HydroxyChloroquine as steroid-sparing Agent in Extra-pulmonary SARcoidosis. A multicenter, prospective, placebo-controlled, randomized trial. CAESAR

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

30 Jul 2024 → ongoing

Decision date (initial)

2023-04-14

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

DGOS

External identifiers

EU CT number

2022-502155-65-00

ClinicalTrials.gov

NCT05841758

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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

Secondary objectives 7

1. To assess and compare the evolution of the organ-specific response(s) (calculation of the extrapulmonary Physician Organ Severity Tool (ePOST, previously validated in sarcoidosis RCT).
2. To assess and compare the evolution of the global response (evaluation of the complete, partial, stable, or relapse (or progression) response).
3. To assess and compare the evolution of the need of local steroid treatments (evaluation of the type, frequency and dosage of local steroid treatments, allowing cumulative doses calculation).
4. To assess the efficacy of HCQ in maintaining the relapse-free survival over a prolonged period (until M24) (evaluation of the complete, partial, stable, or relapse (or progression) response).
5. To assess and compare the eventual reduction of steroid-related toxicity (side effects) (clinical and biological index).
6. To assess HCQ safety and patients’ adherence (evaluation of electroretinogram or autofluorescence or OCT (following American Academy of Ophthalmology recommendations), and monitoring of eventual Aes).
7. To assess and compare the change in quality of life (evaluation of SF36 questionnaire).

Conditions and MedDRA coding

Extra pulmonary sarcoidosis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. at least 18 years of age
2. non severe sarcoidosis-related non-severe ENT involvement requiring systemic treatment
3. • pathologically proven sarcoidosis as defined by the ATS/ERS/WASOG criteria (the non-severe / severe criteria are defined in Appendix 9 of the protocol)
4. patient able to give free, informed and written consent
5. affiliated to National French social security system
6. nons evere ocular sarcoidosis requiring systemic treatment
7. non severe skin sarcoidosis requiring systemic treatment
8. non severe osseous sarcoidosis requiring systemic treatment
9. non severe sarcoidosis with joint involvement requiring systemic treatment
10. non severe sarcoidosis-related hypercalcemia requiring systemic treatment
11. non severe peripheral nervous system sarcoidosis requiring systemic treatment
12. Symptomatic hypercalciuria >200 mg/24h (24 h urine) OR - > 20 mg/mmol creatinine on urine sample - > 180 mg/g creatinine on urine sample

Exclusion criteria 20

1. severe sarcoidosis involvement requiring another immunosuppressant or anti-TNF antibody or methylprednisolone i.v. pulses
2. patient participating in other interventional research
3. persons under court protection
4. previous (<3 months before screening) or concurrent treatment with immunosuppressants
5. previous treatment with antimalarial drugs (HCQ/CQ) (the patient must have been off plaquenil for at least 12 months)
6. treatment with citalopram, escitalopram, hydroxyzin, domperidone and piperaquine
7. known hypersensitivity or intoloerance to HCQ/CQ or 4-aminoquinoline derivatives and prednisone
8. heart rhythm disorders on EKG (QT prolongation) (except atrial fibrillation)
9. severe ophthalmological impairment or ophthalmological impairment that does not allow ophthalmic monitoring; previous history of maculopathy or retinopathy
10. end-stage lung, liver, cardiac, or renal disease
11. sarcoidosis with central nervous system involvement
12. Provision of effective contraception for the duration of the study (Contraception is considered effective when it consists of one of the following: use of a male condom during all sexual activity and/or efficient oral hormonal contraception (better considered combined contraception) and/or an intrauterine device (IUD) and/or hormone-releasing intrauterine system (IUS) and/or history of bilateral tubal ligation and/or history of vasectomy, provided the male partner is the trial participant's only sexual partner and/or sexual abstinence)
13. cardiac sarcoidosis
14. 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
15. chronic viral (HIV or HBV) infection
16. untreated latent/active tuberculosis
17. pregnancy or lactation (βHCG will be test by blood analysis at inclusion)
18. concurrent vaccination with live vaccines during therapy
19. inability to understand information about the protocol and to sign informed consent or not suitable candidate to comply with the requirements of this study
20. Previous treatment with cortocoids (patient must have been weaned for 3 months)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 7

1. Organ-specific response assessed by calculation of the extrapulmonary Physician Organ Severity Tool (ePOST, previously validated in sarcoidosis RCT) at M0, M1, M3, M6, M12, M18, and M24
2. Global clinical response assessed by the physician as complete, partial, stable, or relapse (or progression) at M0, M1, M3, M6, M12, M18, and M24
3. Type, frequency and dosage of local steroid treatments, allowing cumulative doses calculation at M0, M1, M3, M6, M12, M18 and M24
4. Relapse rate until M24. Remission is defined by either complete or partial response. Relapse is defined as the persistence, or recurrence of existing manifestations and/or the occurrence of new sarcoidosis manifestations requiring substantial treatment modification
5. Frequencies of steroid-associated side-effects monitored clinically and biologically (BMI calculation, blood pressure measurement for arterial hypertension, dosages of glycaemia and HbA1c for diabetes mellitus, dosages of lipids, dosages of bone turnover markers for osteoporosis and clinical evaluation for infections) and Glucocorticoid Toxicity Index (GTI) will be calculated at M0, M1, M3, M6, M12, M18, and M24.
6. HCQ safety will be assessed through initial and annual eye evaluation: electroretinogram or autofluorescence or OCT, and monitoring of eventual AEs. EKG will be performed before study initiation and at M1, M3, M6, M12, M18, and M24. An AE will be considered as serious if it leads to HCQ cessation, hospitalization, or death. Patients’ adherence will be controlled by patient notebooks, pharmacy count of unused tablets and serial dosages of blood HCQ levels (M6 and M12
7. Quality of life will be assessed by the SF36 questionnaire (Annex 16.1) HADS and FAS at M0, M1, M3, M6, M12, M18, and M24

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Dr Jamilloux

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Dr Jamilloux

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications