Phase 1b/2a Study to Evaluate Safety and Efficacy of KPG-818 in SLE
- Conditions
- SLE; Drug
- Interventions
- Drug: KPG-818 mid doseDrug: KPG-818 low doseDrug: KPG-818 high doseDrug: Placebo
- Registration Number
- NCT04643067
- Lead Sponsor
- Kangpu Biopharmaceuticals, Ltd.
- Brief Summary
Study Title
A phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to assess the safety and tolerability, pharmacokinetics and preliminary efficacy of KPG-818 in patients with mild to moderate systemic lupus erythematosus
- Detailed Description
This is a Phase 1b/2a multicenter study to evaluate the safety, PK, PD, and clinical efficacy of KPG-818 in patients with SLE. The trial will consist of 2 parts: Phase 1b, a multiple-ascending dose (MAD) study; and Phase 2a, a proof of concept (POC) study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description KPG-818 mid dose KPG-818 mid dose After providing informed consent, patients will be assessed for study eligibility at the Screening visit. A total of 8 to 12 patients will be randomized to receive this dose level of KPG-818 in a double-blind fashion. Patients will receive treatment for 12 weeks with a 4-week safety follow-up. Capsules of this level of dosage will be taken orally in the morning once a day. All patients will return for follow-up visits after their final dose. The total duration of study participation for each patient (from Screening through Follow-up visit) is anticipated to be approximately 20 weeks. KPG-818 low dose KPG-818 low dose After providing informed consent, patients will be assessed for study eligibility at the Screening visit. A total of 8 to 12 patients will be randomized to receive this dose level of KPG-818 in a double-blind fashion. Patients will receive treatment for 12 weeks with a 4-week safety follow-up. Capsules of this level of dosage will be taken orally in the morning once a day. All patients will return for follow-up visits after their final dose. The total duration of study participation for each patient (from Screening through Follow-up visit) is anticipated to be approximately 20 weeks. KPG-818 high dose KPG-818 high dose After providing informed consent, patients will be assessed for study eligibility at the Screening visit. A total of 8 to 12 patients will be randomized to receive this dose level of KPG-818 in a double-blind fashion. Patients will receive treatment for 12 weeks with a 4-week safety follow-up. Capsules of this level of dosage will be taken orally in the morning once a day. All patients will return for follow-up visits after their final dose. The total duration of study participation for each patient (from Screening through Follow-up visit) is anticipated to be approximately 20 weeks. Placebo arm Placebo After providing informed consent, patients will be assessed for study eligibility at the Screening visit. A total of 8 to 12 patients will be randomized to receive this dose level of KPG-818 in a double-blind fashion. Patients will receive treatment for 12 weeks with a 4-week safety follow-up. Capsules of this level of dosage will be taken orally in the morning once a day. All patients will return for follow-up visits after their final dose. The total duration of study participation for each patient (from Screening through Follow-up visit) is anticipated to be approximately 20 weeks.
- Primary Outcome Measures
Name Time Method Safety assessment by out of normal range of ECG results 4 weeks for phase Ib and 16 weeks for phase IIa To calculate the occurrence rate of out of normal range of ECG results.
PK profile of time to peak (Tmax) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured on Day 1 after dose administration and after the plasma concentration reaches a steady state.
PK profile of the mean retention time (MRT) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured after the plasma concentration reaches a steady state.
PK profile of the cumulative coefficient (R) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured after the plasma concentration reaches a steady state.
Safety assessment by the changes from baseline in laboratory parameters 4 weeks for phase Ib and 16 weeks for phase IIa To calculate the occurrence rate of out of normal ranges of laboratory parameter changes from baseline.
PK profile of trough concentrations at steady state (Css_min) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured after the plasma concentration reaches a steady state.
PK profile of peak plasma concentration (Cmax) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured on Day 1 after dose administration.
PK profile of the clearance (CL/F) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured after the plasma concentration reaches a steady state.
Assess the proportion of patients with improvement of clinical scores of SELENA-SLEDAI (safety of estrogens in lupus national assessment-systemic lupus erythematosus disease activity index) improvement ≥ 4 points from baseline at Week 12. 16 weeks for phase IIa To calculate the proportion of patients with SELENA-SLEDAI (safety of estrogens in lupus national assessment-systemic lupus erythematosus disease activity index) improvement ≥ 4 points from baseline at Week 12. Note: the SELENA-SLEDAI scale ranges from 0\~105, with 105 as the highest disease activity.
Safety assessment by the occurrence of adverse events (AEs) 4 weeks for phase Ib and 16 weeks for phase IIa To calculate the occurrence rate of adverse events (AEs)
Safety assessment by out of normal range of vital signs 4 weeks for phase Ib and 16 weeks for phase IIa To calculate the occurrence rate of out of normal range of vital signs from baseline.
