Study of Anti-Malarials in Incomplete Lupus Erythematosus

  • End date
    Jan 9, 2024
  • participants needed
  • sponsor
    Milton S. Hershey Medical Center
Updated on 9 November 2021
antinuclear antibody


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.


Systemic lupus erythematosus (SLE) causes major organ damage and shortens lifespan in relatively young persons. Early diagnosis and treatment are essential to improving outcomes for SLE patients. However, evidenced-based approaches to early treatment interventions and the appropriate target population for these interventions are not available. We propose that individuals who have positivity for antinuclear antibodies (ANAs) and who also exhibit some of the other features that are used to classify SLE, are at high risk of progressing to the full systemic form of this disease. These individuals, who have significant levels of ANA with 1 or 2 additional items from the lupus classification criteria, are considered to have incomplete lupus erythematosus (ILE). We propose to treat ILE patients with hydroxychloroquine (HCQ) in the "Study of Anti-Malarials in Incomplete Lupus Erythematosus" or SMILE trial. The primary objective is to determine whether HCQ treatment can prevent acquisition of additional clinical and immunologic features that define SLE.

The major secondary objectives are to determine whether HCQ treatment: (1) lessens lupus disease activity as measured by standard scoring indices; (2) improves patient reported outcomes (3) prevents accumulation of immunologic abnormalities including autoantibodies and cytokines and (4) has an acceptable toxicity profile. The specific aims of this proposal are:

  1. To carry out a double-blind, placebo-controlled, multicenter, randomized trial of HCQ vs. placebo in patients with ILE. The study tests the hypothesis that early use of HCQ can modify disease features so that accumulation of abnormalities leading to a classification of SLE can be significantly slowed.
  2. To determine effects of HCQ on disease activity and patient-reported outcomes in patients with ILE.
  3. To characterize the immunologic profile of HCQ in ILE-treated patients. Autoantibodies, cytokines and chemokines will be measured on multiplex arrays for developing insights into underlying mechanisms.
  4. To quantitatively assess the incidence of ophthalmologic toxicity in HCQ-treated ILE patients. All enrolled patients will have standardized ophthalmologic examinations before and after study treatment. Recommendations for use and monitoring in this patient population will be developed.

The SMILE trial will determine whether or not HCQ should be given to ILE patients, will provide insights into the appropriate target population, and will propose candidate biomarkers to guide treatment decisions. While not part of the Precision Medicine Initiative, SMILE is consistent with its goals. It will be the first step towards testing the feasibility of disease prevention studies in SLE and will accumulate biological samples in a repository that will be available to the lupus research community for further in-depth mechanistic studies.

Condition Autoimmune Disease, Dermatomyositis (Connective Tissue Disease), Connective Tissue Diseases, Autoimmune disease, Systemic Lupus Erythematosus, CONNECTIVE TISSUE DISEASE, SYSTEMIC LUPUS ERYTHEMATOSUS
Treatment hydroxychloroquine, Placebo oral capsule
Clinical Study IdentifierNCT03030118
SponsorMilton S. Hershey Medical Center
Last Modified on9 November 2021


Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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
Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data
Inability to comply with the study visit schedule and procedures
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note