Examining Distinct Immunophenotypes to Validate and Enhance Rational Treatment in Systemic Lupus

NCT05306873 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: DAIT ALE10
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 10

Brief Summary

The primary purpose of this study is to evaluate the potential effectiveness of 24 weeks of MMF within previously discovered immunologically defined subsets of SLE patients. Treatment effects will be evaluated within the individual immunologically-homogenous subsets defined at screening. This study will also explore and compare pre-randomization gene expression patterns among responders and non-responders to MMF and MMF plus voclosporin, use comprehensive immunophenotyping to study the immunologic changes that accompany treatment- induced disease improvement and to better understand immunologic changes associated with the loss of clinical response.

Conditions

Systemic Lupus Erythematosus

Keywords

Systemic Lupus; Mycophenolate Mofetil; Voclosporin

Outcome Measures

Primary Outcomes (1)

• The Percentage of Participants Who Experience a Stage 2 Treatment Failure at or Before the Stage 2 Week 24 Visit.

  Treatment failure is defined as the first occurrence after randomization (Stage 2) of any of the following events: 1. Methylprednisolone acetate injection or treatment with a new or increased lupus medication, except the occasional use of corticosteroids for reasons not associated with Systemic Lupus Erythematosus (SLE) flare 2. British Isles Lupus Assessment Group (BILAG) flare, defined as any item marked new or worse that could support a BILAG A (severe flare) or 2 organs with items marked new or worse that could support a BILAG B (moderate flare), and if the participant's condition is deemed by the investigator to be "moderately worse" or "much worse" compared to the day of randomization, as assessed by the Clinician Global Impression of Change (CGI-C) 3. Premature permanent discontinuation of study-assigned treatment for any reason

  From Baseline to Stage 2 Week 24

Secondary Outcomes (15)

• Clinical Response in Stage 2, Defined by the BILAG-based Combined Lupus Assessment (BICLA) at Stage 2 Week 24.

  Stage 2 Week 24

• The Proportion of Participants Who Experience a Stage 3 Treatment Failure, After Stage 3 Re-randomization at or Before Completing Stage 3 Week 24.

  From re-randomization to Stage 3 Week 24

• Time to Treatment Failure in Stage 3, Defined as the Interval From the Day of Stage 3 Randomization Until the Day of Treatment Failure.

  Start of Stage 3 up to the day of treatment failure

• Clinical Response in Stage 3, Defined by the BILAG-based Combined Lupus Assessment (BICLA) at Stage 3 Week 24.

  Stage 3 Week 24

• The Incidence of Grade 3 or Higher Related Adverse Events (AEs) in Stage 2

  Stage 2 Day 0 up to Stage 2 Week 48

Study Arms (4)

MMF

EXPERIMENTAL

Participants will receive 500 mg mycophenolate mofetil (MMF) bid for 7 days, followed by 500mg and 1,000mg MMF in divided doses for 7 days. They will then continue at a stable dose of 1,000mg MMF bid. Visits to evaluate AEs, vital signs, hematology and chemistry, study medication compliance, medication use, disease status, participant reported outcomes, and to obtain biomarker samples will occur every 4 weeks after randomization

Drug: Mycophenolate Mofetil

Placebo for MMF

PLACEBO COMPARATOR

Participants will receive 500 mg corresponding mycophenolate mofetil (MMF) placebo bid for 7 days, followed by 500mg and 1,000mg corresponding MMF placebo in divided doses for 7 days. They will then continue at a stable dose of 1,000mg corresponding MMF placebo bid. Visits to evaluate AEs, vital signs, hematology and chemistry, study medication compliance, medication use, disease status, participant reported outcomes, and to obtain biomarker samples will occur every 4 weeks after randomization

Drug: Placebo for Mycophenolate Mofetil

MMF+ Placebo for Voclosporin

EXPERIMENTAL

Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus placebo for voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication

Drug: Placebo for Voclosporin; Drug: Mycophenolate Mofetil

MMF+ Voclosporin

EXPERIMENTAL

Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication

Drug: Voclosporin; Drug: Mycophenolate Mofetil

Interventions

Mycophenolate Mofetil DRUG

Stage 2 Dosing: Week 1: Participants will receive 500mg MMF/Placebo twice daily Week 2: Participants will receive 500mg/Placebo in the morning and 1,000mg MMF/Placebo in the evening Weeks 3-48: Participants will receive 1000mg MMF/Placebo twice daily

Also known as: CellCept, MMF

MMF

Placebo for Mycophenolate Mofetil DRUG

Stage 2 Dosing: Week 1: Participants will receive 500mg MMF/Placebo twice daily Week 2: Participants will receive 500mg/Placebo in the morning and 1,000mg MMF/Placebo in the evening Weeks 3-48: Participants will receive 1000mg MMF/Placebo twice daily

Also known as: CellCept, MMF

Placebo for MMF

Voclosporin DRUG

Weeks 1-24: 23.7 mg Voclosporin (3 x 7.9 capsules) twice daily

Also known as: Lupkynis, Lupkynis(TM)

MMF+ Voclosporin

Placebo for Voclosporin DRUG

Weeks 1-24: 23.7 mg Placebo for Voclosporin (3 x 7.9 capsules) twice daily

MMF+ Placebo for Voclosporin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must meet all of the following criteria to be eligible for randomization as study participants.
• Aged ≥ 18 and ≤ 60 years at the time of informed consent.
• Meets EULAR/ACR 2019 criteria for SLE.
• Moderately severe, active, but non-organ threatening disease. Specifically, signs or symptoms meeting criteria for a minimum of:

You may not qualify if:

• BILAG B (moderate) activity scores in any organ systems; or
• BILAG B (moderate) activity score in any organ systems and a SELENA-SLEDAI score of ≥ 6.
• If there is only 1 BILAG B score:
• If a musculoskeletal BILAG B is scored due to moderate arthritis, where some loss off functional range of movements was present on several days over the last 4 weeks, there must also be a minimum of at least 3 joints that are both tender and swollen due to lupus disease activity in wrists, MCPs or PIPs for the participant to qualify.
• If a mucocutaneous BILAG B is scored due to acute or subacute cutaneous skin eruption, the rash must cover at least 4% of the body surface area for the participant to qualify. Any active discoid lesion or other form of chronic cutaneous lupus would be qualifying.
• Approval, by an adjudication committee of a brief entry packet describing the type, severity and duration of symptoms meeting the minimal criteria for entry. The participant will meet this criterion if the committee is confident of all of the following:
• Convincing diagnosis of SLE,
• Active disease, due to SLE, warranting the potential of dual therapy with potent immune modulators,
• No medical or other condition to contraindicate participation in a placebo-controlled, outpatient study of this design.
• Women of childbearing potential must have a negative serum pregnancy test at screening.
• Able or willing to use reliable methods of contraception, as outlined in the Mycophenolate REMS brochure for health care providers, from 4 weeks prior to first randomization to 6 weeks after completion of the study. This criterion applies to females of reproductive potential.
• Participants who meet the following criterion at the Stage 2 Randomization Visit may proceed to randomization in Stage 2:
• After completion of corticosteroid injection(s) and prior to randomization in Stage 2, the participant and his/her physician must agree that disease activity has improved sufficiently from screening such that randomization is acceptable.
• The physician must score the CGI-C as "moderately better" or "much better" prior to randomization.
• The reference value for the CGI-C should be the investigator's determination of the participant's condition at the Screening Visit.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (10)

UCLA Medical Center: Division of Rheumatology

Los Angeles, California, 90095, United States

Location

Yale University School of Medicine: Rheumatology, Allergy & Immunology

New Haven, Connecticut, 06519, United States

Location

Emory University School of Medicine: Division of Rheumatology

Atlanta, Georgia, 30307, United States

Location

Piedmont Healthcare: Rheumatology Atlanta

Atlanta, Georgia, 30318, United States

Location

Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases

Boston, Massachusetts, 02114, United States

Location

Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases

Manhasset, New York, 11030, United States

Location

Columbia University Medical Center: Department of Medicine, Division of Rheumatology

New York, New York, 10032, United States

Location

University of North Carolina at Chapel Hill; Thurston Arthritis Research Center: Division of Rheumatology, Allergy, and Immunology

Chapel Hill, North Carolina, 27599, United States

Location

Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program

Oklahoma City, Oklahoma, 73104, United States

Location

PennState Health Milton S. Hershey Medical Center: Division of Rheumatology

Hershey, Pennsylvania, 17033, United States

Location

Related Links

• Autoimmunity Centers of Excellence
• National Institute of Allergy and Infectious Diseases
• Division of Allergy, Immunology, and Transplantation

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Mycophenolic Acid; voclosporin

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Joan Merrill, M.D.

  Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: April 1, 2022
• Study Start: November 30, 2022
• Primary Completion: June 13, 2024
• Study Completion: July 11, 2024
• Last Updated: September 9, 2025
• Results First Posted: September 9, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

US (10)