Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease

Official title

A Phase III, Randomized, Double-Blind Placebo-Controlled, Non-Inferiority, Multi-Center Study of the Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease

Overview

Hydroxychloroquine (HCQ) is a systemic lupus erythematosus (SLE) medication that has been very effective in reducing lupus disease activity and keeping patients stable with reduced symptoms. Despite a track record of safety with regard to infection compared to traditional immunosuppressive agents, the risk of HCQ retinal toxicity escalates with continued use. Evaluation using sensitive standard of care approaches suggests nearly a third of patients accrue retinal damage. Data are needed to accurately weigh the balance between accumulating ocular exposure of HCQ versus the risk of disease flare in a population that may have more inactive disease than younger patients. The purpose of this trial is to address the safety of withdrawal of HCQ in SLE patients =60 years old. The central hypothesis is that HCQ can be safely discontinued in stable/quiescent patients assessed by validated disease activity and flare instruments in the context of serologic, cytokine and transcriptomic profiling. Patients will be randomized to either the placebo or active arm and followed every 3 months for one year to assess disease activity and flares.

Interventions

• Drug Hydroxychloroquine
  Hydroxychloroquine 200mg capsules. Administered orally.
• Drug Placebo
  Hydroxychloroquine-matching placebo capsule. Administered orally.

Primary outcome measures

• Number of Participants who Develop Moderate or Severe Flare based on the Revised SELENA SLEDAI Flare Index (rSFI) [Time frame: Up to Month 12]

Secondary outcome measures (10)

• Number of Participants who Develop Moderate Flare based on rSFI [Time frame: Up to Month 12]
• Physician Global Assessment (PGA) Score at Month 12 [Time frame: Month 12]
• Number of Participants who Begin Prednisone Treatment [Time frame: Up to Month 12]
• Number of Participants who Increase Prednisone Use [Time frame: Up to Month 12]
• Number of Participants who Experience Thromboembolic Event [Time frame: Up to Month 12]
• Number of Participants who Experience Cardiovascular Event [Time frame: Up to Month 12]
• Number of Participants with New-Onset Diabetes [Time frame: Up to Month 12]
• Number of Participants with New Retinal Toxicity [Time frame: Up to Month 12]
• Change in 36-Item Short Form Survey Instrument (SF-36) Score [Time frame: Baseline, Month 12]
• Change in 29-Question Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score [Time frame: Baseline, Month 12]

Eligibility criteria

Inclusion criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Age ≥ 60 years at time of enrollment
• Normal OCT and VF assessment within 6 months of screening visit
• Ability to take oral medication
• Have established SLE (≥ 4 ACR criteria or SLICC criteria or ≥ 10 points by EULAR criteria, SLE diagnosed at least seven years ago)
• Stable disease at screening visit by attaining DORIS remission (meeting all criterion listed below) and not on any immunosuppressants.

• Criterion 1: Clinical SLEDAI= 0
• Criterion 2: SELENA-SLEDAI PGA ≤ 0.5 (on a scale from 0-3, where 0 is no disease activity and 3 is maximum disease activity)
• Criterion 3: Current prednisolone (or equivalent corticosteroid) dose ≤ 5 mg daily
• No moderate or severe flares one year prior to screening
• Taking ≥ 200 HCQ daily for ≥ 7 years

Exclusion criteria

• Any patient that does not attain stable disease status by DORIS
• Ophthalmologic evidence of retinopathy (these patients would be advised to discontinue HCQ and therefore unethical to randomize for this study)
• Clinical SLEDAI > 0
• Taking > 5 mg/day prednisone
• Taking any immunosuppressive drugs or biological agents (including: methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, leflunomide, cyclosporine, cyclophosphamide, tacrolimus, rituximab, and belimumab)
• Any reason the treating rheumatologist is concerned about ongoing activity not captured by SLEDAI
• HCQ level < 100 ng/ml as this would support noncompliance and less reliance on HCQ to control activity
• Patient unwilling or unable to comply with study procedures for any reason
• Any indications of potentially diminished capacity, such as a diagnosis of dementia or cognitive impairment (including, but not limited to stroke-related cognitive impairment)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 12 centers

• University of California, Los Angeles — Los Angeles
• University of California: San Diego — San Diego
• Emory University School of Medicine — Atlanta
• Hackensack Meridian Health — Hackensack
• VA NY Harbor Healthcare System — New York
• NYC Health + Hospitals/Bellevue — New York
• NYU Langone Health — New York
• Hospital for Special Surgery — New York
• … and 4 more centers

Identifiers

NCT: NCT05799378 · 23-00071

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