Clinical trial • Phase II • Immunology | Musculoskeletal
Hydroxychloroquine sulfate for Primary Sjögren's syndrome
Phase II trial of Hydroxychloroquine sulfate for Primary Sjögren's syndrome.
Overview
- Trial Therapeutic Area
- Immunology | Musculoskeletal
- Trial Disease
- Primary Sjögren's syndrome
- Trial Stage
- Phase II
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 12-01-2024
- First CTIS Authorization Date
- 20-02-2024
Trial design
Randomised, placebo arms: placebo of hydroxychloroquine; placebo of leflunomide; placebo of mycophenolate mofetil. active investigational products/doses available in protocol: plaquenil 200 mg film-coated tablet (hydroxychloroquine sulfate) — max daily dose 400 mg; arava 20 mg film-coated tablets (leflunomide) — max daily dose 20 mg; mycophenolate mofetil teva 500 mg film-coated tablets — max daily dose 2000 mg.-controlled Phase II trial in Netherlands, Sweden, Italy and others.
- Randomised
- Yes
- Comparator
- Placebo arms: Placebo of hydroxychloroquine; Placebo of leflunomide; Placebo of mycophenolate mofetil. Active investigational products/doses available in protocol: PLAQUENIL 200 mg film-coated tablet (hydroxychloroquine sulfate) — max daily dose 400 mg; Arava 20 mg film-coated tablets (leflunomide) — max daily dose 20 mg; Mycophenolate mofetil Teva 500 mg film-coated tablets — max daily dose 2000 mg.
- Target Sample Size
- 235
- Trial Duration For Participant
- 168
Stratification factors
- Cohort (symptom-based vs systemic activity): ESSPRI ≥5 (high symptoms, low systemic activity) versus ESSDAI ≥5 (moderate/high systemic disease activity)
Eligibility
Recruits 235 No vulnerable population selected. Participants must provide written informed consent prior to any study-related procedures (inclusion criteria). Age < 18 years are excluded. Informed consent documents for adults are available (e.g. L1_SIS and ICF adults - GR)..
- Pregnancy Exclusion
- Pregnant or breastfeeding women or women wanting to conceive either during or within two years after the end of the treatment period
- Vulnerable Population
- No vulnerable population selected. Participants must provide written informed consent prior to any study-related procedures (inclusion criteria). Age < 18 years are excluded. Informed consent documents for adults are available (e.g. L1_SIS and ICF adults - GR).
Inclusion criteria
- {"criterion_text":"- Cohort 1 : Having given written informed consent prior to undertaking any study-related procedures"}
- {"criterion_text":"- Cohort 2 : Use highly reliable contraception during study treatment from the screening and for two years after stopping treatment"}
- {"criterion_text":"- Cohort 1 : Patients with pSS according to ACR/EULAR 2016 criteria or AECG 2002 criteria"}
- {"criterion_text":"- Cohort 1 : With a high level of symptoms (ESSPRI ≥ 5) and low systemic disease activity"}
- {"criterion_text":"- Cohort 1 : Negative pregnancy test (serum at screening)"}
- {"criterion_text":"- Cohort 1 : Use highly reliable contraception during study treatment from the screening and for two years after stopping treatment"}
- {"criterion_text":"- Cohort 2 : Having given written informed consent prior to undertaking any study-related procedures"}
- {"criterion_text":"- Cohort 2 : Patients with pSS according to ACR/EULAR 2016 criteria or AECG 2002 criteria"}
- {"criterion_text":"- Cohort 2 : With moderate/high systemic disease activity, as defined by ESSDAI ≥ 5"}
- {"criterion_text":"- Cohort 2 : Negative pregnancy test (serum at screening)"}
Exclusion criteria
- {"criterion_text":"- Age < 18 years"}
- {"criterion_text":"- Previous treatment with HCQ, LEF, or MMF in the last 3 months"}
- {"criterion_text":"- Previous treatment with rituximab, other B-cell targeted biologic therapy or cyclophosphamide in the last 6 months"}
- {"criterion_text":"- Previous treatment with anti-TNF, abatacept, tocilizumab or belimumab or any other biologic in the setting of a past clinical trial in the last 3 months"}
- {"criterion_text":"- Severe life-threatening systemic involvement requiring cyclophosphamide or high-dose corticosteroids, or any drug considered as an exclusion criteria"}
- {"criterion_text":"- Impairment of other severe immunodeficiency states"}
- {"criterion_text":"- Patients with active malignancy or history of malignancy within the last 5 years except non-melanoma skin cancer"}
- {"criterion_text":"- Patients with active gastrointestinal tract ulceration, hemorrhage and perforation"}
- {"criterion_text":"- Patients with history of cardiomyopathy"}
- {"criterion_text":"- Patients with known hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome"}
- {"criterion_text":"- Serious infection in the past month"}
- {"criterion_text":"- Pregnant or breastfeeding women or women wanting to conceive either during or within two years after the end of the treatment period"}
- {"criterion_text":"- Evidence of active tuberculosis infection"}
- {"criterion_text":"- Active HCV (positive PCR)"}
- {"criterion_text":"- Active HBV infection (positivity for HBS antigen, or positivity for anti-HBC antibody without any HBS antigen)"}
- {"criterion_text":"- HIV infection (positive serology)"}
- {"criterion_text":"- Positive SARS-Cov2 PCR (if vaccinated for COVID-19, no PCR is required; if history of COVID-19 infection, positive serology is sufficient)"}
- {"criterion_text":"- Cytopenia defined as neutrophils < 1.0 G/L, lymphocytes < 0.5 G/L, Hb < 10 g/dl or platelets < 100 G/L"}
- {"criterion_text":"- Moderate to severe renal insufficiency (GFR < 30 ml/min)"}
- {"criterion_text":"- Severe hypogammaglobulinemia defined as gamma globulins or IgG < 5 g/l"}
- {"criterion_text":"- Reduced hepatic function: AST or ALT > 2x ULN"}
- {"criterion_text":"- Prolonged ECG's corrected QT interval (>500 ms)"}
- {"criterion_text":"- Women of childbearing potential not using highly effective methods of contraception"}
- {"criterion_text":"- Known history of maculopathy"}
- {"criterion_text":"- Patients not informed of the risk of alcohol consumption and of the recommendations to avoid alcohol during the entire study"}
- {"criterion_text":"- Not affiliated to a social security regime (specific for France)"}
- {"criterion_text":"- Participation in another interventional trial"}
- {"criterion_text":"- Contra-indication to HCQ: pre-existing retinopathy, hypersensitivity to HCQ or to any of the excipients of the specialty used"}
- {"criterion_text":"- Contra-indication to MMF: hypersensitivity to mycophenolate mofetil, acid mycophenolic, mycophenolate sodium or to any of the excipients of the specialty used"}
- {"criterion_text":"- Contra-indication tor LEF: hypersensitivity to the active substance, the main active metabolite teriflunomide or to any excipients of the specialty used"}
- {"criterion_text":"- Concomitant treatment with corticosteroids more than 10 mg/day of prednisone equivalent at screening or inclusion (randomisation)"}
- {"criterion_text":"- Concomitant treatment with other immunomodulators including methotrexate, azathioprine, cyclophosphamide, cyclosporine and tacrolimus"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Proportion of patients achieving a response according to preliminary STAR at week 24 between each active treatment arm and placebo arm. • Cohort 2: Proportion of patients achieving a response according to preliminary STAR at week 24 between each active treatment arm and placebo arm.","definition_or_measurement_approach":"Response measured as proportion of patients achieving a response according to the preliminary STAR at week 24 (preliminary STAR assessment at Week 24)."}
Recruitment
- Planned Sample Size
- 235
- Recruitment Window Months
- 45
- Consent Approach
- Written informed consent is required from participants prior to undertaking any study-related procedures. Only adults (Age ≥ 18) are eligible (Age < 18 years excluded). An adult informed consent form is available (document: L1_SIS and ICF adults - GR). Study documents (protocol synopses) are provided in multiple languages (translations present: FR, ES, NL, GR, IT, NO, SE).
Geography
- Total Number Of Sites
- 25
- Total Number Of Participants
- 235
Netherlands
- Earliest CTIS Part Ii Submission Date
- 08-02-2024
- Latest Decision Or Authorization Date
- 02-08-2024
- Processing Time Days
- 176
- Number Of Sites
- 2
- Number Of Participants
- 30
Sites
- Site Name
- Universitair Medisch Centrum Groningen
- Department Name
- Rheumatology and Clinical Immunology
- Principal Investigator Name
- Hendrika BOOTSMA
- Principal Investigator Email
- h.bootsma@int.umcg.nl
- Contact Person Name
- Hendrika BOOTSMA
- Contact Person Email
- h.bootsma@int.umcg.nl
- Site Name
- Universitair Medisch Centrum Utrecht
- Department Name
- Division of Internal Medicine and Dermatology, Rheumatology & Clinical Immunology
- Principal Investigator Name
- Helen LEAVIS
- Principal Investigator Email
- H.Leavis@umcutrecht.nl
- Contact Person Name
- Helen LEAVIS
- Contact Person Email
- H.Leavis@umcutrecht.nl
Sweden
- Earliest CTIS Part Ii Submission Date
- 14-02-2024
- Latest Decision Or Authorization Date
- 31-07-2024
- Processing Time Days
- 168
- Number Of Sites
- 3
- Number Of Participants
- 25
Sites
- Site Name
- Lunds Universitet
- Department Name
- Rhumatology
- Principal Investigator Name
- Giovanni CAGNOTTO
- Principal Investigator Email
- giovanni.cagnotto@med.lu.se
- Contact Person Name
- Giovanni CAGNOTTO
- Contact Person Email
- giovanni.cagnotto@med.lu.se
- Site Name
- Karolinska University Hospital
- Department Name
- Rhumatology
- Principal Investigator Name
- Marika KVARNSTROM
- Principal Investigator Email
- marika.kvarnstrom@sll.fr
- Contact Person Name
- Marika KVARNSTROM
- Contact Person Email
- marika.kvarnstrom@sll.fr
- Site Name
- Uppsala University Hospital
- Department Name
- Rhumatology
- Principal Investigator Name
- Gunnel NORDMARK
- Principal Investigator Email
- gunnel.nordmark@medsci.uu.se
- Contact Person Name
- Gunnel NORDMARK
- Contact Person Email
- gunnel.nordmark@medsci.uu.se
Italy
- Earliest CTIS Part Ii Submission Date
- 08-02-2024
- Latest Decision Or Authorization Date
- 19-08-2024
- Processing Time Days
- 193
- Number Of Sites
- 5
- Number Of Participants
- 30
Sites
- Site Name
- Azienda Sanitaria Universitaria Friuli Centrale
- Department Name
- Rheumatology
- Principal Investigator Name
- Luca QUARTUCCIO
- Principal Investigator Email
- luca.quartuccio@asuiud.sanita.fvg.it
- Contact Person Name
- Luca QUARTUCCIO
- Contact Person Email
- luca.quartuccio@asuiud.sanita.fvg.it
- Site Name
- Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
- Department Name
- Rhumatology
- Principal Investigator Name
- Francesco CICCIA
- Principal Investigator Email
- francesco.ciccia@unicampania.it
- Contact Person Name
- Francesco CICCIA
- Contact Person Email
- francesco.ciccia@unicampania.it
- Site Name
- University Hospital Of Perugia
- Department Name
- Rhumatology
- Principal Investigator Name
- Elena BARTOLONI
- Principal Investigator Email
- elena.bartolonibocci@unipg.it
- Contact Person Name
- Elena BARTOLONI
- Contact Person Email
- elena.bartolonibocci@unipg.it
- Site Name
- Fondazione Policlinico Universitario Campus Bio-Medico
- Department Name
- Rhumatology
- Principal Investigator Name
- Roberto GIACOMELLI
- Principal Investigator Email
- r.giacomelli@unicampus.it
- Contact Person Name
- Roberto GIACOMELLI
- Contact Person Email
- r.giacomelli@unicampus.it
- Site Name
- Universita' Di Pisa
- Department Name
- Rhumatology
- Principal Investigator Name
- Chiara BALDINI
- Principal Investigator Email
- chiara.baldini74@gmail.com
- Contact Person Name
- Chiara BALDINI
- Contact Person Email
- chiara.baldini74@gmail.com
France
- Earliest CTIS Part Ii Submission Date
- 08-02-2024
- Latest Decision Or Authorization Date
- 23-07-2024
- Processing Time Days
- 166
- Number Of Sites
- 8
- Number Of Participants
- 70
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Rhumatology
- Principal Investigator Name
- Véronique LE GUERN
- Principal Investigator Email
- veronique.le-guern@aphp.fr
- Contact Person Name
- Véronique LE GUERN
- Contact Person Email
- veronique.le-guern@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Lille
- Department Name
- Internal Medicine
- Principal Investigator Name
- Eric HACHULLA
- Principal Investigator Email
- eric.hachulla@chru-lille.fr
- Contact Person Name
- Eric HACHULLA
- Contact Person Email
- eric.hachulla@chru-lille.fr
- Site Name
- Centre Hospitalier Universitaire De Bordeaux
- Department Name
- Rhumatology
- Principal Investigator Name
- Christophe RICHEZ
- Principal Investigator Email
- christophe.richez@chu-bordeaux.fr
- Contact Person Name
- Christophe RICHEZ
- Contact Person Email
- christophe.richez@chu-bordeaux.fr
- Site Name
- Centre Hospitalier Le Mans
- Department Name
- Rheumatology / Immunology
- Principal Investigator Name
- Paul LEGENDRE
- Principal Investigator Email
- plegendre@ch-lemans.fr
- Contact Person Name
- Paul LEGENDRE
- Contact Person Email
- plegendre@ch-lemans.fr
- Site Name
- Les Hopitaux Universitaires De Strasbourg
- Department Name
- Rhumatology
- Principal Investigator Name
- Jacques-Eric GOTTENBERG
- Principal Investigator Email
- jacques-eric.gottenberg@chru-strasbourg.fr
- Contact Person Name
- Jacques-Eric GOTTENBERG
- Contact Person Email
- jacques-eric.gottenberg@chru-strasbourg.fr
- Site Name
- Assistance Publique Hopitaux De Paris (Le Kremlin-Bicetre)
- Department Name
- Rhumatology
- Principal Investigator Name
- Raphaèle SEROR
- Principal Investigator Email
- raphaele.seror@aphp.fr
- Contact Person Name
- Raphaèle SEROR
- Contact Person Email
- raphaele.seror@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Montpellier
- Department Name
- Rhumatology
- Principal Investigator Name
- Jacques MOREL
- Principal Investigator Email
- j-morel@chu-montpellier.fr
- Contact Person Name
- Jacques MOREL
- Contact Person Email
- j-morel@chu-montpellier.fr
- Site Name
- Centre Hospitalier Regional Et Universitaire De Brest
- Department Name
- Rhumatology
- Principal Investigator Name
- Valérie DEVAUCHELLE-PENSEC
- Principal Investigator Email
- valerie.devauchelle-pensec@chu-brest.fr
- Contact Person Name
- Valérie DEVAUCHELLE-PENSEC
- Contact Person Email
- valerie.devauchelle-pensec@chu-brest.fr
Spain
- Earliest CTIS Part Ii Submission Date
- 08-02-2024
- Latest Decision Or Authorization Date
- 23-07-2024
- Processing Time Days
- 166
- Number Of Sites
- 3
- Number Of Participants
- 30
Sites
- Site Name
- Hospital Clinic De Barcelona
- Department Name
- Rhumatology
- Principal Investigator Name
- Manel RAMOS CASALS
- Principal Investigator Email
- mramos@clinic.cat
- Contact Person Name
- Manel RAMOS CASALS
- Contact Person Email
- mramos@clinic.cat
- Site Name
- Parc Tauli Hospital Universitari
- Department Name
- Rhumatology
- Principal Investigator Name
- Maria Begoña
- Principal Investigator Email
- bmari@tauli.cat
- Contact Person Name
- Maria Begoña
- Contact Person Email
- bmari@tauli.cat
- Site Name
- Vall D'hebron Institut De Recerca
- Department Name
- Rhumatology
- Principal Investigator Name
- Roser SOLANS
- Principal Investigator Email
- rsolanslaq@gmail.com
- Contact Person Name
- Roser SOLANS
- Contact Person Email
- rsolanslaq@gmail.com
Norway
- Earliest CTIS Part Ii Submission Date
- 20-02-2024
- Latest Decision Or Authorization Date
- 25-07-2024
- Processing Time Days
- 156
- Number Of Sites
- 2
- Number Of Participants
- 25
Sites
- Site Name
- Helse Bergen HF
- Department Name
- Rhumatology
- Principal Investigator Name
- Sten DANIEL
- Principal Investigator Email
- sten.daniel.hammenfors@helse-bergen.no
- Contact Person Name
- Sten DANIEL
- Contact Person Email
- sten.daniel.hammenfors@helse-bergen.no
- Site Name
- Helse Stavanger HF
- Department Name
- Medicine
- Principal Investigator Name
- Katrine braekke norheim
- Principal Investigator Email
- katrine.brekke.norheim@sus.no
- Contact Person Name
- Katrine braekke norheim
- Contact Person Email
- katrine.brekke.norheim@sus.no
Greece
- Earliest CTIS Part Ii Submission Date
- 29-03-2024
- Latest Decision Or Authorization Date
- 20-11-2024
- Processing Time Days
- 236
- Number Of Sites
- 2
- Number Of Participants
- 25
Sites
- Site Name
- National And Kapodistrian University Of Athens
- Department Name
- Department of Pathophysiology School of Medicine
- Principal Investigator Name
- Andreas GOULES
- Principal Investigator Email
- agoules@med.uoa.gr
- Contact Person Name
- Andreas GOULES
- Contact Person Email
- agoules@med.uoa.gr
- Site Name
- University General Hospital Of Ioannina
- Department Name
- Department of Internal Medicine
- Principal Investigator Name
- Paraskevi VOULGARI
- Principal Investigator Email
- pvoulgar@uoi.gr
- Contact Person Name
- Paraskevi VOULGARI
- Contact Person Email
- pvoulgar@uoi.gr
Sponsor
Primary sponsor
- Full Name
- Assistance Publique Hopitaux De Paris
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- France
Contract research organisations
- Name
- Pharmacist M. Ltd.
- Responsibilities
- Sponsor/third-party duties (codes: 1,5,7,8,9); contact: i.koukli@pharmassist-cro.com
Third parties
- {"country":"Greece","full_name":"Pharmacist M. Ltd.","duties_or_roles":"sponsorDuties codes: 1,5,7,8,9","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- PLAQUENIL 200 mg, comprimé pelliculé
- Active Substance
- Hydroxychloroquine sulfate
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Authorised (Marketing authorisation number: 34009 364 414 6 0)
- Maximum Dose
- 400 mg per day
- Investigational Product Name
- Arava 20 mg film-coated tablets
- Active Substance
- Leflunomide
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Authorised (Marketing authorisation number: EU/1/99/118/007)
- Maximum Dose
- 20 mg per day
- Investigational Product Name
- Mycophenolate mofetil Teva 500 mg film-coated tablets
- Active Substance
- Mycophenolate mofetil
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- Authorised (Marketing authorisation number: EU/1/07/439/003)
- Maximum Dose
- 2000 mg per day
- Investigational Product Name
- Placebo of hydroxychloroquine
- Modality
- Other
- Investigational Product Name
- Placebo of leflunomide
- Modality
- Other
- Investigational Product Name
- Placebo of mycophenolate mofetil
- Modality
- Other
- Combination Treatment
- Yes
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