Phase 1b/2a Study to Evaluate Safety and Efficacy of KPG-818 in SLE

Kangpu Biopharmaceuticals, Ltd.64 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

SLE; Drug

Interventions

KPG-818 low doseDRUG

The dose levels may be modified according to the results from phase 1b of the study. Dose adjustment is allowed during the study.

KPG-818 mid doseDRUG

The dose levels may be modified according to the results from phase 1b of the study. Dose adjustment is allowed during the study.

KPG-818 high doseDRUG

The dose levels may be modified according to the results from phase 1b of the study. Dose adjustment is allowed during the study.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria are listed as follows: 1. Age≥18 2. BMI between 18-40kg/m² 3. Diagnosed with SLE according to the 2019 EULAR/ACR criteria for SLE 4. Meeting SLE activity requirements 5. Males and females childbearing potential must agree to use contraception methods 6. All patients must: 1. Understand that KPG-818 could have potential teratogenic risk. 2. Agree not to share KPG-818 with another person. 3. Be counseled about pregnancy precautions and risks of fetal exposure as described in the Pregnancy Prevention Plan. 7. Patients must agree not to donate blood (or any component of blood) from 3 months before Screening until 3 months after the last dose of KPG-818. 8. Patients must be willing to comply with precautions to reduce the risk of COVID-19 infection and to undergo COVID-19 PCR test. Exclusion criteria are listed as follows: 1. Use of any prohibited medications within the pre-specified time 2. Patients must meet exclusionary lab criteria 3. Active and/or unstable neuropsychiatric SLE 4. Active or history of severe systemic bacterial, viral, fungal, mycobacterial, or parasitic infections within 6 months prior to Screening 5. Current or recent sign or symptoms of infections, or severe viral infections 6. Conditions predisposes patient to infection 7. Active TB or positive QuantiFERON®-TB Gold test 8. Patients with malignancy and antiphospholipid syndrome history 9. Inflammatory joint or skin disease, mixed connective tissue disease, scleroderma, and/or overlap syndromes, or acute or chronic disease 10. Concomitant condition that required systemic corticosteroid use within 1 year before Screening 11. Alcohol or drug abuse history 12. Positive urine drug test at screening 13. History or planned major surgery 14. Pregnant or breastfeeding female 15. Signs or symptoms of COVID-19 infection 16. Known allergic reaction to any of the ingredients for study drug or placebo

Locations (18)

Anniston Medical Clinic

Anniston, Alabama, United States

University of Alabama - Birmingham

Birmingham, Alabama, United States

Outcomes

Primary Outcomes

Safety assessment by the occurrence of adverse events (AEs)

To calculate the occurrence rate of adverse events (AEs)

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

Safety assessment by the changes from baseline in laboratory parameters

To calculate the occurrence rate of out of normal ranges of laboratory parameter changes from baseline.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

Safety assessment by out of normal range of vital signs

To calculate the occurrence rate of out of normal range of vital signs from baseline.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

Safety assessment by out of normal range of ECG results

To calculate the occurrence rate of out of normal range of ECG results.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of time to peak (Tmax) for KPG-818 and KPG-818H (if applicable).

This will be measured on Day 1 after dose administration and after the plasma concentration reaches a steady state.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of peak plasma concentration (Cmax) for KPG-818 and KPG-818H (if applicable).

This will be measured on Day 1 after dose administration.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of elimination half-life (t1/2) for KPG-818 and KPG-818H (if applicable).

This will be measured on Day 1 after dose administration and after the plasma concentration reaches a steady state.

Data from ClinicalTrials.gov

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This is the comparative arm.

Clinical Research of West Florida, Inc.

Clearwater, Florida, United States

Hope Clinical Trials, Inc.

Coral Gables, Florida, United States

JY Research Institute Inc

Cutler Bay, Florida, United States

OSIS Clinical Research

Hollywood, Florida, United States

SouthCoast Research Center Inc

Miami, Florida, United States

D & H National Research Centers

Miami, Florida, United States

Charisma Medical and Research Center

Miami Lakes, Florida, United States

San Marcus Research Clinic

Miami Lakes, Florida, United States

...and 8 more locations

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of the area under the concentration-time curve (AUC0-24h) for KPG-818 and KPG-818H (if applicable).

This will be measured on Day 1 after dose administration.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of the mean retention time (MRT) for KPG-818 and KPG-818H (if applicable).

This will be measured after the plasma concentration reaches a steady state.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of trough concentrations at steady state (Css_min) for KPG-818 and KPG-818H (if applicable).

This will be measured after the plasma concentration reaches a steady state.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of peak concentrations at steady state (Css_max) for KPG-818 and KPG-818H (if applicable).

This will be measured after the plasma concentration reaches a steady state.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of the area under the concentration-time curve at steady state (AUCτ, AUC0-∞) for KPG-818 and KPG-818H (if applicable).

This will be measured after the plasma concentration reaches a steady state.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of the clearance (CL/F) for KPG-818 and KPG-818H (if applicable).

This will be measured after the plasma concentration reaches a steady state.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of the apparent volume of distribution ((Vz/F) for KPG-818 and KPG-818H (if applicable).

This will be measured after the plasma concentration reaches a steady state.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

PK profile of the cumulative coefficient (R) for KPG-818 and KPG-818H (if applicable).

This will be measured after the plasma concentration reaches a steady state.

Time frame: 4 weeks for phase Ib and 16 weeks for phase IIa

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.

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.

Time frame: 16 weeks for phase IIa

Secondary Outcomes

Mean change from baseline in PGA (Physician Global Assessment) score at Week 12.

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.

Time frame: 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.

Time frame: 16 weeks for phase IIa

Number of patients with adverse event at Week 12

Time frame: 12 weeks for phase IIa

Number of patients with adverse event at Week 16.

Time frame: 16 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).

Time frame: 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)

Time frame: 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 time to Cmax (tmax) at Week 12 for assessment of KPG-818 and KPG-818H (if applicable).

Time frame: 12 weeks for phase IIa

The PK endpoint of Ctrough throughout the dosing period for assessment of KPG-818 and KPG-818H (if applicable)

Time frame: 12 weeks for phase IIa

The PK endpoint of serum concentrations by scheduled timepoints for assessment of KPG-818 and KPG-818H (if applicable)

Time frame: 12 weeks for phase IIa