E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of this study is to evaluate the efficacy and safety of LEF/HCQ treatment vs placebo/placebo for the treatment of pSS in subjects with moderate to severe active disease.
|
|
E.2.2 | Secondary objectives of the trial |
Other objectives will be to identify predictive clinical or molecular measures for response to therapy and to pinpoint underlying molecular pathways associated with lack of clinical response.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a subject must meet all of the following criteria.
1. Women and men, aged 18-75 years
2. pSS diagnosed according to the ACR-EULAR 2016 Criteria for pSS
3. ESSDAI ≥5
4. Use of a reliable method of contraception
5. Signed written informed consent
|
|
E.4 | Principal exclusion criteria |
1. Since LEF has teratogenic effects patients who are pregnant or who are wishing to conceive (also men with a female partner of childbearing age) during or within two years after the study are excluded. During the screenings visit, pregnancy will be excluded in all female patients of childbearing age.
2. Patients that breastfeed
3. Patients with therapy resistant hypertension are excluded since this might be aggravated by LEF
4. In case of maculopathy or retinitis pigmentosa the patient will be excluded from participation. Examination by an ophtalmologist will take place on indication.
5. Patients with secondary Sjögren’s Syndrome (Sjögren’s syndrome associated with other connective tissue disease)
6. Patients with hepatic or renal impairment
7. Patients with a severe infection (including hepatitis B,C or HIV)
8. Presence of a malignancy other than mucosa-associated lymphoid tissue lymphoma (MALT lymphoma)
9. Significant cytopenia
10. Concomitant heart- and inflammatory bowel disease
11. Patients suffering from sarcoidosis
12. Usage of HCQ or LEF <6 months prior to inclusion
13. Usage of immunosuppressive drugs, with the exception of a stable dose of non- steroidal inflammatory drugs and a stable, low dose (≤7.5 mg) of oral corticosteroids
14. Inadequate mastery of the Dutch language |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The change in disease activity upon treatment with LEF/HCQ as measured by the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in pSS patients from 0-24 weeks, as compared to treatment with placebo |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, 8, 16, 24 weeks |
|
E.5.2 | Secondary end point(s) |
The change in other clinical measures including: oral dryness (as measured by unstimulated and stimulated whole saliva output), ESSPRI, ocular dryness, serological and systemic inflammatory measures (such as serum IgG, C3, C4, SSA, SSB and RF) upon treatment with LEF/HCQ in pSS patients from 0-24 weeks, as compared to treatment with placebo.
The change in ESSDAI upon treatment with LEF/HCQ in pSS patients at all 24 week intervals, as compared to treatment with placebo. (52 treatment periods LEF/HCQ vs 26 placebo periods)
The change in all other clinical parameters at 24 weeks and at all 24 week intervals of LEF/HCQ vs placebo (52 treatment intervals LEF/HCQ vs 26 placebo intervals)
To validate molecular markers to predict clinical response and molecular markers and pathways associated with lack of response
The difference in composition of the gut and skin microbiome and food intake in patients with primary Sjögren’s syndrome vs. healthy controls at baseline. The change in composition of the gut and skin microbiome at all study visits between placebo and verum group |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, 8, 16, 24, 32, 40, 48 weeks |
|
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 | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |