Hydroxychloroquine as a Steroid-sparing Agent in Extrapulmonary Sarcoidosis

NCT05841758 | Recruiting Phase 4 DMC

• 2 other identifiers: 69HCL21_10542022-502155-65-00
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 21

Brief Summary

Sarcoidosis is a systemic granulomatous disease of unknown aetiology, mainly affecting the lungs and lymphatics. It affects people worldwide (incidence, 4.7-64/100000; prevalence, 1-36/100000/year). Although it is most often a benign acute or subacute condition, sarcoidosis may progress to a disabling chronic disease in 25% of the cases, with severe complications in about 5%, such as lung fibrosis, cardiac or neurosarcoidosis, defacing lupus pernio or blindness due to uveitis. When indicated, corticosteroids (CS) are the mainstay of treatment. Due to the kinetics of granuloma resolution, the usual and quite 'dogmatic' duration of treatment is said to be one year, following four classical steps. The long-term use of CS is hindered by cumulative toxicity and efforts have to be made to taper them, as quickly as possible, to the lowest effective dose. A recent report mentioned 39% of the CS-treated patients requiring a steroid-sparing agent. Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-malarial drugs that have been used since the 1960's as steroidsparing agents on the basis of a landmark study by Siltzbach reporting their efficacy in 43 patients with skin and intrathoracic sarcoidosis. Subsequently, two small randomized controlled trials have shown significant and prolonged improvement on pulmonary symptoms. Only small case series/reports have shown CQ/HCQ efficacy on extra-pulmonary sarcoidosis with response rates ranging from 67 to 100%. Nevertheless, CQ/HCQ are daily used for skin, bone, and joint sarcoidosis, as well as hypercalcemia. Nowadays, HCQ is preferred over CQ because of a lower incidence of gastrointestinal and ocular adverse reactions, which can be minimized by close attention to the dosage and regular retinal examination. Its profile of safety is well-known since it has long been employed to treat systemic lupus erythematous or rheumatoid arthritis. Its action is thought to rely on its ability to accumulate in lysosomes of phagocytic cells, to affect antigen presentation and reduce pro-inflammatory cytokines. The investigator hypothesize that HCQ may be an efficacious add-on therapy for extra-pulmonary sarcoidosis leading to a significant steroid-sparing effect.

Conditions

Sarcoidosis, Pulmonary

Keywords

Sarcoidosis; Hydroxychloroquine; steroid-sparing agent; Extra pulmonary sarcoidosis

Outcome Measures

Primary Outcomes (1)

• Evaluate the steroid-sparing effect of hydroxychloroquine as an add-on therapy in patients with non severe extra-pulmonary sarcoidosis requiring a systemic treatment.

  The primary endpoint is the percentage of patients in remission and off prednisone at month 9, without relapse until month 12. The primary endpoint will thus be assessed at M12. Remission is defined by either complete or partial response. Complete response is defined as the absence of clinical or paraclinical sign of disease activity. Partial response is defined as the persistence of clinical or paraclinical sign of disease activity, which do not require substantial treatment modification (high dose CS, immunosuppressant or anti-Tumor Necrosis Factor (TNF) drugs). Relapse is defined as the persistence, or recurrence of existing manifestations and/or the occurrence of new sarcoidosis manifestations requiring substantial treatment modification.

  at Year 1

Secondary Outcomes (14)

• Organ-specific response assessed by the extra-pulmonary Physician Organ Severity Tool (ePOST)

  at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.

• rate of complete, partial, stable or progression of the disease

  at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.

• Assess the total dose of local steroid treatments

  at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.

• Assess the efficacy of HCQ in maintaining the relapse-free survival over a prolonged period

  at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.

• Assess and compare the eventual reduction of steroid-related toxicity (side effects)

  at Month 0, Month 1, Month 3, Month 6, Month 12, Month 18 and Month 24.

Study Arms (2)

Hydroxychloroquine

EXPERIMENTAL

prednisone (scheduled protocol) + hydroxychloroquine (200-400 mg /day during a 12 months double blind placebo-controlled period, then according to the treating the physician for an additional open period of 12 months)

Drug: Hydroxychloroquine

Placebo arm

PLACEBO COMPARATOR

prednisone (scheduled protocol) + placebo (1-2 tablets/day during a 12 months double blind placebocontrolled period, then the treatment is left to the physician's discretion until M24)

Drug: Placebo

Interventions

Hydroxychloroquine DRUG

Hydroxychloroquine (200-400 mg /day during a 12 months double blind placebo-controlled period)

Hydroxychloroquine

Placebo DRUG

Placebo during a 12 months double blind placebo-controlled period

Placebo arm

Eligibility Criteria

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

You may qualify if:

