Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease

Systemic Lupus Erythematosus Clinical Trial

— SHIELD  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05799378
• Other study ID #: 23-00071
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 2024
• Est. completion date: December 21, 2028

Study information

• Verified date: February 2024
• Source: NYU Langone Health
• Contact: Mala Masson
• Phone: (212) 263-0372
• Email: Mala.Masson[@]nyulangone.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 330
• Est. completion date: December 21, 2028
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

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

Locations

Country	Name	City	State
United States	Montefiore Medical Center/Albert Einstein College of Medicine	Bronx	New York
United States	Hackensack Meridian Health	Hackensack	New Jersey
United States	Penn State MS Hershey Medical Center	Hershey	Pennsylvania
United States	University of California, Los Angeles	Los Angeles	California
United States	Columbia University Irving Medical Center/New York Presbyterian	New York	New York
United States	Hospital for Special Surgery	New York	New York
United States	NYC Health + Hospitals/Bellevue	New York	New York
United States	NYU Langone Health	New York	New York
United States	VA NY Harbor Healthcare System	New York	New York
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
NYU Langone Health	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

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