Study of Anti-Malarials in Incomplete Lupus Erythematosus

NCT03030118 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: STUDY00003506U01AR071077
• Study Type: interventional
• Target: 187
• Locations: 1 country
• Sites: 7

Brief Summary

This project is a multicenter, randomized, placebo-controlled, double-blind clinical trial that is designed to test whether treating patients who are at risk for development of lupus with hydroxychloroquine can slow accumulation of disease features. Effects on clinical progression of symptoms, patient-reported outcomes and changes in the immune markers of response will be measured and toxicity of the treatment will be assessed. This trial is a first step in testing a prevention strategy for lupus.

Conditions

Systemic Lupus Erythematosus

Keywords

hydroxychloroquine

Outcome Measures

Primary Outcomes (1)

• SLICC Score

  The 2012 Systemic Lupus International Collaborating Clinics classification criteria score erythematosus Minimum value = 0 Maximum value = 17 A score of 4 or greater satisfies classification for systemic lupus erythematosus.

  Measured every 12 weeks for 96 weeks.

Secondary Outcomes (10)

• Number of Subjects With Disease Progression

  Measured up to 96 weeks.

• Number of Subjects Meeting Disease Activity Scores Defined Below

  Measured every 12 weeks for 96 weeks.

• Count of Participants With Defined Disease Activity

  Measured every 12 weeks for 96 weeks

• Patient Reported Outcome Physical Function

  Measured every 12 weeks for 96 weeks

• Patient Reported Outcomes Fatigue

  Measured every 12 weeks for up to 96 weeks

Study Arms (2)

Hydroxychloroquine

ACTIVE COMPARATOR

Hydroxychloroquine will be administered as a once daily dose of 200 or 400 mg, based on the patient's weight. Treatment will be for 96 weeks.

Drug: Hydroxychloroquine

Placebo oral capsule

PLACEBO COMPARATOR

Placebo will be administered as one or two capsules as a single daily dose, based on the patient's weight. Treatment will be for 96 weeks.

Drug: Placebo Oral Capsule

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine is classified as an anti-malarial and it is has immunomodulatory functions that make it useful for treatment of autoimmune disorders including systemic lupus erythematosus and rheumatoid arthritis.

Also known as: Plaquenil

Hydroxychloroquine

Placebo Oral Capsule DRUG

An oral capsule placebo is made to match the active intervention medication hydroxychloroquine.

Also known as: Placebo

Placebo oral capsule

Eligibility Criteria

• Age: 15 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Between 15 and 49 years of age, inclusive, at Visit 1.
• Anti-nuclear antibody (ANA) titer of 1:80, or greater, as determined by immunofluorescence assay (IFA).
• Participants must have at least one (but not three or more) additional clinical or laboratory criterion from the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria.
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

You may not qualify if:

• The subject meets the 2012 SLICC classification criteria for SLE at Visit 1 (i.e., ANA plus 3 other criteria, or ANA plus biopsy-proven lupus nephritis).
• The subject has been diagnosed with another autoimmune disorder, other than autoimmune thyroid conditions.
• The subject has fibromyalgia, based on clinical history and exam.
• The subject has previously been or is currently being treated with oral antimalarial agents including hydroxychloroquine, chloroquine, or quinacrine.
• The subject is currently or has been treated with immunosuppressive, immune modifying, or cytotoxic medications as listed in Section 7.2.
• Use of any investigational agent within the preceding 12 months.
• History of primary immunodeficiency.
• Active bacterial, viral, fungal, or opportunistic infection.
• Evidence of infection with human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C.
• Concomitant malignancy or history of malignancy with the exception of adequately treated basal or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• The subject has significant findings on ophthalmological examination that, in the opinion of the examining Ophthalmologist, prevent safe use of hydroxychloroquine.
• The subject has other contraindications to treatment with hydroxychloroquine including pre-existing ocular disease, hepatic impairment, psoriasis, porphyria, or allergy to the drug or class.
• Co-morbidities requiring systemic corticosteroid therapy greater than 10 mg of prednisone per day, or equivalent, or a change in corticosteroid dose within the 3 months prior to Visit 1.
• Starting, stopping, or changing the dose of over the counter or prescription non-steroidal anti-inflammatory drugs (NSAIDs) in the three months prior to Visit 1.
• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (7)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Northwell Health

Great Neck, New York, 11021, United States

Location

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

Penn State MS Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (3)

• Karp DR, Chong BF, James JA, Arriens C, Ishimori M, Wallace DJ, Liao D, Olsen NJ. Mock Recruitment for the Study of Antimalarials in an Incomplete Lupus Erythematosus Trial. Arthritis Care Res (Hoboken). 2019 Nov;71(11):1425-1429. doi: 10.1002/acr.23802.

  PMID: 30369087 BACKGROUND

• Olsen NJ, James JA, Arriens C, Ishimori ML, Wallace DJ, Kamen DL, Chong BF, Liao D, Chinchilli VM, Karp DR. Study of Anti-Malarials in Incomplete Lupus Erythematosus (SMILE): study protocol for a randomized controlled trial. Trials. 2018 Dec 20;19(1):694. doi: 10.1186/s13063-018-3076-7.

  PMID: 30572906 BACKGROUND

• Porta SV, Ugarte-Gil MF, Garcia-de la Torre I, Bonfa E, Gomez-Puerta JA, Arnaud L, Cardiel MH, Alarcon GS, Pons-Estel BA, Pons-Estel G. Controversies in Systemic Lupus Erythematosus: Are We Treating Our Patients Adequately? J Clin Rheumatol. 2022 Mar 1;28(2):e651-e658. doi: 10.1097/RHU.0000000000001803.

  PMID: 34897194 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The number of participants was lower than planned in part due to the restrictions that were in place during the COVID-19 pandemic; some sites were closed for a time.

Results Point of Contact

• Title: Nancy J Olsen MD, Professor of Medicine
• Organization: Penn State Hershey College of Medicine

nolsen@pennstatehealth.psu.edu

717-531-4921

Study Officials

• Nancy J Olsen, MD

  Penn State MS Hershey Medical Center

  PRINCIPAL INVESTIGATOR

• David R Karp, MD PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 15, 2017
• First Posted: January 24, 2017
• Study Start: December 28, 2017
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: September 16, 2025
• Results First Posted: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available after publication of the primary paper, anticipated in last quarter 2025.
• Access Criteria: Reasonable request is defined as having a legitimate and specific purpose for use of the data and ability to accept it in a usable format.

Locations

US (7)