A Two-part Single- and Repeat-dose Study of CSJ137 in Anemic Chronic Hemodialysis Patients

Study Overview
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Brief Summary
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The study will assess the safety, tolerability and efficacy of CSJ137 in chronic hemodialysis patients. It is hypothesized that treatment with CSJ137 may improve the level of hemoglobin in patients on chronic hemodialysis with iron-restricted anemia while reducing the need for dosing with erythropoietin and intravenous iron in these patients.

Detailed Description
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This posting discloses information about Part 1 of CCSJ137X2201. Another part, Part 2, of this trial was planned for conduct subsequent to the initiation of Part 1 and would have a different design than Part 1. However, due to internal strategic non-safety related decision, Part 2 is not going to be conducted and the trial will be terminated after Part 1.

Official Title
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A First-in-human, Two-part (Open Label, and Randomized/Double Blind/Placebo Controlled), Single- and Repeat-dose Study of CSJ137 in Erythropoietin-treated Chronic Hemodialysis Patients With Functional Iron-deficiency Anemia

Conditions
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Anemia, Iron-Deficiency

Intervention / Treatment
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* Biological: CSJ137
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hemodialysis-dependent for at least 2 months prior to screening. Receiving hemodialysis at least 2 times per week Receiving erythropoietin (EPO) therapy. Hemoglobin (Hgb) ≥ 8.5 and < 11.5 g/dL at screening. Ferritin >500 ng/mL and ≤ 2000 ng/mL at screening. TSAT ≤ 50% at a minimum of one time point during the 90 days prior to baseline. Exclusion Criteria: Known diagnosis of hemochromatosis, bone marrow malignancy, lymphatic malignancy or myelodysplastic syndrome. History of dialysis AV fistula thrombosis within 2 months prior to screening, or 2 or more episodes of AV fistula thrombosis within 6 months prior to screening. Liver disease/dysfunction (Child-Pugh score ≥ 6), prior liver transplant, heart failure (NYHA Class III or IV); gastrointestinal bleeding. A positive Hepatitis B surface antigen test result. Patients with Hepatitis C Virus (HCV) infection may be included if all other liver function eligibility criteria are met. ALT, AST or bilirubin ≥ 1.5x ULN within 4 weeks prior to baseline. Uncontrolled renal osteodystrophy Conditions predisposing to an increased risk of serious infection, such as an indwelling vascular catheter (central venous line or non-tunneled/acute hemodialysis catheter) or active infection requiring antibiotic therapy at any time during the 2 weeks prior to screening. Tunneled hemodialysis catheters, and other permanent catheters are permitted. Blood transfusion administered within 4 weeks prior to baseline. Patients who received CSJ137 dose in the past. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSJ137<br>In Part 1 up to 48 subjects will receive a single dose of CSJ137. In Part 2, up to 40 patients will be randomized to one of 2 arms with equal allocation: one CSJ137 dose arm from Part 1 and a placebo arm. Each patient in Part 2 will receive up to 2 doses (repeat dose). | Biological: CSJ137<br>* Starting dose is 0.010 mg/kg and dose escalation will proceed with semi-log increase steps to a maximum dose level 10 mg/kg. Subjects receive the treatment via up to 30 minutes intravenous infusion.<br>|
| Placebo Comparator: Placebo<br>In Part 2, up to 40 patients will be randomized to one of 2 arms with equal allocation: one CSJ137 dose arm from Part 1 and a placebo arm. Each patient in Part 2 will receive up to 2 doses (repeat dose). | Drug: Placebo<br>* Subjects will be dosed with a matching placebo (vehicle control) via up to 30 minutes intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | safety and tolerability following administration of CSJ137 | baseline through 115 days after CSJ137 is administered | 
| Minimum active dose of CSJ137 determined by assessment of levels of hemoglobin in blood, without evidence of liver dysfunction or other safety concerns. | to determine the minimum dose of CSJ137 that is active for treatment | Hemoglobin response at 28 days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak concentration (Cmax) of CSJ137 in serum | to assess the concentration of CSJ137 in the body over time | before CSJ137 is administered, then 0.5 hours and 6 hours after CSJ137 is administered on Day 1. Also 1, 2, 3, 5, 12, 19, 28, and 84 days after CSJ137 is administered | 
| Area under the serum concentration versus time curve (AUC) | to assess the concentration of CSJ137 in the body over time | before CSJ137 is administered, then 0.5 hours and 6 hours after CSJ137 is administered on Day 1. Also 1, 2, 3, 5, 12, 19, 28, and 84 days after CSJ137 is administered | 

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