Effects of Stopping Hydroxychloroquine in Elderly Lupus Disease

NCT05799378 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 23-00071
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 10

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.

Conditions

Systemic Lupus Erythematosus

Keywords

Hydroxychloroquine; systemic lupus erythematosus; elderly lupus disease; lupus; sle; plaquenil

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Number of Participants who Develop Moderate Flare based on rSFI

  Up to Month 12

• Physician Global Assessment (PGA) Score at Month 12

  Month 12

• 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

Study Arms (2)

Hydroxychloroquine (HCQ)

EXPERIMENTAL

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

HCQ-Matching Placebo

PLACEBO COMPARATOR

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

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine 200mg capsules. Administered orally.

Hydroxychloroquine (HCQ)

Placebo DRUG

Hydroxychloroquine-matching placebo capsule. Administered orally.

HCQ-Matching Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• NYU Langone Health: lead
• National Institutes of Health (NIH): collaborator

Study Sites (10)

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Hackensack Meridian Health

Hackensack, New Jersey, 07601, United States

RECRUITING

VA NY Harbor Healthcare System

New York, New York, 10010, United States

RECRUITING

NYC Health + Hospitals/Bellevue

New York, New York, 10016, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Hospital for Special Surgery

New York, New York, 10021, United States

RECRUITING

Columbia University Irving Medical Center/New York Presbyterian

New York, New York, 10032, United States

RECRUITING

Montefiore Medical Center/Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

RECRUITING

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Penn State MS Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Peter Izmirly

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• Jill Buyon

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mala Masson

CONTACT

(212) 263-0372; Mala.Masson@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2023
• First Posted: April 5, 2023
• Study Start: June 27, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: Investigators whose proposed use of the data has been approved by co-PIs, Dr. Peter M. Izmirly and Dr. Jill P. Buyon, will be granted access to the data to achieve aims outlined in the approved proposal. Requests should be directed to Peter.Izmirly@nyulangone.org and Jill.Buyon@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Locations

US (10)