E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of the study is to determine the safety for a combination therapy with hydroxychloroquine plus low dose GCs compared to that for high dose GCs at 3 and 9 months in patients with pulmonary sarcoidosis. |
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E.2.2 | Secondary objectives of the trial |
The aim of the study is to determine the non-inferiority in the overall success rate for a combination therapy with hydroxychloroquine plus low dose GCs compared to that for high dose GCs at 3 and 9 months in patients with pulmonary sarcoidosis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Sarcoidosis patients, with parenchymal pulmonary involvement at CXR with or without adenopathy, must have at least one of the following lung disease activity signs: physiologic abnormalities on pulmonary function testing and/or respiratory symptoms, and/or exercise-induced abnormalities. Physiologic abnormalities on pulmonary function testing will be defined as a value of less than 80% predicted of the forced vital capacity (FVC), or DLCO-SB, or PaO2 <= 70 mmHg at rest. Respiratory symptoms will be defined as significant cough and/or dyspnoea. Exercise-induced abnormalities: O2 saturation decrease of at least 5% during 6MWT; distance walked <= 20% of predicted at 6MWT. |
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E.4 | Principal exclusion criteria |
Disease-Related Exclusions: Unable to understand protocol and to sign informed consent; Not suitable candidate to comply with the requirements of this study, in the opinion of the investigator; Cardiac and neurological sarcoidosis or any other organ involvement or related condition requiring high dosage GCs treatment; End stage lung disease at HRCT ; Clinical evidence of active infection; Documented exposure to beryllium; Patients with FEV1 changes after salbutamol inhalation >=20% Medical and Laboratory Exclusions: History of advanced liver cirrhosis or abnormal liver function (SGOT and/or SGPT >= 3 x upper limit of normal); History of unstable cardiac disease; Moderate to severe renal insufficiency; Poorly controlled diabetes (defined by HbA1c >=10); Pregnancy or lactation (childbearing age female must be on effective contraceptive treatment an must undergo pregnancy testing before start the treatment); A tuberculin skin test (5 I.U.) more than 5 mm; Psoriasis; Homozygous glucose-6-phosphatase deficiency; Known hypersensitivity to hydroxychloroquine or 4-aminoquinoline derivatives; Visual field changes attributable to 4-aminoquinolines Concomitant Therapy Exclusions: Any cytotoxic/immunosuppressive agent including but not limited to GCs at dosages higher than those per protocol, azathioprine, cyclophosphamide, methotrexate, and cyclosporine; Any cytokine modulators (including but not limited to etanercept, infliximab, pentoxifylline, thalidomide); Cimetidine, Digoxin, Phenothiazines, and Methadone (in the hydroxychloroquine arm) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Bone Mineral Density. Lumbar spine (L1-L4) bone mineral density will be evaluated at the baseline and month 9 by DXA. The same instrument will be used for serial DXA studies. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |