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

Phase 1

Completed

• Conditions: Anemia, Iron-Deficiency
• Interventions: Biological: CSJ137; Drug: Placebo

• Registration Number: NCT02570854
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

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.

Study Timeline

• Study Start: 2015-09-22
• Study First Submitted: 2015-09-29
• Study First Submitted QC: 2015-10-06
• Study First Posted: 2015-10-07
• Primary Completion: 2020-05-13
• Study Completion: 2020-05-13
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-07
• Last Update Posted: 2021-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Hemodialysis-dependent for at least 2 months prior to screening.
2. Receiving hemodialysis at least 2 times per week
3. Receiving erythropoietin (EPO) therapy.
4. Hemoglobin (Hgb) ≥ 8.5 and < 11.5 g/dL at screening.
5. Ferritin >500 ng/mL and ≤ 2000 ng/mL at screening.
6. TSAT ≤ 50% at a minimum of one time point during the 90 days prior to baseline.

Exclusion Criteria

1. Known diagnosis of hemochromatosis, bone marrow malignancy, lymphatic malignancy or myelodysplastic syndrome.
2. 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.
3. Liver disease/dysfunction (Child-Pugh score ≥ 6), prior liver transplant, heart failure (NYHA Class III or IV); gastrointestinal bleeding.
4. 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.
5. ALT, AST or bilirubin ≥ 1.5x ULN within 4 weeks prior to baseline.
6. Uncontrolled renal osteodystrophy
7. 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.
8. Blood transfusion administered within 4 weeks prior to baseline.
9. Patients who received CSJ137 dose in the past.

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CSJ137	CSJ137	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).
Placebo	Placebo	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Peak concentration (Cmax) of CSJ137 in serum	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	to assess the concentration of CSJ137 in the body over time
Area under the serum concentration versus time curve (AUC)	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	to assess the concentration of CSJ137 in the body over time

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 London, United Kingdom