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
概览
- 阶段
- 1 期
- 干预措施
- IPG11406
- 疾病 / 适应症
- 未指定
- 发起方
- Nanjing Immunophage Biotech Co., Ltd
- 入组人数
- 36
- 试验地点
- 18
- 主要终点
- Evaluate the safety and tolerability via Heart rate of Vital Signs
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
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
详细描述
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.
研究者
入排标准
入选标准
- •Criteria for Inclusion and Exclusion \<Inclusion Criteria\>
- •The age range is between 18 and 70 years old (including 18 and 70), with no gender restrictions.
- •Weight ≥ 45kg.
- •Adult subjects who meet the revised classification criteria of the American College of Rheumatology (ACR) 1997 and were diagnosed with systemic lupus erythematosus before screening.
- •During the screening period, the disease activity was confirmed as follows: SLEDAI-2K score ≥ 6 points. Accompanied by lupus nephritis (according to the 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification criteria, there is active, biopsy-confirmed type III or type IV proliferative lupus nephritis, with coexistence of type V allowed; the biopsy must be performed within 1 year before the screening visit or during the screening period, and the biopsy report is used to confirm patient eligibility.)
- •During the screening period, the patient's 24-hour urinary protein to creatinine ratio (UPCR) is greater than 1.0g/g, and the estimated glomerular filtration rate (eGFR) calculated using the MDRD formula is ≥60 mL/min/1.73 m\^2; and the 24-hour urinary protein is ≥1g.
- •The patient's baseline serum IFN-γ exceeded the upper limit of normal values.
- •The Th1/Th2 ratio in peripheral blood of the patient during the baseline period is ≥
- •Subjects who have not undergone induction therapy are allowed to be enrolled, but during the study and follow-up period, they must not receive any other treatment for systemic lupus erythematosus and lupus nephritis. Subjects are allowed to be enrolled while receiving any of the following standard treatment regimens: 1) Oral prednisone (or equivalent) monotherapy: a. Treatment duration: medication use ≥2 weeks before screening and maintaining a stable dose ≥2 weeks before enrollment; b. Dose requirements: maximum daily dose: 1mg/kg/day; 2) Immunosuppressants: a. Permissible drugs include: antimalarials, azathioprine, cyclophosphamide, mycophenolate mofetil/mycophenolic acid, methotrexate, cyclosporine A, tacrolimus; b. Treatment duration: medication use ≥12 weeks before screening and maintaining a stable dose ≥8 weeks before enrollment; c. Dose requirements: hydroxychloroquine ≤400mg/day, azathioprine ≤100mg/day, cyclophosphamide ≤800mg/4 weeks, mycophenolate mofetil/mycophenolic acid ≤2g/day, oral, subcutaneous (SC), or intramuscular methotrexate ≤15mg/week, Cyclosporine A ≤ 3 mg/kg/d, tacrolimus ≤ 3 mg/d; 3) Oral prednisone (or equivalent medication) monotherapy ± hydroxychloroquine sulfate ± an immunosuppressant: a. The treatment duration and dose stability requirements for Oral glucocorticoids (OCS) and immunosuppressants mentioned above must be met; b. The maximum daily/weekly dose of each drug in 1) and 2) must not be exceeded.
- •Female subjects must be in a non-pregnant and non-breastfeeding period during the trial.
排除标准
- •Pregnant and lactating women.
- •Screening for participation in other clinical trials within the previous 3 months and/or currently (excluding those who have not used the trial medication).
- •Active severe lupus nephritis, with estimated glomerular filtration rate (eGFR) calculated using the MDRD formula \<60ml/min/1.73m\^
- •Severe neuropsychiatric SLE includes but is not limited to the following: seizures, new or worsening impaired level of consciousness, psychosis, delirium or confusion state, aseptic meningitis, ascending or transverse myelitis, chorea, cerebellar ataxia, multiple mononeuropathy, demyelinating syndrome, or situations that make the subject unable to fully understand the ICF.
- •History or current diagnosis of clinically significant non-SLE-related vasculitis syndrome or overlap with other connective tissue diseases.
- •Any active skin diseases that may interfere with the research evaluation of SLE, including but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-SLE skin lupus manifestations (such as skin vascular disease, perifollicular telangiectasia, fingertip sclerosis, rheumatoid nodules, erythema multiforme, leg ulcers) or drug-induced lupus, except for SLE.
- •Those with a history of lymphoproliferative diseases, or those who have had or currently have malignant tumors within the past 5 years (except for squamous cell carcinoma in situ, basal cell carcinoma, and cervical carcinoma in situ, which have been thoroughly treated and show no evidence of recurrence).
- •Patients with uncontrolled antiphospholipid syndrome (APS).
- •History of significant organ transplantation (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation.
- •Major surgical procedures (craniotomy, thoracotomy, or abdominal surgery) or unhealed wounds, ulcers, or fractures within 4 weeks before screening.
研究组 & 干预措施
Cohort 1 (20 mg, Bid)
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.
干预措施: IPG11406
Cohort 2 (40 mg, Bid)
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.
干预措施: IPG11406
Cohort 3 (80 mg, Bid)
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.
干预措施: IPG11406
结局指标
主要结局
Evaluate the safety and tolerability via Heart rate of Vital Signs
时间窗: Up to 58 days
Changes from baseline， Heart rate in beats per minute
Evaluate the safety and tolerability via Blood pressure of Vital Signs
时间窗: Up to 58 days
Changes from baseline，Blood pressure in mmHg
Evaluating the safety and tolerability from Red blood cell count of Laboratory Examination
时间窗: 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 ALT of Laboratory Examination
时间窗: Up to 58 days
Changes from baseline, Changes of ALT concentration (U/L) in serum will be recorded.
Evaluate the impact of oral administration of IPG11406 on 24-hour urine protein quantitation of proteinuria and renal function in patients with Lupus Nephritis
时间窗: Up to 58 days
Measure the changes in 24-hour urine protein quantitation before and after medication administration
Evaluate the safety and tolerability via assessment of Adverse events
时间窗: Up to 58 days
Grades of AE will be assessed according to CTCAE 5.0
Evaluating the safety and tolerability from Laboratory Examination
时间窗: Up to 58 days
Changes from baseline of Laboratory Examination (hematology, clinical chemistry, coagulation, urinalysis)
Evaluate the safety and tolerability via Respiration rate of Vital Signs
时间窗: Up to 58 days
Changes from baseline， Respiration rate in times per minute
Evaluating the safety and tolerability from Prothrombin time of Laboratory Examination
时间窗: Up to 58 days
Changes from baseline, Prothrombin time (PT) is a screening test for exogenous coagulation factors.
Evaluating the safety and tolerability from AST of Laboratory Examination
时间窗: Up to 58 days
Changes from baseline, Changes of AST concentration (U/L) in serum will be recorded.
Evaluate the safety and tolerability via Body temperature of Vital Signs
时间窗: Up to 58 days
Changes from baseline，Body temperature in Celsius degree
Evaluating the safety and tolerability from White blood cell of Laboratory Examination
时间窗: 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
时间窗: 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 total bilirubin concentration of Laboratory Examination
时间窗: 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 hemoglobin of Laboratory Examination
时间窗: 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 Activated partial thromboplastin time of Laboratory Examination
时间窗: 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 direct bilirubin concentratio of Laboratory Examination
时间窗: 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 creatinine concentration of Laboratory Examination
时间窗: 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
时间窗: 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 QRS (ms) of Electrocardiogram
时间窗: Up to 58 days
Changes from Clinical Significant Changes in 12-Lead Electrocardiogram (ECG) findings for QRS (ms)
Evaluating the safety and tolerability from urine protein of Laboratory Examination
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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 QTc of Electrocardiogram
时间窗: 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
时间窗: Up to 58 days
Changes in biomarkers before and after medication administration in patients
Evaluate the impact of oral administration of IPG11406 on estimated glomerular filtration rate of proteinuria and renal function in patients with Lupus Nephritis
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 in CL by plasma concentration of whole blood sample(Up to 28 days)
- Evaluate the preliminary efficacy of oral IPG11406 from Relative count of lymphocyte subsets(Up to 58 days)
- Evaluate the preliminary efficacy of oral IPG11406 from Routine immunological tests(Up to 58 days)
- Evaluate the preliminary efficacy of oral IPG11406 from tests from antiphospholipid antibodies(Up to 58 days)
- Evaluate the preliminary efficacy of oral IPG11406 from Serum ferritin(Up to 58 days)
- Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 in Area under the curve(Up to 28 days)
- Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 in Maximum Plasma Concentration(Up to 28 days)
- Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 from T1/2(Up to 28 days)
- Evaluate the pharmacokinetics (PK) characteristics of oral IPG11406 from clearance at steady state(Up to 28 days)
- Evaluate the preliminary efficacy of oral IPG11406 from cytokines(Up to 58 days)
- Evaluate the preliminary efficacy of oral IPG11406 from peripheral blood T lymphocyte counts and proportion(Up to 58 days)
- Evaluate the preliminary efficacy of oral IPG11406 from Autoantibodies(Up to 58 days)
- Evaluate the preliminary efficacy of oral IPG11406 from Th1/Th2 detection(Up to 58 days)
- Evaluate the preliminary efficacy of oral IPG11406 in patients with Lupus Nephritis(Up to 58 days)
- Evaluate the preliminary efficacy of oral IPG11406 from 24-hour urine protein test(Up to 58 days)
- Evaluate the preliminary efficacy of oral IPG11406 from Systemic Lupus Erythematosus Disease Activity Index 2000（SLEDAI-2K） score(Up to 58 days)