QUIDOSE. Randomized controlled trial testing the efficacy of hydroxychloroquine combined with low dose corticosteroid therapy in pulmonary sarcoidosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

28 Oct 2024 → ongoing

Decision date (initial)

2024-10-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

French Ministry of Health (PHRC-N 2019)

External identifiers

EU CT number

2024-516101-23-00

EudraCT number

2021-001834-20

ClinicalTrials.gov

NCT05247554

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate the non-inferiority of hydroxychloroquine combined with low-dose corticosteroids versus medium-dose corticosteroid therapy in improving respiratory function at 6 months

Secondary objectives 2

1. To demonstrate the superiority of hydroxychloroquine combined with low-dose corticosteroids versus medium-dose corticosteroid therapy at 3, 6 months, and 1 year on: • General quality of life • Respiratory quality of life • Fatigue • Treatment side effects • Treatment adherence
2. To demonstrate the non-inferiority of hydroxychloroquine combined with low-dose corticosteroids versus medium-dose corticosteroid therapy at 3, 6 months, and 1 year on: • Respiratory function using additional tools • Respiratory symptoms • Activity and flares of thoracic and extra-thoracic sarcoidosis

Conditions and MedDRA coding

Sarcoidosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Aged ≥18 and ≤80 years
2. Pulmonary sarcoidosis meeting ATS 2020 AJRCCM diagnostic criteria ( (i) compatible presentation, (ii) non-necrotizing granuloma in one or more tissues, exclusion of alternative granulomatous diseases)
3. Patient presenting : - Lung activity on imaging (e.g., micronodules, nodules, ground glass, consolidations, septal lines) - And FVC ≤ 80% pred and/or ≥10% absolute decline in FVC from the best FVC or FVC ≤ 90% pred with significant physical performance deterioration in the last year - And one or more respiratory symptom(s) among the following: cough, dyspnea, chest pain
4. Effective contraception for women of childbearing potential until 8 months post-treatment
5. Informed and signed consent
6. Social security coverage

Exclusion criteria 19

1. Severe sarcoidosis requiring immediate and urgent results and/or high-dose corticosteroids (severe/active neurological (except facial nerve involvement), cardiac, ophthalmic (except local treatment-responsive form), laryngeal, renal involvement, severe hypercalcemia, severe hepatic)
2. Cardiomyopathy with heart failure
3. Other conditions affecting respiratory function: moderate to very severe COPD, uncontrolled asthma, obesity (BMI >30), fibrotic pulmonary disease, pulmonary neoplasia
4. Hydroxychloroquine contraindications (hypersensitivity, severe retinal or cataract, unilateral blindness, myasthenia gravis, QTc prolongation, concurrent QT-prolonging drugs)
5. Tamoxifen use
6. Renal insufficiency with clearance <60ml/min
7. History of retinopathy or maculopathy
8. Corticosteroid contraindications (hypersensitivity, infections, evolving virosis, glaucoma, uncontrolled psychosis, live vaccines, uncontrolled diabetes, uncontrolled hypertension)
9. Acute porphyria risk
10. Glucose-6-Phosphate Dehydrogenase deficiency (acute hemodialysis risk)
11. HIV positivity, active Hepatitis B or C
12. Systemic corticosteroid or immunosuppressant use for at least 7 days in the previous 3 months inclusion/randomization
13. History of hydroxychloroquine treatment for sarcoidosis
14. Current pregnancy
15. Breastfeeding
16. Inability to respond to questionnaires despite aid
17. Patient under guardianship or curatorship
18. Patient under judicial protection
19. Participation in another interventional therapeutic trial within 6 months before inclusion

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The difference in forced vital capacity (FVC) percentage of predicted value between baseline and 6 months

Secondary endpoints 12

1. General Quality of Life: Short Form 36 item (SF-36) questionnaire
2. Respiratory Quality of Life: St George's Respiratory Questionnaire (SGRQ)
3. Fatigue: Score Fatigue assessment scale (FAS)
4. Hydroxychloroquine Treatment Side Effects: digestive issues (nausea, vomiting), allergic and skin disorders, ocular effects
5. Corticosteroid Treatment Side Effects : weight, blood pressure, Cushingoid facies, infection episodes, sleep disorders (Pittsburgh Sleep Quality Index - PSQI), anxiety disorders (Hospital Anxiety and Depression Scale - HADS), fasting blood glucose, HbA1c, lipid profile (total cholesterol, TG, HDL-C, LDL-C), nutritional assessment when done as part of care
6. Treatment Adherence: GIRERD self-questionnaire
7. Respiratory Function: Measure of FVC, Forced Expiratory Volume in 1 second (FEV1), Carbon Monoxide Diffusing Capacity (DLCO), oxygen saturation, 6-minute walk test (6MWT). The 3-month follow-up will be aimed at assessing the patient's early respiratory progress, as is done in routine practice
8. Respiratory Symptoms: Dyspnea scores and scales: mMRC, Baseline and Transition Dyspnea Index (BDI-TDI), Dyspnea-12; Cough and Sputum Assessment Questionnaire (CASA-Q)
9. Activity and flares of thoracic and extrathoracic sarcoidosis : Organ involvement assessed clinically using the Wasog sarcoidosis organ assessment instrument adapted by Bickett et al. (Score form)
10. Response to treatment : disappearance/appearance/worsening/improvement/stability of organ involvement using the extra-Pulmonary physician Organ Severity Tool (ePOST)(11), Sarcoidosis-Disease Activity Index (S-DAI)(12)
11. Use of immunosuppressants or increased corticosteroid dose during the study
12. Biological activity assessed by serum angiotensin-converting enzyme (ACE) levels, calcium, lymphocyte count in complete blood count

Investigational products

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

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Florence Jeny

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Florence Jeny

Locations

1 EU/EEA country · 39 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 9 files

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

Application history

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