Phase Ib/IIa Study for IPG11406 in Patients with Lupus Nephritis
- Conditions
- Lupus Nephritis
- Interventions
- Drug: IPG11406
- Registration Number
- NCT06717815
- Lead Sponsor
- Nanjing Immunophage Biotech Co., Ltd
- Brief Summary
A multi-center, multi-dose phase Ib/IIa clinical study evaluating the safety, tolerability, preliminary efficacy, pharmacokinetics, and impact on biomarkers of IPG11406 in patients with Lupus Nephritis
- Detailed Description
This is a multi-center, multi-dose phase Ib/IIa study to evaluate the safety, tolerability, preliminary efficacy, pharmacokinetics, and impact on biomarkers of IPG11406 in patients with Lupus Nephritis.
Part A Three dose groups will be administered with drugs, namely 20 mg bid (cohort 1), 40 mg bid (cohort 2), and 80 mg bid (cohort 3). In cohorts 1 to 3, there will be 9-12 subjects in each cohort. All subjects will undergo screening for 28 days before administration, and those who pass the screening will undergo 28 days of drug administration and observation. This part plans to recruit about 36 patients with Lupus Nephritis.
After each cohort completes 28 days of dosing and evaluation, the Safety Monitoring Committee (SMC) will assess the safety and tolerability of IPG11406 based on all accumulated safety data (including follow-up data) and available pharmacokinetic (PK) data under blinded conditions. Based on the results of the safety and tolerability assessment, the SMC will decide whether to proceed with dosing in the next dose cohort. Part A will determine the recommended phase II dose (RP2D) and maximum tolerated dose (MTD) of IPG11406.
Part B The design of Part B will be finalized based on the results of Part A.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 36
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1 (20 mg, Bid) IPG11406 9\~12 subjects will be orally administered with IPD11406 20 mg twice a day. All subjects will undergo screening for 28 days before administration, and those who pass the screening will undergo 28 days of drug administration and observation. Cohort 2 (40 mg, Bid) IPG11406 After cohort 1 complete 28 days of dosing and evaluation, the Safety Monitoring Committee (SMC) will assess the safety and tolerability of IPG11406 based on all accumulated safety data (including follow-up data) and available pharmacokinetic (PK) data. Based on SMC approval, 9\~12 subjects will be orally administered 40 mg with IPD11406 twice a day. All subjects will undergo screening for 28 days before administration, and those who pass the screening will undergo 28 days of drug administration and observation. Cohort 3 (80 mg, Bid) IPG11406 After cohort 2 complete 28 days of dosing and evaluation, the Safety Monitoring Committee (SMC) will assess the safety and tolerability of IPG11406 based on all accumulated safety data (including follow-up data) and available pharmacokinetic (PK) data. Based on SMC approval, 9\~12 subjects will be orally administered 80 mg with IPD11406 twice a day. All subjects will undergo screening for 28 days before administration, and those who pass the screening will undergo 28 days of drug administration and observation.
- Primary Outcome Measures
Name Time Method Evaluate the safety and tolerability via assessment of Adverse events Up to 58 days Grades of AE will be assessed according to CTCAE 5.0
Evaluate the safety and tolerability via Respiration rate of Vital Signs Up to 58 days Changes from baseline， Respiration rate in times per minute
Evaluate the safety and tolerability via Heart rate of Vital Signs Up to 58 days Changes from baseline， Heart rate in beats per minute
Evaluate the safety and tolerability via Blood pressure of Vital Signs Up to 58 days Changes from baseline，Blood pressure in mmHg
Evaluate the safety and tolerability via Body temperature of Vital Signs Up to 58 days Changes from baseline，Body temperature in Celsius degree
Evaluating the safety and tolerability from Red blood cell count of Laboratory Examination Up to 58 days Changes from baseline of Red blood cell count in whole blood is reported in the form of number.
Evaluating the safety and tolerability from White blood cell of Laboratory Examination Up to 58 days Changes from baseline of White blood cell count in whole blood is reported in the form of number.
Evaluating the safety and tolerability from lymphocyte count of Laboratory Examination Up to 58 days Changes from baseline , Lymphocyte count in whole blood is reported in the form of number.