• at least 18 years of age
• pathologically proven sarcoidosis as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)/World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) criteria
• non severe ocular sarcoidosis requiring systemic treatment
• non severe skin sarcoidosis requiring systemic treatment
• non severe osseous sarcoidosis requiring systemic treatment
• non severe sarcoidosis with joint involvement requiring systemic treatment
• non severe sarcoidosis-related hypercalcemia requiring systemic treatment
• non severe peripheral nervous system sarcoidosis requiring systemic treatment
• non severe sarcoidosis-related non-severe Ear, Nose and Throat (ENT) involvement requiring systemic treatment
• symptomatic hypercalciuria \>200 mg/24h (24 h urine) OR
• \- \> 20 mg/mmol creatinine on urine sample
• \- \> 180 mg/g creatinine on urine sample
• signed informed consent
• affiliated to National French social security system

You may not qualify if:

• severe sarcoidosis involvement requiring another immunosuppressant or anti-TNF antibody or methylprednisolone i.v. pulses
• previous (\<3 months before screening) or concurrent treatment with immunosuppressants
• previous treatment with antimalarial drugs (HCQ/CQ) (patient must have been off plaquenil for at least 12 months)
• treatment with citalopram, escitalopram, hydroxyzin, domperidone and piperaquine
• known hypersensitivity or intolerance to HCQ/CQ or 4-aminoquinoline derivatives and prednisone
• heart rhythm disorders on EKG (QT prolongation) (except atrial fibrillations)
• severe ophthalmological impairment or ophthalmological impairment that does not allow ophthalmic monitoring; previous history of maculopathy or retinopathy
• end-stage lung, liver, cardiac, or renal disease
• sarcoidosis with central nervous system involvement
• cardiac sarcoidosis
• clinical evidence of active infection (including infection with herpes virus and varicella-zoster virus) or severe/unstabilized comorbidity (e.g. moderate to severe heart failure) or unstabilized psychosis
• chronic viral (HIV or HBV) infection
• untreated latent/active tuberculosis
• concurrent vaccination with live vaccines during therapy
• inability to understand information about the protocol and to sign informed consent or not suitable candidate to comply with the requirements of this study

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (21)

Service de Médecine Interne Infectiologie Aïgue Polyvalente- Hôpital Henri Duffaud

Avignon, 84 000, France

RECRUITING

Service de Pneumologie - Hôpital Avicenne

Bobigny, 93000, France

NOT YET RECRUITING

Service de medecine interne - Hôpital Henri Mondor

Créteil, 94000, France

NOT YET RECRUITING

Service de Médecine Interne et Immunologie Clinique - CHU Dijon Bourgogne

Dijon, 21 079, France

NOT YET RECRUITING

Service de medecine interne - Hôpital Claude Huriez

Lille, 59 000, France

NOT YET RECRUITING

Service de medecine interne - Hôpital Duputryen

Limoges, 87 042, France

NOT YET RECRUITING

Service de médecine interne - Hôpital de la Croix Rousse

Lyon, 69004, France

RECRUITING

Service de médecine interne - Hôpital Edouard Herriot

Lyon, 69004, France

NOT YET RECRUITING

Service de médecine interne - Hôpital Lyon Sud

Lyon, 69004, France

NOT YET RECRUITING

Service de médecine interne - Centre Hospitalier Saint Joseph Saint Luc

Lyon, 69007, France

NOT YET RECRUITING

Service de medecine interne - Hôpital Saint Eloi

Montpellier, 34 295, France

NOT YET RECRUITING

Service de medecine interne - Hôpital Hôtel Dieu

Nantes, 44000, France

NOT YET RECRUITING

Service de médecine interne - Hôpital Lariboisière

Paris, 75010, France

NOT YET RECRUITING

Service de medecine interne 2- Hôpital de la Pitié-Salpétrière

Paris, 75013, France

NOT YET RECRUITING

Hôpital Cochin - Médecine interne

Paris, France

NOT YET RECRUITING

Hôpitaux Saint Joseph et Marie LANNELONGUE

Paris, France

NOT YET RECRUITING

Service de Médecine Interne et maladies infectieuses - Hôpital Haut Lévêque

Pessac, 33 604, France

NOT YET RECRUITING

Service de Médecine Interne et Immunologie Clinique - Hôpital Sud

Rennes, 35 2000, France

RECRUITING

Service de medecine interne - Hôpital Nord

Saint-Etienne, 42 055, France

NOT YET RECRUITING

Service de médecine interne - Clinique Saint exupéry

Toulouse, 31077, France

RECRUITING

CHU Tours - Médecine interne

Tours, France

NOT YET RECRUITING

MeSH Terms

Conditions

Sarcoidosis, Pulmonary; Sarcoidosis

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Thomas El Jammal, Dr

CONTACT

04.26.73.26.29; thomas.el-jammal@chu-lyon.fr

Camille BOUCHENY

CONTACT

04 26 73 27 39; camille.boucheny@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2023
• First Posted: May 3, 2023
• Study Start: July 30, 2024
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (21)