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.
Brief Title
Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
(212) 263-0372
Central Contact Email
Mala.Masson@nyulangone.org
Completion Date
Completion Date Type
Estimated
Conditions
Systemic Lupus Erythematosus
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)
* 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)
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
Hydroxychloroquine
systemic lupus erythematosus
elderly lupus disease
lupus
sle
plaquenil
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
60 Years
NCT Id
NCT05799378
Org Class
Other
Org Full Name
NYU Langone Health
Org Study Id
23-00071
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
Number of participants who experience moderate or severe flares as defined by the rSFI.
Outcome Measure
Number of Participants who Develop Moderate or Severe Flare based on the Revised SELENA SLEDAI Flare Index (rSFI)
Outcome Time Frame
Up to Month 12
Secondary Outcomes
Outcome Description
Number of participants who experience moderate flares as defined by the rSFI.
Outcome Time Frame
Up to Month 12
Outcome Measure
Number of Participants who Develop Moderate Flare based on rSFI
Outcome Description
The Physician Global Assessment (PGA) of treatment response measures the overall response to treatment as assessed by the physician. The score ranges from +4 to (-4), where 4 = Markedly Improved, 0 = No change, and (-4) = markedly worse.
Outcome Time Frame
Month 12
Outcome Measure
Physician Global Assessment (PGA) Score at Month 12
Outcome Time Frame
Up to Month 12
Outcome Measure
Number of Participants who Begin Prednisone Treatment
Outcome Time Frame
Up to Month 12
Outcome Measure
Number of Participants who Increase Prednisone Use
Outcome Description
Thromboembolic event includes, but is not limited to, venous thrombosis.
Outcome Time Frame
Up to Month 12
Outcome Measure
Number of Participants who Experience Thromboembolic Event
Outcome Time Frame
Up to Month 12
Outcome Measure
Number of Participants who Experience Cardiovascular Event
Outcome Time Frame
Up to Month 12
Outcome Measure
Number of Participants with New-Onset Diabetes
Outcome Time Frame
Up to Month 12
Outcome Measure
Number of Participants with New Retinal Toxicity
Outcome Description
The SF-36 is 36-item self-rated measure of quality of life. A scoring algorithm is used to convert the raw scores into a range from zero (the respondent has the worst possible health) to 100 where the respondent is in the best possible health.
Outcome Time Frame
Baseline, Month 12
Outcome Measure
Change in 36-Item Short Form Survey Instrument (SF-36) Score
Outcome Description
PROMIS-29 consists of 29 questions rated on a scale from 1-5. The raw score is converted to a final T-score metric with a mean T-score of 50 and a standard deviation of 10. The final score ranges from 0 (worst possible outcome) to 100 (best possible outcome). The questionnaire assesses seven domains - depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and ability to participate in social roles and activities.
Outcome Time Frame
Baseline, Month 12
Outcome Measure
Change in 29-Question Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
60