PK profile of elimination half-life (t1/2) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured on Day 1 after dose administration and after the plasma concentration reaches a steady state.
PK profile of the area under the concentration-time curve (AUC0-24h) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured on Day 1 after dose administration.
PK profile of peak concentrations at steady state (Css_max) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured after the plasma concentration reaches a steady state.
PK profile of the area under the concentration-time curve at steady state (AUCτ, AUC0-∞) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured after the plasma concentration reaches a steady state.
PK profile of the apparent volume of distribution ((Vz/F) for KPG-818 and KPG-818H (if applicable). 4 weeks for phase Ib and 16 weeks for phase IIa This will be measured after the plasma concentration reaches a steady state.
- Secondary Outcome Measures
Name Time Method The PK endpoint of Ctrough throughout the dosing period for assessment of KPG-818 and KPG-818H (if applicable) 12 weeks for phase IIa The PK endpoint of Ctrough throughout the dosing period for assessment of KPG-818 and KPG-818H (if applicable)
Number of patients with adverse event at Week 12 12 weeks for phase IIa Number of patients with adverse event at Week 12
Number of patients with adverse event at Week 16. 16 weeks for phase IIa Number of patients with adverse event at Week 16.
The PK endpoint of the measurement of area under the curve (AUC) at Week 12 (AUC0-last) for assessment of KPG-818 and KPG-818H (if applicable). 12 weeks for phase IIa The PK endpoint of the measurement of area under the curve (AUC) at Week 12 (AUC0-last) for assessment of KPG-818 and KPG-818H (if applicable).
The PK endpoint of time to Cmax (tmax) at Week 12 for assessment of KPG-818 and KPG-818H (if applicable) 12 weeks for phase IIa The PK endpoint of time to Cmax (tmax) at Week 12 for assessment of KPG-818 and KPG-818H (if applicable).
The PK endpoint of serum concentrations by scheduled timepoints for assessment of KPG-818 and KPG-818H (if applicable) 12 weeks for phase IIa The PK endpoint of serum concentrations by scheduled timepoints for assessment of KPG-818 and KPG-818H (if applicable)
Mean change from baseline in PGA (Physician Global Assessment) score at Week 12. 16 weeks for phase IIa Mean change from baseline in PGA (Physician Global Assessment) score at Week 12. Note: the PGA is a visual scale for the physician to mark, from 0mm to 100mm, with 0mm being no disease activity and 100mm being the extreme disease activity.
The proportion of patients with a ≥ 50% reduction from baseline in CLASI (Cutaneous Lupus erythematosus disease Area and Severity Index) activity score at Week 12, in patients with baseline CLASI activity score ≥ 10. 16 weeks for phase IIa The proportion of patients with a ≥ 50% reduction from baseline in CLASI (Cutaneous Lupus erythematosus disease Area and Severity Index) activity score at Week 12, in patients with baseline CLASI activity score ≥ 10. Note: the total CLASI score ranges from 0 to 114, with 0 being the least disease activity and 114 being the most.
The PK endpoint of the maximum observed concentration (Cmax) at Week 12 for assessment of KPG-818 and KPG-818H (if applicable) 12 weeks for phase IIa The PK endpoint of the maximum observed concentration (Cmax) at Week 12 for assessment of KPG-818 and KPG-818H (if applicable)
Trial Locations
- Locations (18)
Anniston Medical Clinic
🇺🇸Anniston, Alabama, United States
Hope Clinical Trials, Inc.
🇺🇸Coral Gables, Florida, United States
STAT Research
🇺🇸Vandalia, Ohio, United States
JY Research Institute Inc
🇺🇸Cutler Bay, Florida, United States
Oracle Clinical Research
🇺🇸College Park, Georgia, United States
Clinical Research of West Florida, Inc.
🇺🇸Clearwater, Florida, United States
OSIS Clinical Research
🇺🇸Hollywood, Florida, United States
Charisma Medical and Research Center
🇺🇸Miami Lakes, Florida, United States
San Marcus Research Clinic
🇺🇸Miami Lakes, Florida, United States
Accurate Clinical Management
🇺🇸Houston, Texas, United States
Accurate Clinical Research LLC
🇺🇸Houston, Texas, United States
SouthCoast Research Center Inc
🇺🇸Miami, Florida, United States
D & H National Research Centers
🇺🇸Miami, Florida, United States
Shelby Research LLC
🇺🇸Memphis, Tennessee, United States
University of Alabama - Birmingham
🇺🇸Birmingham, Alabama, United States
Sun Research Institute
🇺🇸San Antonio, Texas, United States
Clinical Research of West Florida
🇺🇸Tampa, Florida, United States
Omega Research MetroWest LLC
🇺🇸Orlando, Florida, United States