Evaluating the safety and tolerability from hemoglobin of Laboratory Examination Up to 58 days Changes from baseline , Changes of hemoglobin concentration（g/dL）in whole blood will be recorded.
Evaluating the safety and tolerability from Laboratory Examination Up to 58 days Changes from baseline of Laboratory Examination (hematology, clinical chemistry, coagulation, urinalysis)
Evaluating the safety and tolerability from Prothrombin time of Laboratory Examination Up to 58 days Changes from baseline, Prothrombin time (PT) is a screening test for exogenous coagulation factors.
Evaluating the safety and tolerability from Activated partial thromboplastin time of Laboratory Examination Up to 58 days Changes from baseline, Activated partial thromboplastin time (APTT) is a screening test for endogenous coagulation factors.
Evaluating the safety and tolerability from total bilirubin concentration of Laboratory Examination Up to 58 days Changes from baseline, Changes of total bilirubin concentration (μmol/L) in serum will be recorded.
Evaluating the safety and tolerability from direct bilirubin concentratio of Laboratory Examination Up to 58 days Changes from baseline, Changes of direct bilirubin concentration (μmol/L) in serum will be recorded.
Evaluating the safety and tolerability from ALT of Laboratory Examination Up to 58 days Changes from baseline, Changes of ALT concentration (U/L) in serum will be recorded.
Evaluating the safety and tolerability from AST of Laboratory Examination Up to 58 days Changes from baseline, Changes of AST concentration (U/L) in serum will be recorded.
Evaluating the safety and tolerability from creatinine concentration of Laboratory Examination Up to 58 days Changes from baseline, Changes of creatinine concentration (μmol/L) in serum will be recorded.
Evaluating the safety and tolerability from triglyceridesconcentration of Laboratory Examination Up to 58 days Changes from baseline, Changes of triglycerides (TG) concentration (mmol/L) in serum will be recorded.
Evaluating the safety and tolerability from urine protein of Laboratory Examination Up to 58 days Changes from baseline, Changes of urine protein will be examined by qualitative test
Evaluating the safety and tolerability from urine pH value of Laboratory Examination Up to 58 days Changes from baseline, Changes of urine pH value will be recorded.
Evaluating the safety and tolerability from ventricular rate of Electrocardiogram Up to 58 days Changes from Clinical Significant Changes in 12-Lead Electrocardiogram (ECG) findings for ventricular rate (beats/min)
Evaluating the safety and tolerability from PR interval of Electrocardiogram Up to 58 days Changes from Clinical Significant Changes in 12-Lead Electrocardiogram (ECG) findings for PR interval (ms)
Evaluating the safety and tolerability from QRS (ms) of Electrocardiogram Up to 58 days Changes from Clinical Significant Changes in 12-Lead Electrocardiogram (ECG) findings for QRS (ms)
Evaluating the safety and tolerability from QTc of Electrocardiogram Up to 58 days Changes from Clinical Significant Changes in 12-Lead Electrocardiogram (ECG) findings for QTc (ms),
Evaluate the impact of oral IPG11406 on biomarkers in patients with Lupus Nephritis Up to 58 days Changes in biomarkers before and after medication administration in patients
Evaluate the impact of oral administration of IPG11406 on 24-hour urine protein quantitation of proteinuria and renal function in patients with Lupus Nephritis Up to 58 days Measure the changes in 24-hour urine protein quantitation before and after medication administration
Evaluate the impact of oral administration of IPG11406 on estimated glomerular filtration rate of proteinuria and renal function in patients with Lupus Nephritis Up to 58 days Measure the changes in estimated glomerular filtration rate (eGFR) calculated using the MDRD formula before and after medication administration
Evaluate the impact of oral administration of IPG11406 on ratio of 24-hour urine protein to urine creatinine of proteinuria and renal function in patients with Lupus Nephritis Up to 58 days Measure the changes in ratio of 24-hour urine protein to urine creatinine before and after medication administration
Evaluate the impact of oral administration of IPG11406 on proteinuria and renal function in patients with Lupus Nephritis Up to 58 days Measure the changes in 24-hour urine protein quantitation, estimated glomerular filtration rate (eGFR) calculated using the MDRD formula, and the ratio of 24-hour urine protein to urine creatinine before and after medication administration
