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

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

Sponsors

Lead Sponsor: Novartis Pharmaceuticals

Source Novartis
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.

Overall Status Completed
Start Date September 22, 2015
Completion Date May 13, 2020
Primary Completion Date May 13, 2020
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 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. Hemoglobin response at 28 days post-dose
Secondary Outcome
Measure Time Frame
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
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
Enrollment 40
Condition
Intervention

Intervention Type: Biological

Intervention Name: CSJ137

Description: 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.

Arm Group Label: CSJ137

Intervention Type: Drug

Intervention Name: Placebo

Description: Subjects will be dosed with a matching placebo (vehicle control) via up to 30 minutes intravenous infusion.

Arm Group Label: Placebo

Eligibility

Criteria:

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Location
Facility:
Novartis Investigative Site | San Diego, California, 91942, United States
Novartis Investigative Site | Lakewood, Colorado, 80228, United States
Novartis Investigative Site | Orlando, Florida, 32809, United States
Novartis Investigative Site | Minneapolis, Minnesota, 55404, United States
Novartis Investigative Site | Chattanooga, Tennessee, 37404, United States
Novartis Investigative Site | Praha, 12808, Czechia
Novartis Investigative Site | Ashkelon, 78278, Israel
Novartis Investigative Site | Hadera, 38100, Israel
Novartis Investigative Site | Jerusalem, 91120, Israel
Novartis Investigative Site | Petach Tikva, 49100, Israel
Novartis Investigative Site | Ramat Gan, Israel
Novartis Investigative Site | Tel Aviv, 62439, Israel
Novartis Investigative Site | London, SW17 0QT, United Kingdom
Location Countries

Czechia

Israel

United Kingdom

United States

Verification Date

May 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: CSJ137

Type: Experimental

Description: 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).

Label: Placebo

Type: Placebo Comparator

Description: 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).

Patient Data Undecided
Study Design Info

Allocation: Randomized

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov