RepurpSS-II study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Utrecht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

12 Oct 2021 → 3 Jun 2025

Decision date (initial)

2024-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

ZonMW, the Netherlands

External identifiers

EU CT number

2024-510904-36-00

EudraCT number

2020-001933-11

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To assess clinical efficacy and safety of Leflunomide/Hydroxychloroquine in pSS patients in a phase IIb placebo-controlled randomized clinical trial at 24 weeks, followed by a single-arm crossover and an open extension (total duration of 48 weeks) and to evaluate the capacity of molecular fingerprints in prediction of therapy response

Secondary objectives 2

1. Identify predictive clinical or molecular measures for response to therapy
2. Pinpoint underlying molecular pathways associated with lack of clinical response

Conditions and MedDRA coding

primary Sjögren's Syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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

Exclusion criteria 14

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. The use of reliable contraceptives for the duration of the study up to 2 years after the last study visit is mandatory for all patients (with a partner) 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 conventional and biological DMARDs and dose escalation non-steroidal inflammatory 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The change in ESSDAI upon treatment with LEF/HCQ in pSS patients from baseline to 24 weeks, as compared to treatment with placebo-LEF and placebo-HCQ.

Secondary endpoints 4

1. The change upon treatment with LEF/HCQ in pSS patients from baseline upto 24 weeks, as compared to placebo, in the change in dryness as measured by unstimulated whole unstimulated and stimulated saliva output in pSS patients.
2. The change upon treatment with LEF/HCQ in pSS patients from baseline upto 24 weeks, as compared to placebo, in EULAR Sjögren’s Syndrome Patient Reported Index or ESSPRI (disease activity from patient’s perspective)
3. The change upon treatment with LEF/HCQ in pSS patients from baseline upto 24 weeks, as compared to placebo, in Lachrymal flow measured by Shirmer’s test, Ocular Staining Score and Tear breakup time.
4. The change upon treatment with LEF/HCQ in pSS patients from baseline upto 24 weeks, as compared to placebo, in the change in tender joint count and swollen joint count (68/66).

Investigational products

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

Test 6

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Utrecht

Sponsor organisation

Universitair Medisch Centrum Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

dr. H. Leavis

Public contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

dr. H. Leavis

Locations

1 EU/EEA country · 1 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

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

Application history

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