- Secondary Outcome Measures
Name Time Method Evaluate the preliminary efficacy of oral IPG11406 from Serum ferritin Up to 58 days Changes in Serum ferritin before and after medication administration
Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 in Maximum Plasma Concentration Up to 28 days PK parameters:Maximum Plasma Concentration \[Cmax\]
Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 in Area under the curve Up to 28 days PK parameters (under food effect): Area Under The Curve (AUC)
Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 from clearance at steady state Up to 28 days PK parameters (under food effect): clearance at steady state (CLss/F)
Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 from T1/2 Up to 28 days Elimination half-life (T1/2) after dose
Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 in CL by plasma concentration of whole blood sample Up to 28 days Clearance (CL) after dose
Evaluate the preliminary efficacy of oral IPG11406 from peripheral blood T lymphocyte counts and proportion Up to 58 days Changes in peripheral blood T lymphocyte counts and proportions before and after medication administration
Evaluate the preliminary efficacy of oral IPG11406 from Autoantibodies Up to 58 days Changes in autoantibodies before and after medication administration
Evaluate the preliminary efficacy of oral IPG11406 from Relative count of lymphocyte subsets Up to 58 days Changes in Relative count of lymphocyte subsets before and after medication administration
Evaluate the preliminary efficacy of oral IPG11406 from cytokines Up to 58 days Changes in cytokines before and after medication administration
Evaluate the preliminary efficacy of oral IPG11406 from Th1/Th2 detection Up to 58 days Changes in Th1/Th2 before and after medication administration
Evaluate the preliminary efficacy of oral IPG11406 from Routine immunological tests Up to 58 days Changes in Routine immunological tests before and after medication administration
Evaluate the preliminary efficacy of oral IPG11406 in patients with Lupus Nephritis Up to 58 days Changes in peripheral blood B lymphocyte and T lymphocyte counts and proportions, serum albumin, blood creatinine, blood uric acid, blood urea nitrogen (BUN), white blood cells, blood neutrophils, C-reactive protein, complement C3, complement C4, immunoglobulins (IgG, IgA, IgM, IgE), anti-ds-DNA antibody, anti-nuclear antibody, anti-cardiolipin antibody (A/G/M, IgG, IgM), anti-histone antibody, anti-nucleosome antibody, anti-ribosomal P protein antibody, anti-sm antibody, anti-SSA antibody, IL-6, IL-17, IL-2, IL-1β, IL-10, IFN-α, TNF-α, ferritin, and SLEDAI-2K score before and after medication administration
Evaluate the preliminary efficacy of oral IPG11406 from tests from antiphospholipid antibodies Up to 58 days Changes in tests for antiphospholipid antibodies before and after medication administration
Evaluate the preliminary efficacy of oral IPG11406 from 24-hour urine protein test Up to 58 days Changes in 24-hour urine protein test before and after medication administration
Evaluate the preliminary efficacy of oral IPG11406 from Systemic Lupus Erythematosus Disease Activity Index 2000（SLEDAI-2K） score Up to 58 days Changes in SLEDAI-2K score before and after medication administration。
Minimum and Maximum Values:
The SLEDAI-2K score ranges from 0 (indicating no disease activity) to a maximum possible score that depends on the specific items being scored. However, in practical clinical use, the maximum score is typically much lower than the theoretical maximum, as not all items will be positive in any given patient. The exact maximum score can vary slightly depending on the specific version of the SLEDAI-2K being used, but it is generally well below 100.
In the SLEDAI-2K, higher scores indicate a worse outcome. This is because the scale assigns points based on the presence and severity of various lupus manifestations, such as arthritis, rash, fever, and organ involvement. Therefore, as the score increases, it reflects greater disease activity and potentially more severe disease manifestations.
Trial Locations
- Locations (1)
Nanjing DrumTower Hospital of Nanjing University Medical School
🇨🇳Nanjing, Jiangsu, China