Brief Summary
This is a two-part, phase 2b and phase 3 combined prospective, interventional, multicenter, randomized, double-blind, placebo-controlled study.
Part 1: Phase 2b is a dose-finding study for CSL300 vs placebo. Part 2: Phase 3 aims to assess the efficacy of CSL300 vs placebo on cardiovascular (CV) outcomes and safety in subjects with systemic inflammation and either atherosclerotic cardiovascular disease (ASCVD) or diabetes with end stage kidney disease (ESKD) undergoing maintenance dialysis.
Part 1: Phase 2b is a dose-finding study for CSL300 vs placebo. Part 2: Phase 3 aims to assess the efficacy of CSL300 vs placebo on cardiovascular (CV) outcomes and safety in subjects with systemic inflammation and either atherosclerotic cardiovascular disease (ASCVD) or diabetes with end stage kidney disease (ESKD) undergoing maintenance dialysis.
Brief Title
Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis (POSIBIL6ESKD)
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
+1 610-878-4697
Central Contact Email
clinicaltrials@cslbehring.com
Completion Date
Completion Date Type
Estimated
Conditions
END STAGE KIDNEY DISEASE
Eligibility Criteria
Inclusion Criteria:
* Male or female at least 18 years of age.
* A diagnosis of ESKD undergoing maintenance dialysis for at least 12 weeks.
* Serum hs-CRP ≥ 2.0 mg/L.
* A diagnosis of diabetes mellitus OR ASCVD.
Exclusion Criteria:
* Subjects who participated in Part 1 (phase 2b) are not eligible to participate in Part 2 (phase 3).
* Concomitant use of systemic immunosuppressant drugs.
* Part 1 (Phase 2b) excludes subjects with a positive TB or a history of latent TB, whereas Part 2 (Phase 3) excludes active TB but allows inclusion of subjects with a latent TB and at least 4 weeks of prophylactic TB treatment.
* Abnormal LFTs.
* Any life-threatening disease expected to result in death within 12 months.
* A history of GI perforation, inflammatory bowel disease (except fully excised. ulcerative colitis), or peptic ulcer disease.
* Clinically significant active infection or history of opportunistic or invasive fungal infection.
* Male or female at least 18 years of age.
* A diagnosis of ESKD undergoing maintenance dialysis for at least 12 weeks.
* Serum hs-CRP ≥ 2.0 mg/L.
* A diagnosis of diabetes mellitus OR ASCVD.
Exclusion Criteria:
* Subjects who participated in Part 1 (phase 2b) are not eligible to participate in Part 2 (phase 3).
* Concomitant use of systemic immunosuppressant drugs.
* Part 1 (Phase 2b) excludes subjects with a positive TB or a history of latent TB, whereas Part 2 (Phase 3) excludes active TB but allows inclusion of subjects with a latent TB and at least 4 weeks of prophylactic TB treatment.
* Abnormal LFTs.
* Any life-threatening disease expected to result in death within 12 months.
* A history of GI perforation, inflammatory bowel disease (except fully excised. ulcerative colitis), or peptic ulcer disease.
* Clinically significant active infection or history of opportunistic or invasive fungal infection.
Inclusion Criteria
Inclusion Criteria:
* Male or female at least 18 years of age.
* A diagnosis of ESKD undergoing maintenance dialysis for at least 12 weeks.
* Serum hs-CRP ≥ 2.0 mg/L.
* A diagnosis of diabetes mellitus OR ASCVD.
* Male or female at least 18 years of age.
* A diagnosis of ESKD undergoing maintenance dialysis for at least 12 weeks.
* Serum hs-CRP ≥ 2.0 mg/L.
* A diagnosis of diabetes mellitus OR ASCVD.
Gender
All
Gender Based
false
Keywords
End Stage Kidney Disease (ESKD)
Myocardial infarction (MI)
Atherosclerotic cardiovascular disease (ASCVD)
Coronary artery disease
Peripheral artery disease
Diabetes
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05485961
Org Class
Industry
Org Full Name
CSL Behring
Org Study Id
CSL300_2301
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 2b / 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Combined Dose-Finding and Cardiovascular Outcome Study to Investigate the Efficacy and Safety of CSL300 (Clazakizumab) in Subjects With End Stage Kidney Disease Undergoing Dialysis
Primary Outcomes
Outcome Measure
Change from Baseline on the log scale in high-sensitivity C-reactive protein (hs-CRP)(Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Time to first occurrence of CV death or myocardial infarction (MI) (Phase 3)
Outcome Time Frame
Approximately 5 years
Secondary Ids
Secondary Id
2022-500273-14-00
Secondary Outcomes
Outcome Time Frame
Week 12
Outcome Measure
Percent of participants achieving hs-CRP less than (<) 2.0 milligram per Liter (mg/L) (Phase 2b)
Outcome Time Frame
Baseline and up to Week 24
Outcome Measure
Change from baseline in log-transformed hs-CRP (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in serum amyloid A (SAA) (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in secretory phospholipase A2 (sPLA2) (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in fibrinogen (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in plasminogen activator inhibitor -1 (PAI-1) (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in lipoprotein (Lp) (a) (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in albumin (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in Hepcidin (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in hemoglobin (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in erythropoiesis-stimulating agents (ESA) (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in erythropoietin-resistance index (ERI) (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in iron (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in total iron binding capacity (TIBC) (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in transferrin saturation (TSAT) (Phase 2b)
Outcome Time Frame
Baseline and up to Week 12
Outcome Measure
Mean change from Baseline in ferritin (Phase 2b)
Outcome Time Frame
Up to Week 24
Outcome Measure
Area under the plasma concentration versus time curve (AUC) for CSL300 (Phase 2b)
Outcome Time Frame
Up to Week 24
Outcome Measure
Peak Plasma Concentration (Cmax) for CSL300 (Phase 2b)
Outcome Time Frame
Up to Week 24
Outcome Measure
Trough Plasma Concentration (Ctrough) for CSL300 (Phase 2b)
Outcome Time Frame
Up to Week 24
Outcome Measure
Time to Maximum Plasma Concentration (Tmax) for CSL300 (Phase 2b)
Outcome Time Frame
Up to Week 32
Outcome Measure
Percent of participants with adverse events (AE), serious AE (SAE), including adverse events of special interest (AESIs) (Phase 2b)
Outcome Time Frame
Up to Week 12
Outcome Measure
Mean change from Baseline in white blood cell (WBC) (Phase 2b)
Outcome Time Frame
Up to Week 12
Outcome Measure
Mean change from Baseline in neutrophils (Phase 2b)
Outcome Time Frame
Up to Week 12
Outcome Measure
Mean change from Baseline in platelets (Phase 2b)
Outcome Time Frame
Up to Week 12
Outcome Measure
Mean change from Baseline in aspartate aminotransferase (AST) (Phase 2b)
Outcome Time Frame
Up to Week 12
Outcome Measure
Mean change from Baseline in alanine aminotransferase (ALT) (Phase 2b)
Outcome Time Frame
Up to Week 12
Outcome Measure
Mean change from Baseline in total bilirubin (Phase 2b)
Outcome Description
Lipid panel consists of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride.
Outcome Time Frame
Up to Week 12
Outcome Measure
Mean change from Baseline in lipid panel (Phase 2b)
Outcome Time Frame
Up to Week 12
Outcome Measure
Titer of confirmed antibodies specific to CSL300 (Phase 2b)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of all-cause death or MI (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of CV death, MI, or ischemic stroke (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of CV death (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of CV death, MI or major adverse limb event (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of all-cause death (Phase 3)
Outcome Time Frame
Up to 5 years
Outcome Measure
Time to first occurrence of CV death, MI, or hospitalization for heart failure (HF) (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Total number of CV hospitalizations (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Total number of HF hospitalizations and urgent visits (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Total number of hospitalizations (Phase 3)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Matthew Abramowitz
Investigator Email
matthew.abramowitz@einsteinmed.org
Categories Mesh Debug
Heart/Cardiovascular --- MYOCARDIAL INFARCTION
Blood Disorders --- CORONARY ARTERY DISEASE
Heart/Cardiovascular --- CORONARY ARTERY DISEASE
Diabetes --- DIABETES MELLITUS
Diabetes & Endocrine System --- DIABETES MELLITUS
Kidney & Urinary Tract --- RENAL INSUFFICIENCY, CHRONIC
Kidney & Urinary Tract --- KIDNEY DISEASES
Kidney & Urinary Tract --- UROLOGIC DISEASES
Heart/Cardiovascular --- MYOCARDIAL ISCHEMIA
Brain, Spinal Cord & Nervous System --- HEART DISEASES
Heart/Cardiovascular --- HEART DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- VASCULAR DISEASES
Heart/Cardiovascular --- INFARCTION
Heart/Cardiovascular --- ISCHEMIA
Heart/Cardiovascular --- ARTERIOSCLEROSIS
Heart/Cardiovascular --- ARTERIAL OCCLUSIVE DISEASES
Diabetes --- GLUCOSE METABOLISM DISORDERS
Diabetes & Endocrine System --- GLUCOSE METABOLISM DISORDERS
Diabetes --- METABOLIC DISEASES
Diabetes & Endocrine System --- METABOLIC DISEASES
Diabetes --- ENDOCRINE SYSTEM DISEASES
Diabetes & Endocrine System --- ENDOCRINE SYSTEM DISEASES
MeSH Terms
KIDNEY FAILURE, CHRONIC
MYOCARDIAL INFARCTION
ATHEROSCLEROSIS
CORONARY ARTERY DISEASE
PERIPHERAL ARTERIAL DISEASE
DIABETES MELLITUS
RENAL INSUFFICIENCY, CHRONIC
RENAL INSUFFICIENCY
KIDNEY DISEASES
UROLOGIC DISEASES
FEMALE UROGENITAL DISEASES
FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS
UROGENITAL DISEASES
MALE UROGENITAL DISEASES
CHRONIC DISEASE
DISEASE ATTRIBUTES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
MYOCARDIAL ISCHEMIA
HEART DISEASES
CARDIOVASCULAR DISEASES
VASCULAR DISEASES
INFARCTION
ISCHEMIA
NECROSIS
ARTERIOSCLEROSIS
ARTERIAL OCCLUSIVE DISEASES
CORONARY DISEASE
PERIPHERAL VASCULAR DISEASES
GLUCOSE METABOLISM DISORDERS
METABOLIC DISEASES
NUTRITIONAL AND METABOLIC DISEASES
ENDOCRINE SYSTEM DISEASES
CLAZAKIZUMAB