Clinical trial NCT04643067: Phase 1b/2a Study to Evaluate Safety and Efficacy of KPG-818 in SLE
Official title: A Phase 1b/2a Multicenter Study to Assess the Safety and Tolerability, Pharmacokinetics, and Preliminary Efficacy of KPG-818 in Patients With Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: SLE; Drug
Lead sponsor: Kangpu Biopharmaceuticals, Ltd.
Sponsor class: INDUSTRY
First posted: 2020-11-24
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety assessment by the occurrence of adverse events (AEs)
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: Safety assessment by the changes from baseline in laboratory parameters
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: Safety assessment by out of normal range of vital signs
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: Safety assessment by out of normal range of ECG results
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of time to peak (Tmax) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of peak plasma concentration (Cmax) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of elimination half-life (t1/2) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of the area under the concentration-time curve (AUC0-24h) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of the mean retention time (MRT) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of trough concentrations at steady state (Css_min) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of peak concentrations at steady state (Css_max) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of the area under the concentration-time curve at steady state (AUCτ, AUC0-∞) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of the clearance (CL/F) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of the apparent volume of distribution ((Vz/F) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: PK profile of the cumulative coefficient (R) for KPG-818 and KPG-818H (if applicable).
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
measure: 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.
timeFrame: 16 weeks for phase IIa
Secondary outcomes:
measure: Mean change from baseline in PGA (Physician Global Assessment) score at Week 12.
timeFrame: 16 weeks for phase IIa
measure: 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.
timeFrame: 16 weeks for phase IIa
measure: Number of patients with adverse event at Week 12
timeFrame: 12 weeks for phase IIa
measure: Number of patients with adverse event at Week 16.
timeFrame: 16 weeks for phase IIa
measure: 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).
timeFrame: 12 weeks for phase IIa
measure: The PK endpoint of the maximum observed concentration (Cmax) at Week 12 for assessment of KPG-818 and KPG-818H (if applicable)
timeFrame: 12 weeks for phase IIa
measure: The PK endpoint of time to Cmax (tmax) at Week 12 for assessment of KPG-818 and KPG-818H (if applicable)
timeFrame: 12 weeks for phase IIa
measure: The PK endpoint of Ctrough throughout the dosing period for assessment of KPG-818 and KPG-818H (if applicable)
timeFrame: 12 weeks for phase IIa
measure: The PK endpoint of serum concentrations by scheduled timepoints for assessment of KPG-818 and KPG-818H (if applicable)
timeFrame: 12 weeks for phase IIa
Other outcomes:
measure: Explore the mean change from baseline in potential biomarker, i.e. Aiolos, of KPG-818 in PBMCs and CD19+ B Cells at Week 2.
timeFrame: 2 weeks for phase Ib
measure: Explore the mean change from baseline in potential biomarker, i.e. Ikaros, of KPG-818 in PBMCs and CD19+ B Cells at Week 2.
timeFrame: 2 weeks for phase Ib
measure: Explore the mean change from baseline in potential biomarker, i.e. CRBN proteins, of KPG-818 in PBMCs and CD19+ B Cells at Week 2.
timeFrame: 2 weeks for phase Ib
measure: Mean change from baseline in potential biomarker, i.e. CRBN proteins, of KPG-818 in PBMCs and CD19+ B cells at week 12
timeFrame: 12 weeks for phase IIa
measure: Mean change from baseline in potential biomarker, i.e. Aiolos, of KPG-818 in PBMCs and CD19+ B cells at week 12
timeFrame: 12 weeks for phase IIa
measure: Mean change from baseline in potential biomarker, i.e. Ikaros, of KPG-818 in PBMCs and CD19+ B cells at week 12
timeFrame: 12 weeks for phase IIa
measure: Mean change from baseline in absolute counts of CD 19+ B cell and CD3+ T cell at week 12
timeFrame: 12 weeks for phase IIa
measure: Mean change from baseline in IgA, IgG and IgM in serum at week 12
timeFrame: 12 weeks for phase IIa
measure: Dose regimens for a Phase 2b/phase 3 study
timeFrame: 4 weeks for phase Ib and 16 weeks for phase IIa
Locations:
city: Anniston
country: United States
facility: Anniston Medical Clinic
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama - Birmingham
state: Alabama
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Coral Gables
country: United States
facility: Hope Clinical Trials, Inc.
state: Florida
city: Cutler Bay
country: United States
facility: JY Research Institute Inc
state: Florida
city: Hollywood
country: United States
facility: OSIS Clinical Research
state: Florida
city: Miami Lakes
country: United States
facility: Charisma Medical and Research Center
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic
state: Florida
city: Miami
country: United States
facility: SouthCoast Research Center Inc
state: Florida
city: Miami
country: United States
facility: D & H National Research Centers
state: Florida
city: Orlando
country: United States
facility: Omega Research MetroWest LLC
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: College Park
country: United States
facility: Oracle Clinical Research
state: Georgia
city: Vandalia
country: United States
facility: STAT Research
state: Ohio
city: Memphis
country: United States
facility: Shelby Research LLC
state: Tennessee
city: Houston
country: United States
facility: Accurate Clinical Management
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research LLC
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
Study officials:
affiliation: Kangpu Biopharmaceuticals, Ltd.
name: MD
role: STUDY_DIRECTOR
References: