Clinical trial NCT06774664: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: IgA Nephropathy
Lead sponsor: Sinocelltech Ltd.
Sponsor class: INDUSTRY
First posted: 2025-01-14
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years at the time of signing the ICF;
2. The subject has been diagnosed with IgA nephropathy through kidney tissue biopsy;
3. 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;
4. The estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI formula must be ≥30 mL/min/1.73 m²;
5. 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;
6. 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;
7. Understand the study procedures and voluntarily sign the informed consent form in writing.

Exclusion Criteria:

1. IgA nephropathy secondary to other diseases;
2. Any kidney disease with special pathological or clinical types, such as nephrotic syndrome, crescentic glomerulonephritis, etc.;
3. Use of systemic corticosteroids within the 3 months prior to baseline or expected use during the study period;
4. Use of systemic immunosuppressive drugs within the 3 months prior to baseline or expected use during the study period;
5. Use of other B-cell-targeting biologics or unapproved investigational biologics within the 6 months prior to baseline;
6. 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.;
7. 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；
8. Currently undergoing hemodialysis or peritoneal dialysis, or expected to require hemodialysis or peritoneal dialysis during the treatment period with the investigational drug;
9. 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;
10. Positive viral serology, including HIV, HCV, and HBV, etc.; Hepatitis B patients: active hepatitis or severe liver disease;
11. 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;
12. Known allergy to the active ingredient or excipients of the investigational drug.

Primary outcomes:
measure: Phase 1: Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs).
timeFrame: 36 Weeks
measure: Phase 2: Percentage change in urine protein-to-creatinine ratio (UPCR) at Week 24 compared to baseline
timeFrame: 24 Weeks
Secondary outcomes:
measure: Phase 1: Percentage change in urine protein-to-creatinine ratio (UPCR) compared to baseline
timeFrame: 36 Weeks
measure: Phase 1: Percentage change in 24-hour urinary protein excretion compared to baseline
timeFrame: 36 Weeks
measure: Phase 1: Percentage change in urine albumin-to-creatinine ratio (UACR) compared to baseline
timeFrame: 36 Weeks
measure: Phase 1: Percentage change in eGFR compared to baseline
timeFrame: 36 Weeks
measure: Phase 1: Change from baseline in Immunoglobulin A (IgA), Immunoglobulin M (IgM), Immunoglobulin G (IgG), etc.
timeFrame: 36 Weeks
measure: Phase 1: C-max
timeFrame: 24 Weeks
measure: Phase 1: T1/2
timeFrame: 24 Weeks
measure: Phase 1: AUC0-t
timeFrame: 24 Weeks
measure: Phase 1: Percentage of Participants With Positive Antidrug Antibody (ADA) and Neutralizing Antibody (Nab)
timeFrame: 36 Weeks
measure: Phase 2: Percentage change in urine protein-to-creatinine ratio (UPCR) compared to baseline
timeFrame: 104 Weeks
measure: Phase 2: Percentage change in 24-hour urinary protein excretion compared to baseline
timeFrame: 104 Weeks
measure: Phase 2: Percentage change in urine albumin-to-creatinine ratio (UACR) excretion compared to baseline
timeFrame: 104 Weeks
measure: Phase 2: Percentage change in eGFR compared to baseline
timeFrame: 104 Weeks
measure: Phase 2: Change from baseline in Immunoglobulin A (IgA), Immunoglobulin M (IgM), Immunoglobulin G (IgG), etc.
timeFrame: 104 Weeks
measure: Phase 2: C-max
timeFrame: 32 Weeks
measure: Phase 2: T1/2
timeFrame: 32 Weeks
measure: Phase 2: AUC0-t
timeFrame: 32 Weeks
measure: Phase 2: Percentage of Participants With Positive Antidrug Antibody (ADA) and Neutralizing Antibody (Nab)
timeFrame: 104 Weeks
Other outcomes:
Locations:
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College
city: Beijing
country: China
facility: Beijing Tsinghua Changgung Hospital
city: Beijing
country: China
facility: Peking University First Hospital
city: Chengdu
country: China
facility: Sichuan Academy of Medical Sciences - Sichuan Provincial People's Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Hangzhou
country: China
facility: The First Affliated Hospital, Zhejiang University School of Medicine
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
city: Jinan
country: China
facility: Shandong Provincial Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University
city: Nanning
country: China
facility: Guangxi Zhuang Autonomous Region People's Hospital
city: Ningbo
country: China
facility: Ningbo NO.2 Hospital
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Shanghai General Hospital
city: Wuxi
country: China
facility: Wuxi People's Hospital
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiao Tong University
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xingtai
country: China
facility: The Second Affiliated Hospital of Xingtai Medical College
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
Study officials:
affiliation: Peking University First Hospital, Department of Nephrology
name: Hong Zhang
role: PRINCIPAL_INVESTIGATOR
References: