Overview
Sponsor-declared trial summary
Systemic Sclerosis (SSc) is a rare and orphan disease (DPCM 12 gennaio 2017-GU SG n°65-S.O. n°15 - 18/03/2017), characterized by immunological, vascular and fibrotic abnormalities. The estimated incidence is 18 to 20 cases per million population year and a prevalence of 100 to 300 cases per million population. In Europe the prevalence rate is estimated around 200 per million while in the Italian population around 20000 persons suffer from this form of autoimmune disease.
To evaluate the efficacy and safety of hydroxychloroquine compared to placebo, at the oral dose of 6 mg/kg daily (up to 400 mg/day), in the treatment of early systemic sclerosis (SSc) associated to SSc standard therapies (immunosuppressive and/or vasoactive).
Key facts
- Sponsor
- Azienda Ospedaliero-Universitaria Policlinico Umberto I
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 13 Jul 2023 → 8 Jan 2026
- Decision date (initial)
- 2024-08-12
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- AIFA (Indipendent Research Call)
External identifiers
- EU CT number
- 2024-516050-22-00
- EudraCT number
- 2021-000230-33
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
To evaluate the efficacy and safety of hydroxychloroquine compared to placebo, at the
oral dose of 6 mg/kg daily (up to 400 mg/day), in the treatment of early systemic
sclerosis (SSc) associated to SSc standard therapies (immunosuppressive and/or
vasoactive).
Secondary objectives 1
- To evaluate the effectiveness of adding hydroxychloroquine to standard therapy for SSc on ESScGAI, capillaroscopic parameters and CSURI Index, VAS pain, Morning Stiffness (MS), FACIT Fatigue Index and Raynaud Condition Score (RCS); Assess the tolerability and variation of clinical, laboratory and biomarker parameters from baseline.
Conditions and MedDRA coding
Systemic Sclerosis (SSc) is a rare and orphan disease (DPCM 12 gennaio 2017-GU SG n°65-S.O. n°15 - 18/03/2017), characterized by immunological, vascular and fibrotic abnormalities. The estimated incidence is 18 to 20 cases per million population year and a prevalence of 100 to 300 cases per million population. In Europe the prevalence rate is estimated around 200 per million while in the Italian population around 20000 persons suffer from this form of autoimmune disease.
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10042953 | Systemic sclerosis | 10028395 |
| 20.0 | SOC | 10017947 | Gastrointestinal disorders | 14 |
| 20.0 | SOC | 10047065 | Vascular disorders | 12 |
| 20.0 | SOC | 10021428 | Immune system disorders | 4 |
| 20.0 | SOC | 10028395 | Musculoskeletal and connective tissue disorders | 17 |
| 20.0 | SOC | 10040785 | Skin and subcutaneous tissue disorders | 16 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | treatment Screening phase: Screening visit can occur up to 4 weeks before Visit 1
Main treatment phase: 52 weeks of double blind treatment with Plaquenil 6 mg/kg (up to 400 mg/day) per day or placebo divided in 6 visits. Visits will occur at day 1 and week 4, 12, 24, 36 and 52, respectively.
|
Randomised Controlled | Double | [{"id":90865,"code":1,"name":"Subject"},{"id":90867,"code":3,"name":"Monitor"},{"id":90864,"code":2,"name":"Investigator"},{"id":90868,"code":4,"name":"Analyst"},{"id":90866,"code":5,"name":"Carer"}] | plaquenil: HCQ 6 mg/kg (up to 400 mg/day) per day placebo: Placebo BID |
| 2 | follow up Safety follow-up visit: will occur after maximum 4 weeks after termination visit (52 weeks)
|
Randomised Controlled | Double | [{"id":90870,"code":4,"name":"Analyst"},{"id":90874,"code":5,"name":"Carer"},{"id":90873,"code":2,"name":"Investigator"},{"id":90872,"code":1,"name":"Subject"},{"id":90871,"code":3,"name":"Monitor"}] | plaquenil: HCQ 6 mg/kg (up to 400 mg/day) per day placebo: Placebo BID |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Diagnosis of SSc according 2013 ACR/EULAR criteria for classification of SSc (van den Hoogen et al, 2013).
- Written Informed Consent (IC)(patient must be able and agree to sign an IC according ICH-GCP guidelines and local laws)
- Age >= 18 years
- Disease duration <= 5 years from the first non-Raynaud’s symptom
- Stable SSc standard treatment within 4 weeks prior to Screening visit
- Subjects naïve to treatment with hydroxychloroquine or who have undergone a wash-out period of at least 16 weeks (approximately 3 half-lives of the drug)
Exclusion criteria 13
- Known hypersensytivity to the study drug (active substance or excipients) or derivatives 4-aminoquinolines
- Age < 18 years
- Body weight < 45 kg
- History of retynopathy and/or maculopathy
- History of severe miopathy (other than SSc related)
- Anticoagulant and/or antiplatelet therapy
- History of periferic neuropathy
- History of hypoglycemia
- History of bradycardia (HR<50) or ventricular arrhythmias
- Deficiency of glucose-6-phosphate dehydrogenase
- Unstable SSc or SSc with end-stage organ involvement at Screening or Visit 1
- Pregnant or breast feeding women
- Other contraindicated clinical and / or laboratory conditions
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- To evaluate efficacy of HCQ add-on compared to placebo by assessing changes from baseline of American College of Rheumatology Combined Response Index for Systemic Sclerosis (CRISS)(Khanna D 2009) at week 52.
Secondary endpoints 6
- econdary efficacy endpoints: To evaluate efficacy of HCQ add-on by assessing change from baseline of: 1. European Systemic Sclerosis Global Disease Activity Index (ESScGDAI) at week 52
- Secondary efficacy endpoints: To evaluate efficacy of HCQ add-on by assessing change from baseline of: Visual Analogue Scale (VAS) for pain at weeks 26 and 52
- Secondary efficacy endpoints: To evaluate efficacy of HCQ add-on by assessing change from baseline of:Morning stiffness (MS) duration (in minutes) at weeks 26 and 52
- Secondary efficacy endpoints: To evaluate efficacy of HCQ add-on by assessing change from baseline of:The FACIT fatigue Index at week 26 and 52
- Secondary efficacy endpoints: To evaluate efficacy of HCQ add-on by assessing change from baseline of:Raynaud Condition Score (RCS) scale at week 26 and 52
- Secondary efficacy endpoints: To evaluate efficacy of HCQ add-on by assessing change from baseline of:Naifold Capillaroscopy (NC) main parameters and CSURI (Capillaroscopic Skin Ulcer Risk Index) at week 52
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PLAQUENIL 200 mg compresse rivestite
PRD426123 · Product
- Active substance
- Hydroxychloroquine Sulfate
- Pharmaceutical form
- COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 400 mg milligram(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- P01BA02 — HYDROXYCHLOROQUINE
- Marketing authorisation
- 013967056
- MA holder
- SANOFI S.R.L.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Azienda Ospedaliero-Universitaria Policlinico Umberto I
- Sponsor organisation
- Azienda Ospedaliero-Universitaria Policlinico Umberto I
- Address
- Viale Del Policlinico 155
- City
- Rome
- Postcode
- 00161
- Country
- Italy
Scientific contact point
- Organisation
- Azienda Ospedaliero-Universitaria Policlinico Umberto I
- Contact name
- Valeria Riccieri
Public contact point
- Organisation
- Azienda Ospedaliero-Universitaria Policlinico Umberto I
- Contact name
- Valeria Riccieri
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Center For Outcomes Research And Clinical Epidemiology S.r.l. ORG-100049869
|
Pescara, Italy | On site monitoring, Code 12, Data management, E-data capture, Code 8 |
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ended | 151 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2023-07-13 | 2026-01-08 | 2023-07-13 | 2025-02-27 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 15 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-516050-22-00 | 1 |
| Protocol (for publication) | D1_Protocol 2024-516050-22-00_clean | 1 |
| Protocol (for publication) | D1_Protocol 2024-516050-22-00_eng | 1 |
| Protocol (for publication) | D1_Protocol 2024-516050-22-00_track changes | 1 |
| Protocol (for publication) | D2_Protocol modification_nr 1_2024-516050-22-00 | 1 |
| Protocol (for publication) | D2_Protocol modification_nr 2_2024-516050-22-00 | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank | 1 |
| Subject information and informed consent form (for publication) | Informativa e consenso | 2 |
| Subject information and informed consent form (for publication) | L1_SIS_adults | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material_patient card | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Plaquenil | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2024-516050-22-00_clean | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2024-516050-22-00_eng | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2024-516050-22-00_Italian | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2024-516050-22-00_track changes | 1 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-10 | Italy | Acceptable 2024-08-05
|
2024-08-12 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-08-19 | Italy | Acceptable 2024-09-30
|
2024-10-01 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-01-20 | Italy | Acceptable 2024-09-30
|
2025-01-20 |