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
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. This study has two parts.In Part A1, there will be 3 dose groups, 20 mg bid (Cohort 1), 40 mg bid (Cohort 2), 80 mg bid (Cohort 3).In Cohorts 1 to 3, there will be 3-6 participants in each cohort.In Part A2, dose expansion will be conducted at the proposed recommended Phase 2 dose (RP2D). All subjects will be screened within 28 days before administration, and eligible subjects will be administered and observed for 28 days after screening. In this part, it is planned to recruit about 36 patients with nephritis. After each cohort has completed the 28-day dosing and evaluation, the safety monitoring committee (SMC) will evaluate the safety and tolerability of IPG11406 based on all accumulated safety data (including follow-up data) and available PK data. Based on the evaluation results of safety and tolerability, the SMC will decide whether to administer the next dose group.Part A1 will determine the recommended Phase 2 dose (RP2D) and maximum tolerated dose (MTD) of IPG11406. The design of Part B will be finalized based on the results of Part A.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Investigational Medical Products: IPG11406 Activity: An antagonist of the GPR183 Dosage form: Tablet Strength: 10 mg and 40 mg Storage:15 \~ 25 °C in a tightly sealed container, protect from light Administration: In each cohort, IPG11406 tablets are orally administered twice a Day with an interval of 12±1 hours. Tablets should not be chewed or crushed.
The First Affiliated Hospital Of Anhui Medical University
Hefei, Anhui, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, China
Evaluate the safety and tolerability via assessment of Adverse events
Grades of AE will be assessed according to CTCAE 5.0
Time frame: Up to 58 days
Evaluate the safety and tolerability via Respiration rate of Vital Signs
Changes from baseline, Respiration rate in times per minute
Time frame: Up to 58 days
Evaluate the safety and tolerability via Heart rate of Vital Signs
Changes from baseline, Heart rate in beats per minute
Time frame: Up to 58 days
Evaluate the safety and tolerability via Blood pressure of Vital Signs
Changes from baseline,Blood pressure in mmHg
Time frame: Up to 58 days
Evaluate the safety and tolerability via Body temperature of Vital Signs
Changes from baseline,Body temperature in Celsius degree
Time frame: Up to 58 days
Evaluating the safety and tolerability from Red blood cell count of Laboratory Examination
Changes from baseline of Red blood cell count in whole blood is reported in the form of number.
Time frame: Up to 58 days
Evaluating the safety and tolerability from White blood cell of Laboratory Examination
Changes from baseline of White blood cell count in whole blood is reported in the form of number.
Time frame: Up to 58 days
Evaluating the safety and tolerability from lymphocyte count of Laboratory Examination
Changes from baseline , Lymphocyte count in whole blood is reported in the form of number.
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Fujian Provincial Hospital
Fuzhou, Fujian, China
Sun Yai-sen Memorial Hospital, Sun Yai-sen University
Guangzhou, Guandong, China
Hebei Petro China Central Hospital
Langfang, Hebei, China
Xinxiang Central Hospital
Xinxiang, Henan, China
Renmin Hospital of Wuhan University
Wuhan, Hubei, China
Wuhan Hospital of Traditional Chinese and Western Medicine
Wuhan, Hubei, China
Xiangya Hospital of Central South University
Changsha, Hunan, China
Nanjing DrumTower Hospital of Nanjing University Medical School
Nanjing, Jiangsu, China
...and 7 more locations
Time frame: Up to 58 days
Evaluating the safety and tolerability from hemoglobin of Laboratory Examination
Changes from baseline , Changes of hemoglobin concentration(g/dL)in whole blood will be recorded.
Time frame: Up to 58 days
Evaluating the safety and tolerability from Laboratory Examination
Changes from baseline of Laboratory Examination (hematology, clinical chemistry, coagulation, urinalysis)
Time frame: Up to 58 days
Evaluating the safety and tolerability from Prothrombin time of Laboratory Examination
Changes from baseline, Prothrombin time (PT) is a screening test for exogenous coagulation factors.
Time frame: Up to 58 days
Evaluating the safety and tolerability from Activated partial thromboplastin time of Laboratory Examination
Changes from baseline, Activated partial thromboplastin time (APTT) is a screening test for endogenous coagulation factors.
Time frame: Up to 58 days
Evaluating the safety and tolerability from total bilirubin concentration of Laboratory Examination
Changes from baseline, Changes of total bilirubin concentration (μmol/L) in serum will be recorded.
Time frame: Up to 58 days
Evaluating the safety and tolerability from direct bilirubin concentratio of Laboratory Examination
Changes from baseline, Changes of direct bilirubin concentration (μmol/L) in serum will be recorded.
Time frame: Up to 58 days
Evaluating the safety and tolerability from ALT of Laboratory Examination
Changes from baseline, Changes of ALT concentration (U/L) in serum will be recorded.
Time frame: Up to 58 days
Evaluating the safety and tolerability from AST of Laboratory Examination
Changes from baseline, Changes of AST concentration (U/L) in serum will be recorded.
Time frame: Up to 58 days
Evaluating the safety and tolerability from creatinine concentration of Laboratory Examination
Changes from baseline, Changes of creatinine concentration (μmol/L) in serum will be recorded.
Time frame: Up to 58 days
Evaluating the safety and tolerability from triglyceridesconcentration of Laboratory Examination
Changes from baseline, Changes of triglycerides (TG) concentration (mmol/L) in serum will be recorded.
Time frame: Up to 58 days
Evaluating the safety and tolerability from urine protein of Laboratory Examination
Changes from baseline, Changes of urine protein will be examined by qualitative test
Time frame: Up to 58 days
Evaluating the safety and tolerability from urine pH value of Laboratory Examination
Changes from baseline, Changes of urine pH value will be recorded.
Time frame: Up to 58 days
Evaluating the safety and tolerability from ventricular rate of Electrocardiogram
Changes from Clinical Significant Changes in 12-Lead Electrocardiogram (ECG) findings for ventricular rate (beats/min)
Time frame: Up to 58 days
Evaluating the safety and tolerability from PR interval of Electrocardiogram
Changes from Clinical Significant Changes in 12-Lead Electrocardiogram (ECG) findings for PR interval (ms)
Time frame: Up to 58 days
Evaluating the safety and tolerability from QRS (ms) of Electrocardiogram
Changes from Clinical Significant Changes in 12-Lead Electrocardiogram (ECG) findings for QRS (ms)
Time frame: Up to 58 days
Evaluating the safety and tolerability from QTc of Electrocardiogram
Changes from Clinical Significant Changes in 12-Lead Electrocardiogram (ECG) findings for QTc (ms),
Time frame: Up to 58 days
Evaluate the impact of oral IPG11406 on biomarkers in patients with Lupus Nephritis
Changes in biomarkers before and after medication administration in patients
Time frame: Up to 58 days
Evaluate the impact of oral administration of IPG11406 on 24-hour urine protein quantitation of proteinuria and renal function in patients with Lupus Nephritis
Measure the changes in 24-hour urine protein quantitation before and after medication administration
Time frame: Up to 58 days
Evaluate the impact of oral administration of IPG11406 on estimated glomerular filtration rate of proteinuria and renal function in patients with Lupus Nephritis
Measure the changes in estimated glomerular filtration rate (eGFR) calculated using the MDRD formula before and after medication administration
Time frame: Up to 58 days
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
Measure the changes in ratio of 24-hour urine protein to urine creatinine before and after medication administration
Time frame: Up to 58 days
Evaluate the impact of oral administration of IPG11406 on proteinuria and renal function in patients with Lupus Nephritis
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
Time frame: Up to 58 days
Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 in Maximum Plasma Concentration
PK parameters:Maximum Plasma Concentration \[Cmax\]
Time frame: Up to 28 days
Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 in Area under the curve
PK parameters (under food effect): Area Under The Curve (AUC)
Time frame: Up to 28 days
Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 from clearance at steady state
PK parameters (under food effect): clearance at steady state (CLss/F)
Time frame: Up to 28 days
Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 from T1/2
Elimination half-life (T1/2) after dose
Time frame: Up to 28 days
Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 in CL by plasma concentration of whole blood sample
Clearance (CL) after dose
Time frame: Up to 28 days
Evaluate the preliminary efficacy of oral IPG11406 from peripheral blood T lymphocyte counts and proportion
Changes in peripheral blood T lymphocyte counts and proportions before and after medication administration
Time frame: Up to 58 days
Evaluate the preliminary efficacy of oral IPG11406 from Autoantibodies
Changes in autoantibodies before and after medication administration
Time frame: Up to 58 days
Evaluate the preliminary efficacy of oral IPG11406 from Relative count of lymphocyte subsets
Changes in Relative count of lymphocyte subsets before and after medication administration
Time frame: Up to 58 days
Evaluate the preliminary efficacy of oral IPG11406 from cytokines
Changes in cytokines before and after medication administration
Time frame: Up to 58 days
Evaluate the preliminary efficacy of oral IPG11406 from Th1/Th2 detection
Changes in Th1/Th2 before and after medication administration
Time frame: Up to 58 days
Evaluate the preliminary efficacy of oral IPG11406 from Routine immunological tests
Changes in Routine immunological tests before and after medication administration
Time frame: Up to 58 days
Evaluate the preliminary efficacy of oral IPG11406 in patients with Lupus Nephritis
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
Time frame: Up to 58 days
Evaluate the preliminary efficacy of oral IPG11406 from 24-hour urine protein test
Changes in 24-hour urine protein test before and after medication administration
Time frame: Up to 58 days
Evaluate the preliminary efficacy of oral IPG11406 from Serum ferritin
Changes in Serum ferritin before and after medication administration
Time frame: Up to 58 days
Evaluate the preliminary efficacy of oral IPG11406 from Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K) score
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.
Time frame: Up to 58 days