UB-VV410 in Subjects With Active Refractory Systemic Lupus Erythematosus or Lupus Nephritis

NCT ID: NCT07109986

Last Updated: 2025-08-07

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-31
• Study Completion Date: 2030-07-08

Brief Summary

This is an open-label investigator-initiated trial (IIT) to assess the safety, efficacy, and PK/PD of UB-VV410 in adult subjects with clinically active treatment-refractory SLE. The study population will include subjects with active LN (as defined by evidence of active inflammation on renal biopsy, referred to as the LN cohort) and subjects with active SLE without LN (ie, non-LN SLE, referred to as the non-LN cohort). It is expected that the safety profile of UB-VV410 will be similar in subjects with active LN and subjects with active non-LN SLE; thus, dose finding (DF) will be conducted in the 2 subpopulation cohorts combined. Dose expansion (DE) may be conducted separately in the LN and non-LN cohorts to characterize the preliminary efficacy of UB-VV410, as well as its safety and PK/PD, in each subpopulation.

The objective of this study is to determine the MTD/MAD and the recommended dose for subsequent studies of UB-VV410 in subjects with active LN and in subjects with active non-LN SLE. The DF portion will evaluate the safety profile of UB-VV410 administered at various DLs. The DE portion will further optimize the dose and define the safety profile and preliminary efficacy of UB VV410. The study will use the Bayesian optimal interval (BOIN) design to allocate subjects to various DLs to minimize exposure to subtherapeutic DLs while maintaining appropriate safety parameters. DF will be initiated with UB-VV410 administered IV and starting at DL1.

During DF, additional subjects may be backfilled at DLs found to be safe per the BOIN design and with promising activity. After DF of UB-VV410 has been completed, DE with up to 14 subjects per DL within each subpopulation cohort (eg, LN and non-LN cohorts) may be implemented at DLs less than or equal to the MTD/MAD and demonstrating efficacy to further characterize the toxicity, tolerability, PK/PD, and preliminary efficacy of UB-VV410 at the selected DLs. The DE portion will further characterize product safety and preliminary efficacy in order to optimize benefit/risk. The number of DLs for DE will be determined based on the safety, activity and PK/PD data observed from DF.

In addition, some subjects may receive retreatment with UB-VV410 if there are preliminary findings suggesting incomplete improvement and acceptable safety.

Conditions

Systemic Lupus Erythematosus; Lupus Nephritis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

treatment group

Interventions: UB-VV410. Subjects will be consented and screened. Once subject eligibility is confirmed, the Investigator will be notified which dose the subject is assigned to receive. Eligible subjects will receive UB-VV410 at the assigned DL on Study Day 1 (Day 1). Dose-limiting toxicities (DLTs) will be assessed for 28 days after UB-VV410 treatment. Safety will be assessed throughout the study. SLE/LN disease activity will be evaluated at approximately 1, 2, 3, 6, 9, 12, 18, and 24 months following UB VV410 administration.

Group Type: EXPERIMENTAL

UB-VV410

Intervention Type: DRUG

Treatment with single dose of UB-VV410, intravenous injection at Day 1. Note: Subjects may receive retreatment with UB-VV410 if there are preliminary findings suggesting incomplete improvement and acceptable safety.

Interventions

UB-VV410

Treatment with single dose of UB-VV410, intravenous injection at Day 1. Note: Subjects may receive retreatment with UB-VV410 if there are preliminary findings suggesting incomplete improvement and acceptable safety.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 at time of consent.

2. Provide voluntary written informed consent.

3. Documented medical records indicated SLE diagnosis or diagnosis of SLE according to the 2019 EULAR/ACR classification criteria for SLE for at least 6 months.

4. Current or history of elevated anti-dsDNA and/or elevated anti-Smith antibody.

5. Alanine aminotransferase (ALT) ≤ 2.5 × ULN, aspartate aminotransferase (AST) ≤ 2.5 × ULN, AND total bilirubin < 1.5 × ULN (or AST, ALT, and alkaline phosphatase < 5 × ULN, and total bilirubin ≤ 3 × ULN for subjects with Gilbert's syndrome

6. No ongoing coagulopathies requiring periodic replacement of clotting factors (eg, fresh frozen plasma, cryoprecipitate). Note: Subjects on a stable anticoagulant regimen > 6 months with activated partial thromboplastin time (APTT) ≤ 2.5 × ULN and international normalized ratio (INR) > 2 and < 3 are allowed on study.

7. No serious concomitant diseases or active/uncontrolled infections.

8. For LN-specific subjects: Active, biopsy-proven, proliferative LN with the classification of Class III or Class IV according to the 2018 revised ISN/RPS criteria. Note: Overlapping Class V is allowed.

9. For Non-LN SLE-specific subjects: SLEDAI-2K score of ≥ 8 (including at least 4 points from non-laboratory assessments; ) and at least 2 BILAG B organ system scores, and/or at least 1 BILAG A organ system score, including, but not limited to, cardiac (peri- or myocarditis), respiratory (pleuritis or lung involvement), vascular, hematological and musculoskeletal.

Exclusion Criteria

1. Women who are pregnant or breastfeeding.

2. BILAG A for neuropsychiatric SLE.

3. Any acute, severe lupus-related flare that needs immediate treatment, such as acute pericarditis, catastrophic antiphospholipid syndrome, or acute CNS lupus (eg, psychosis, seizure).

4. Diagnosis of drug-induced SLE rather than idiopathic SLE.

5. Receiving hemodialysis or peritoneal dialysis.

6. History of previous bone marrow transplantation, gene therapy, adoptive cell transfer, or any kind of CAR T-cell therapy.

7. History of or active human immunodeficiency virus (HIV) infection.

8. Active hepatitis B (HepB) or hepatitis C (HepC). Note: Subjects with negative HepB virus DNA or a negative HepC virus RNA assay for viral load quantifications are permitted. Additionally, subjects who are positive for HepB surface antigen and/or anti-HepB core antibody with a negative HepB virus DNA are eligible.

9. Allergies to supportive medications required for CAR T-cell toxicity management (eg, tocilizumab).

10. Ongoing CNS diseases (eg, seizure disorder, tremor, history of cerebral vascular accident [CVA]/recurrent transient ischemic attack [TIA], cerebritis, substantial psychiatric disorder) that would preclude evaluation of immune effector cell-associated neurotoxicity syndrome (ICANS).

11. Serious and/or uncontrolled medical condition that, in the Investigator's judgment, would cause an unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol.

12. Major surgery within 12 weeks prior to administration of UB-VV410 or plans to undergo major surgery during the trial period and whom the Investigator considers to be at unacceptable risk.

13. Actively receiving treatment in other interventional clinical trials. Note: continued follow-up on previous trials is allowed for survivorship, but no further investigational agents or assessments will be allowed.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: collaborator

Nanjing IASO Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Huijuan Mao, Doctor

Role: PRINCIPAL_INVESTIGATOR

Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University

Central Contacts

Yue Wan, Bachelor

Role: CONTACT

yue.wan@iasobio.com

+86-18896500535

Other Identifiers

UB-VV410CI002

Identifier Type: -

Identifier Source: org_study_id