A Study in Participants With Mild-to-moderate Systemic Lupus Erythematosus

A Phase Ib, Randomized, Double-Blind, Placebo-Controlled, Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered CUG252 Following Multiple Dose Administrations in Participants With Mild-to-Moderate SLE

The main purpose of this study is to evaluate the safety and tolerability of CUG252 following multiple ascending doses in participants with Systemic Lupus Erythematosus (SLE).

Study Overview

• Status: Active, not recruiting
• Conditions: Systemic Lupus Erythematosus; Autoimmune; SLE (Systemic Lupus)
• Intervention / Treatment: Drug: CUG252; Drug: Placebo

Detailed Description

CUG252 is a potential best-in-class engineered IL-2 compound, designed to have improved Treg selectivity while reducing undesired IL-2 activity.

This study will evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunologic effects of CUG252 following subcutaneous administration of multiple ascending doses in participants with mild-to-moderate SLE. The effects of SLE disease activity and biomarkers will also be evaluated.. The SLE participants will receive randomized multiple subcutaneous doses of CUG252 or placebo. After receiving the last dose of CUG252 or placebo, participants will be followed to study day 64 post first dose administration to evaluate safety, PK, PD and preliminary efficacy.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Site 1001
  • California
    • La Jolla, California, United States, 92037
      • Site 1011
  • Florida
    • Clearwater, Florida, United States, 33765
      • Site 1002
    • Tampa, Florida, United States, 33606
      • Site 1009
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Site 1007
  • Ohio
    • Columbus, Ohio, United States, 44106
      • Site 1010
    • Middleburg Heights, Ohio, United States, 44130
      • Site 1005
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Site 1003
  • Texas
    • Dallas, Texas, United States, 75231
      • Site 1006
    • Mesquite, Texas, United States, 75150
      • Site 1004
  • Washington
    • Seattle, Washington, United States, 98195
      • Site 1012

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female participant, aged 18 to 65 years (inclusive), at time of consent
• BMI greater than or equal to 18 and less than 39 kg/m2 at Screening
• Diagnosis of SLE at least 6 months prior to Screening
• Minimal to moderate SLE disease activity
• If a participant is taking oral prednisone, the dose must be less than or equal to 20 mg/day for a minimum of 8 weeks prior to Screening and at a stable dose for a minimum of 2 weeks prior to Screening
• If a participant is taking azathioprine, antimalarial, mycophenolate mofetil, or methotrexate, the medication(s) must have been started a minimum of 12 weeks prior to Screening and at a stable dose for a minimum of 8 weeks prior to Screening

Exclusion Criteria:

• Have one or more of the following medical conditions: SARS-CoV-2 infection 30 days prior to drug administration, evidence of Grade 3 or greater hematologic, hepatic, or rental dysfunction, active severe or unstable neuropsychiatric SLE, active severe renal disease, history of severe active lupus nephritis with proteinuria levels greater than 1.0 g/24 hours, or dialysis in the last 6 months. History of current diagnosis of other autoimmune/inflammatory diseases, history of any non-SLE disease that has required treatment with corticosteroids for more than 2 weeks within the last 12 weeks prior to Screening, active clinically significant bacterial, viral, or fungal infection at Screening, active or latent TB at Screening, pulmonary infection or active lung disease besides those related to lupus, or severe pulmonary disease requiring oxygen therapy. History of condition that predisposes participant to infection, confirmed positive serology at Screening, history of opportunistic infection requiring hospitalization or IV antimicrobial treatment within the last year, history of organ or hematopoietic stem cell transplant, history of major surgery within 12 weeks of Screening, history of significant cardiovascular disease, history of gastrointestinal bleeding, history of cancer apart from successfully treated squamous or basal cell carcinoma or cervical cancer in situ.
• Are on one or more of the following medications: have received vaccination within 30 days prior to Screening (including COVID-19 vaccination), Aldesleukin or other IL-2 derivatives at any time, T cell depleting agents and inhibitors of T cell activation at any time, Anti-BLyS/BAFF inhibitors, IL-1 receptor antagonist, anti-TNF therapy, and anti-interferon alpha receptor inhibitor within 3 months prior to Screening, rituximab or other B-cell depleting agent within 6 months, glucocorticoids within 6 weeks prior to Day 1, other immunosuppressant drugs within 8 weeks, history of cytotoxic medications within 12 months, receipt of blood products within 6 months, plasmapheresis within 30 days of Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CUG252; CUG252 or placebo will be administered to participants in a 3:1 ratio.	Drug: CUG252; CUG252 will be administered by subcutaneous injection.
Placebo Comparator: Placebo; CUG252 or placebo will be administered to participants in a 3:1 ratio.	Drug: Placebo; Placebo will be administered by subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and percentage of subjects with Treatment Emergent Adverse Events	To evaluate the safety and tolerability of multiple ascending doses (MAD) in participants with mild to moderate SLE.	Up to 64 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics profile of CUG252 (AUC)	To assess the Area under the plasma concentration versus time curve (AUC)	Day 1 pre dose through Day 64
Pharmacokinetics profile of CUG252 (Cmax)	To assess the maximum plasma concentration (Cmax)	Day 1 pre dose through Day 64
Pharmacokinetics profile of CUG252 (Tmax)	To assess the time of maximum concentration (Tmax)	Day 1 pre dose through Day 64
Pharmacokinetics profile of CUG252 (t1/2)	To assess the half-life (t1/2)	Day 1 pre dose through Day 64
Immunogenicity of CUG252	To measure the serum concentration of antibodies against CUG252	Day 1 pre dose through Day 64
Change in the number and percentages of immune cells	To assess the effect of CUG252 on immuno-pharmacodynamic endpoints.	Day 1 pre dose through Day 64

Collaborators and Investigators

• Sponsor: Cugene Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 18, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: CUG252-P102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No