
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* Drug: Lexaptepid pegol (NOX-H94)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose cross-over pilot<br>Single dose of lexaptepid pegol (NOX-H94) cross-over with single dose of placebo | Drug: Lexaptepid pegol (NOX-H94)<br>* anti-hepcidin L-RNA-aptamer (Spiegelmer)<br>* Other names: NOX-H94;Drug: Placebo<br> <br> |
| Placebo Comparator: Control<br>Twice weekly doses of placebo, 9 total | Drug: Placebo<br> <br> |
| Experimental: Lexaptepid pegol (NOX-H94)<br>Twice weekly doses of lexaptepid pegol (NOX-H94), 9 total | Drug: Lexaptepid pegol (NOX-H94)<br>* anti-hepcidin L-RNA-aptamer (Spiegelmer)<br>* Other names: NOX-H94;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events |  | up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics | Peak concentrations, systemic exposure, elimination | Weeks 1, 2, 3, 4, 5, 6, 8 | 
| Pharmacodynamics | Change in serum iron concentrations | 0 to 48 hours | 
| Efficacy | Change in hemoglobin | Weeks 1, 2, 3, 4, 5, 6, 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dialysis