Clinical trial NCT05799378: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Systemic Lupus Erythematosus
Keywords: Hydroxychloroquine
systemic lupus erythematosus
elderly lupus disease
lupus
sle
plaquenil
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2023-04-05
Enrollment: 330
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 2 months for one year to assess disease activity and flares.


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)

Primary outcomes:
measure: Number of Participants who Develop Moderate or Severe Flare based on the Revised SELENA SLEDAI Flare Index (rSFI)
timeFrame: Up to Month 12
Secondary outcomes:
measure: Number of Participants who Develop Moderate Flare based on rSFI
timeFrame: Up to Month 12
measure: Physician Global Assessment (PGA) Score at Month 12
timeFrame: Month 12
measure: Number of Participants who Begin Prednisone Treatment
timeFrame: Up to Month 12
measure: Number of Participants who Increase Prednisone Use
timeFrame: Up to Month 12
measure: Number of Participants who Experience Thromboembolic Event
timeFrame: Up to Month 12
measure: Number of Participants who Experience Cardiovascular Event
timeFrame: Up to Month 12
measure: Number of Participants with New-Onset Diabetes
timeFrame: Up to Month 12
measure: Number of Participants with New Retinal Toxicity
timeFrame: Up to Month 12
measure: Change in 36-Item Short Form Survey Instrument (SF-36) Score
timeFrame: Baseline, Month 12
measure: Change in 29-Question Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score
timeFrame: Baseline, Month 12
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Hackensack
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center/Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: VA NY Harbor Healthcare System
state: New York
city: New York
country: United States
facility: NYC Health + Hospitals/Bellevue
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center/New York Presbyterian
state: New York
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Hershey
country: United States
facility: Penn State MS Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: NYU Langone Health
name: Peter Izmirly
role: PRINCIPAL_INVESTIGATOR
affiliation: NYU Langone Health
name: Jill Buyon
role: PRINCIPAL_INVESTIGATOR
References: