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

NCT04643067 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: KPG-818-SLE
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 18

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

Conditions

SLE; Drug

Outcome Measures

Primary Outcomes (16)

• Safety assessment by the occurrence of adverse events (AEs)

  To calculate the occurrence rate of adverse events (AEs)

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  16 weeks for phase IIa

Secondary Outcomes (9)

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

  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.

  16 weeks for phase IIa

• Number of patients with adverse event at Week 12

  12 weeks for phase IIa

• Number of patients with adverse event at Week 16.

  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).

  12 weeks for phase IIa

Other Outcomes (9)

• Explore the mean change from baseline in potential biomarker, i.e. Aiolos, of KPG-818 in PBMCs and CD19+ B Cells at Week 2.

  2 weeks for phase Ib

• Explore the mean change from baseline in potential biomarker, i.e. Ikaros, of KPG-818 in PBMCs and CD19+ B Cells at Week 2.

  2 weeks for phase Ib

• 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.

  2 weeks for phase Ib

Study Arms (4)

KPG-818 low dose

ACTIVE COMPARATOR

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.

Drug: KPG-818 low dose

KPG-818 mid dose

ACTIVE COMPARATOR

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.

Drug: KPG-818 mid dose

KPG-818 high dose

ACTIVE COMPARATOR

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.

Drug: KPG-818 high dose

Placebo arm

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

KPG-818 low dose DRUG

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 low dose

KPG-818 mid dose DRUG

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 dose

KPG-818 high dose DRUG

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 dose

Placebo DRUG

This is the comparative arm.

Placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age≥18
• BMI between 18-40kg/m²
• Diagnosed with SLE according to the 2019 EULAR/ACR criteria for SLE
• Meeting SLE activity requirements
• Males and females childbearing potential must agree to use contraception methods
• All patients must:
• Understand that KPG-818 could have potential teratogenic risk.
• Agree not to share KPG-818 with another person.
• Be counseled about pregnancy precautions and risks of fetal exposure as described in the Pregnancy Prevention Plan.
• 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.
• Patients must be willing to comply with precautions to reduce the risk of COVID-19 infection and to undergo COVID-19 PCR test.

You may not qualify if:

• Use of any prohibited medications within the pre-specified time
• Active and/or unstable neuropsychiatric SLE
• Active or history of severe systemic bacterial, viral, fungal, mycobacterial, or parasitic infections within 6 months prior to Screening
• Current or recent sign or symptoms of infections, or severe viral infections
• Conditions predisposes patient to infection
• Active TB or positive QuantiFERON®-TB Gold test
• Patients with malignancy and antiphospholipid syndrome history
• Inflammatory joint or skin disease, mixed connective tissue disease, scleroderma, and/or overlap syndromes, or acute or chronic disease
• Concomitant condition that required systemic corticosteroid use within 1 year before Screening
• Alcohol or drug abuse history
• Positive urine drug test at screening
• History or planned major surgery
• Pregnant or breastfeeding female
• Signs or symptoms of COVID-19 infection
• Known allergic reaction to any of the ingredients for study drug or placebo

Sponsors & Collaborators

• Kangpu Biopharmaceuticals, Ltd.: lead

Study Sites (18)

Anniston Medical Clinic

Anniston, Alabama, 36207, United States

Location

University of Alabama - Birmingham

Birmingham, Alabama, 35205, United States

Location

Clinical Research of West Florida, Inc.

Clearwater, Florida, 33765, United States

Location

Hope Clinical Trials, Inc.

Coral Gables, Florida, 33134, United States

Location

JY Research Institute Inc

Cutler Bay, Florida, 33189, United States

Location

OSIS Clinical Research

Hollywood, Florida, 33020, United States

Location

SouthCoast Research Center Inc

Miami, Florida, 33136, United States

Location

D & H National Research Centers

Miami, Florida, 33155, United States

Location

Charisma Medical and Research Center

Miami Lakes, Florida, 33014, United States

Location

San Marcus Research Clinic

Miami Lakes, Florida, 33014, United States

Location

Omega Research MetroWest LLC

Orlando, Florida, 32808, United States

Location

Clinical Research of West Florida

Tampa, Florida, 33606, United States

Location

Oracle Clinical Research

College Park, Georgia, 30329, United States

Location

STAT Research

Vandalia, Ohio, 54377, United States

Location

Shelby Research LLC

Memphis, Tennessee, 38119, United States

Location

Accurate Clinical Management

Houston, Texas, 77084, United States

Location

Accurate Clinical Research LLC

Houston, Texas, 77089, United States

Location

Sun Research Institute

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Conditions

drug-induced lupus

Study Officials

• MD

  Kangpu Biopharmaceuticals, Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: November 24, 2020
• Study Start: June 3, 2021
• Primary Completion: August 18, 2023
• Study Completion: August 18, 2023
• Last Updated: May 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)