A Clinical Study of SCTC21C in Participants With Plasma Cell-driven Autoimmune Diseases

Official title

A Randomized, Double-blind, Placebo-controlled Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SCTC21C in Subjects With Plasma Cell-driven Autoimmune Diseases

Overview

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SCTC21C in subjects with plasma cell-driven autoimmune diseases

Detailed description

This is a randomized, double-blind, placebo-controlled Phase I/II study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of multiple doses of SCTC21C in subjects with plasma cell-driven autoimmune diseases.

In phase 1 study, participants will be assigned to receive sequentially higher doses of SCTC21C to determine the recommended dose of SCTC21C for the randomized dose optimization- stage. In phase 2 study, 2 dose levels will be used. A total of 72 participants will be randomized in a 1:1:1 ration to dose 1, dose 2 or placebo groups to better understand the exposure/efficacy/toxicity relationship.

Interventions

• Biological SCTC21C
  Drug: SCTC21C Administered SC

Primary outcome measures

• Phase 1: Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs). [Time frame: 36 Weeks]
• Phase 2: Percentage change in urine protein-to-creatinine ratio (UPCR) at Week 24 compared to baseline [Time frame: 24 Weeks]

Secondary outcome measures (12)

• Phase 1: Percentage change in urine protein-to-creatinine ratio (UPCR) compared to baseline [Time frame: 36 Weeks]
• Phase 1: Percentage change in 24-hour urinary protein excretion compared to baseline [Time frame: 36 Weeks]
• Phase 1: Percentage change in urine albumin-to-creatinine ratio (UACR) compared to baseline [Time frame: 36 Weeks]
• Phase 1: Percentage change in eGFR compared to baseline [Time frame: 36 Weeks]
• Phase 1: Change from baseline in Immunoglobulin A (IgA), Immunoglobulin M (IgM), Immunoglobulin G (IgG), etc. [Time frame: 36 Weeks]
• Phase 1: C-max [Time frame: 24 Weeks]
• Phase 1: T1/2 [Time frame: 24 Weeks]
• Phase 1: AUC0-t [Time frame: 24 Weeks]
• Phase 1: Percentage of Participants With Positive Antidrug Antibody (ADA) and Neutralizing Antibody (Nab) [Time frame: 36 Weeks]
• Phase 2: Percentage change in urine protein-to-creatinine ratio (UPCR) compared to baseline [Time frame: 104 Weeks]
• Phase 2: Percentage change in 24-hour urinary protein excretion compared to baseline [Time frame: 104 Weeks]
• Phase 2: Percentage change in urine albumin-to-creatinine ratio (UACR) excretion compared to baseline [Time frame: 104 Weeks]

Eligibility criteria

Inclusion criteria

• Age ≥18 years at the time of signing the ICF;
• The subject has been diagnosed with IgA nephropathy through kidney tissue biopsy;
• The subject has been on a stable and maximally tolerated dose of ACEI or ARB (or the maximum allowable dose according to the prescribing information) for at least 12 weeks prior to the first dose. Subjects using both ACEI and ARB simultaneously will not be accepted;
• The estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI formula must be ≥30 mL/min/1.73 m²;
• During the screening period, the subject must have 24-hour proteinuria ≥1.0 g or a urine protein-to-creatinine ratio (UPCR) ≥0.75 g/g based on 24-hour urine protein;
• All male subjects or women of childbearing potential (with a negative blood pregnancy test within 7 days prior to the first dose of investigational drug) must agree to use reliable contraception together with their partner from the time of signing the ICF until 5 months after the last dose of the study drug;
• Understand the study procedures and voluntarily sign the informed consent form in writing.

Exclusion criteria

• IgA nephropathy secondary to other diseases;
• Any kidney disease with special pathological or clinical types, such as nephrotic syndrome, crescentic glomerulonephritis, etc.;
• Use of systemic corticosteroids within the 3 months prior to baseline or expected use during the study period;
• Use of systemic immunosuppressive drugs within the 3 months prior to baseline or expected use during the study period;
• Use of other B-cell-targeting biologics or unapproved investigational biologics within the 6 months prior to baseline;
• Patients who have experienced any of the following cardiovascular events within 24 weeks prior to baseline: myocardial infarction, unstable angina, ventricular arrhythmias, heart failure with NYHA class II or higher, stroke, etc.;
• A history of solid organ or hematopoietic stem cell or bone marrow transplantation, or expected to undergo a transplant procedure during the treatment period with the investigational drug；
• Currently undergoing hemodialysis or peritoneal dialysis, or expected to require hemodialysis or peritoneal dialysis during the treatment period with the investigational drug;
• Any symptoms or signs within 30 days prior to baseline indicating an active infection (excluding the common cold), or requiring systemic anti-infective treatment, or being at high risk for infection;
• Positive viral serology, including HIV, HCV, and HBV, etc.; Hepatitis B patients: active hepatitis or severe liver disease;
• Currently or within the past 5 years has had malignant tumors, except for fully treated skin basal cell carcinoma, squamous cell carcinoma, cervical carcinoma in situ, or cervical intraepithelial neoplasia;
• Known allergy to the active ingredient or excipients of the investigational drug.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 20 centers

• The First Affiliated Hospital of Baotou Medical College — Baotou
• Beijing Tsinghua Changgung Hospital — Beijing
• Peking University First Hospital — Beijing
• Sichuan Academy of Medical Sciences - Sichuan Provincial People's Hospital — Chengdu
• Guangdong Provincial People's Hospital — Guangzhou
• The First Affliated Hospital, Zhejiang University School of Medicine — Hangzhou
• Zhejiang Provincial People's Hospital — Hangzhou
• Shandong Provincial Hospital — Jinan
• … and 12 more centers

Identifiers

NCT: NCT06774664 · SCTC21C-X201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