SHIELD: Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease

Sponsor

NYU Langone Health (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05799378

Collaborator

National Institutes of Health (NIH) (NIH)

330

Enrollment

Locations

Arms

66.7

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus	Drug: Hydroxychloroquine Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

330 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Jun 30, 2027

Anticipated Study Completion Date :

Dec 21, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hydroxychloroquine (HCQ) Patients will receive a 90-day supply of HCQ at their screening visit, at 2 months, 4 months, 6 months, 8 months, and 10 months. All patients will return their current supply along with a completed dosing diary at each visit and receive a new supply in exchange. The HCQ dose administered will match each patient's dosage of HCQ at enrollment.	Drug: Hydroxychloroquine Hydroxychloroquine 200mg capsules. Administered orally.
Placebo Comparator: HCQ-Matching Placebo Patients will receive a 90-day supply of HCQ-matching placebo at their screening visit, at 2 months, 4 months, 6 months, 8 months, and 10 months. All patients will return their current supply along with a completed dosing diary at each visit and receive a new supply in exchange. The HCQ-matching placebo dose administered will match each patient's dosage of HCQ at enrollment.	Drug: Placebo Hydroxychloroquine-matching placebo capsule. Administered orally.

Arm

Intervention/Treatment

Experimental: Hydroxychloroquine (HCQ)

Patients will receive a 90-day supply of HCQ at their screening visit, at 2 months, 4 months, 6 months, 8 months, and 10 months. All patients will return their current supply along with a completed dosing diary at each visit and receive a new supply in exchange. The HCQ dose administered will match each patient's dosage of HCQ at enrollment.

Drug: Hydroxychloroquine

Hydroxychloroquine 200mg capsules. Administered orally.

Placebo Comparator: HCQ-Matching Placebo

Patients will receive a 90-day supply of HCQ-matching placebo at their screening visit, at 2 months, 4 months, 6 months, 8 months, and 10 months. All patients will return their current supply along with a completed dosing diary at each visit and receive a new supply in exchange. The HCQ-matching placebo dose administered will match each patient's dosage of HCQ at enrollment.

Drug: Placebo

Hydroxychloroquine-matching placebo capsule. Administered orally.

Outcome Measures

Primary Outcome Measures

Number of Participants who Develop Moderate or Severe Flare based on the Revised SELENA SLEDAI Flare Index (rSFI) [Up to Month 12]
Number of participants who experience moderate or severe flares as defined by the rSFI.

Secondary Outcome Measures

Number of Participants who Develop Moderate Flare based on rSFI [Up to Month 12]
Number of participants who experience moderate flares as defined by the rSFI.
Physician Global Assessment (PGA) Score at Month 12 [Month 12]
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.
Number of Participants who Begin Prednisone Treatment [Up to Month 12]
Number of Participants who Increase Prednisone Use [Up to Month 12]
Number of Participants who Experience Thromboembolic Event [Up to Month 12]
Thromboembolic event includes, but is not limited to, venous thrombosis.
Number of Participants who Experience Cardiovascular Event [Up to Month 12]
Number of Participants with New-Onset Diabetes [Up to Month 12]
Number of Participants with New Retinal Toxicity [Up to Month 12]
Change in 36-Item Short Form Survey Instrument (SF-36) Score [Baseline, Month 12]
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.
Change in 29-Question Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score [Baseline, Month 12]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90095
2	Hackensack Meridian Health	Hackensack	New Jersey	United States	07601
3	Montefiore Medical Center/Albert Einstein College of Medicine	Bronx	New York	United States	10461
4	VA NY Harbor Healthcare System	New York	New York	United States	10010
5	NYC Health + Hospitals/Bellevue	New York	New York	United States	10016
6	NYU Langone Health	New York	New York	United States	10016
7	Hospital for Special Surgery	New York	New York	United States	10021
8	Columbia University Irving Medical Center/New York Presbyterian	New York	New York	United States	10032
9	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma	United States	73104
10	Penn State MS Hershey Medical Center	Hershey	Pennsylvania	United States	17033