Combined Dose-Finding and CV Outcomes Study with CSL300 (Clazakizumab) in Adult Subjects with ESKD Undergoing Dialysis (POSIBIL6ESKD).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CSL Behring LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

17 Jul 2023 → ongoing

Decision date (initial)

2024-02-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2022-500273-14-00

ClinicalTrials.gov

NCT05485961

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of different intravenous doses of CSL300 in subjects with ESKD undergoing maintenance dialysis on reduction of high-sensitivity C-reactive protein (hs-CRP).

Conditions and MedDRA coding

Atherosclerotic cardiovascular disease in patients with ESKD

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers.  For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at [email protected].

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Male or female at least 18 years of age.
2. A diagnosis of End Stage Kidney Diseas (ESKD) undergoing maintenance dialysis for at least 12 weeks
3. Serum hs-CRP ≥ 2.0 mg/L.
4. A diagnosis of diabetes mellitus OR Atherosclerotic Cardiovascular Disease (ASCVD)

Exclusion criteria 6

1. Subjects who participated in Part 1 (phase 2b) are not eligible to participate in Part 2 (phase 3).
2. Concomitant use of systemic immunosuppressant drugs.
3. Abnormal LFTs.
4. Any life-threatening disease expected to result in death within 12 months.
5. A history of GI perforation, inflammatory bowel disease (except fully excised ulcerative colitis), or peptic ulcer disease.
6. Clinically significant active infection or history of opportunistic or invasive fungal infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change from Baseline on the log scale in hs-CRP (Phase 2b).
2. Time to first occurrence of CV death or myocardial infarction (MI) (Phase 3).

Secondary endpoints 16

1. Percent of subjects achieving hs‑CRP less than (<) 2.0 milligram per Liter (mg/L) (Phase 2b).
2. Change from baseline in log-transformed hs‑CRP (Phase 2b).
3. Mean change from Baseline in serum amyloid A (SAA), secretory phospholipase A2 (sPLA2), fibrinogen, plasminogen activator inhibitor -1 (PAI-1), lipoprotein (a) [Lp (a)] and albumin (Phase 2b)
4. Mean change from Baseline in Hepcidin, hemoglobin, erythropoiesis stimulating agent (ESA), erythropoietin resistance index (ERI), iron, total iron-binding capacity (TIBC), transferrin saturation (TSAT), ferritin (Phase 2b)
5. Area under the plasma concentration versus time curve (AUC), peak plasma concentration (Cmax), trough plasma concentration (Ctrough), and time to maximum plasma concentration (Tmax) (Phase 2b)
6. Percent of subjects with adverse event (AE), serious AE (SAE), including AEs of special interest (AESIs) (Phase 2b)
7. Mean change from Baseline in white blood cell (WBC), neutrophil, platelets, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin; lipid panel: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and Immunogenicity (Phase 2b)
8. Time to first occurrence of all-cause death or MI (Phase 3).
9. Time to first occurrence of CV death, MI, or ischemic stroke (Phase 3).
10. Time to first occurrence of CV death (Phase 3).
11. Time to first occurrence of CV death, MI or major adverse limb event (Phase 3).
12. Time to first occurrence of all-cause death (Phase 3).
13. Time to first occurrence of CV death, MI, or hospitalization for heart failure (HF) (Phase 3).
14. Total number of CV hospitalizations (Phase 3).
15. Total number of HF hospitalizations and urgent visits (Phase 3).
16. Total number of hospitalizations (Phase 3).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CSL Behring LLC

Sponsor organisation

CSL Behring LLC

Address

1020 1st Avenue

City

King Of Prussia

Postcode

19406-1310

Country

United States

Scientific contact point

Organisation

CSL Behring LLC

Contact name

Trial Registration Coordinator

Public contact point

Organisation

CSL Behring LLC

Contact name

Trial Registration Coordinator

Third parties 14

Locations

23 EU/EEA countries · 214 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 242 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

38 submissions — initial application plus substantial / non-substantial modifications