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

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.

Study Overview

• Status: Completed
• Conditions: Anemia, Iron-Deficiency
• Intervention / Treatment: Biological: CSJ137; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Biological: CSJ137; 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.
Placebo Comparator: 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).	Drug: Placebo; Subjects will be dosed with a matching placebo (vehicle control) via up to 30 minutes intravenous infusion.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CCSJ137X2201 from the Novartis Clinical Trials Website
• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2015
• Primary Completion (Actual): May 13, 2020
• Study Completion (Actual): May 13, 2020

Study Registration Dates

• First Submitted: September 29, 2015
• First Submitted That Met QC Criteria: October 6, 2015
• First Posted (Estimate): October 7, 2015

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Anemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia
• Other Study ID Numbers: CCSJ137X2201; 2017-002926-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No