Clinical trial • Phase IV • Musculoskeletal

HYDROXYCHLOROQUINE SULFATE for Rheumatoid arthritis

Phase IV trial of HYDROXYCHLOROQUINE SULFATE for Rheumatoid arthritis.

Overview

Trial Therapeutic Area
Musculoskeletal
Trial Disease
Rheumatoid arthritis
Trial Stage
Phase IV
Drug Modality
Small molecule|Monoclonal antibody|Peptide/protein/enzyme

Key dates

Initial CTIS Submission Date
11-10-2024
First CTIS Authorization Date
12-11-2024

Trial design

Randomised, open-label, comparator arms listed in part i: prednisolone (betamethasone sodium phosphate) - max daily dose 20 mg (route: oral); sulfasalazine - max daily dose 2 g (route: oral); hydroxychloroquine sulfate - max daily dose 5 mg/kg (route: oral); triamcinolone hexacetonide 20 mg/ml suspension for injection (intra-articular) - max daily volume 4 ml. (no specific schedules detailed in part i.)-controlled Phase IV trial in Denmark, Iceland, Sweden and others.

Randomised
Yes
Open Label
Yes
Comparator
Comparator arms listed in Part I: PREDNISOLONE (betamethasone sodium phosphate) - max daily dose 20 mg (route: oral); SULFASALAZINE - max daily dose 2 g (route: oral); HYDROXYCHLOROQUINE SULFATE - max daily dose 5 mg/kg (route: oral); Triamcinolone Hexacetonide 20 mg/ml suspension for injection (intra-articular) - max daily volume 4 ml. (No specific schedules detailed in Part I.)
Target Sample Size
705
Trial Duration For Participant
625

Eligibility

Recruits 705 No vulnerable population selected. Subjects must be ≥18 years and able and willing to provide written informed consent. Subject information and informed consent forms are provided (country-specific ICFs available for participating Member States)..

Pregnancy Exclusion
Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study or within 150 days after the last dose of study medication.
Vulnerable Population
No vulnerable population selected. Subjects must be ≥18 years and able and willing to provide written informed consent. Subject information and informed consent forms are provided (country-specific ICFs available for participating Member States).

Inclusion criteria

  • {"criterion_text":"- Subject is ≥18 years of age.\n- Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol.\n- Subjects must be able and willing to self-administer s.c. injections or have a qualified person available to administer s.c. injections.\n- Subject has a diagnosis of RA as defined by the newly established ACR/EULAR criteria, 2010.\n- <24 months from arthritis symptom debut (symptom duration will be registered).\n- Subject must have DAS28 (CRP) > 3.2.\n- ≥ 2 swollen joints AND ≥ 2 tender joints (based on 66/68 joint count)\n- Subject must fulfill one of the following three criteria: RF positive OR ACPA positive OR CRP ≥10 mg/L.\n- Female subject is either not of childbearing potential (postmenopausal, surgically sterile etc.), or is of childbearing potential and practicing one of the following methods of birth control throughout the study and for 150 days after study completion: •\tIntrauterine device (IUD) •\tContraceptives (oral, parenteral, patch) for three months prior to study drug administration) •\tA vasectomized partner\n- Female subjects of childbearing potential must have a negative pregnancy test at the Screening visit.\n- Subject is judged to be in good general health as determined by the principal investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray (CXR), and 12-lead electrocardiogram (ECG) performed at Screening."}

Exclusion criteria

  • {"criterion_text":"- Subject has been previously treated with disease modifying antirheumatic drugs (DMARDs) for rheumatic diseases\n- Subject has a poorly controlled medical condition, such as uncontrolled diabetes, unstable heart disease, congestive heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the investigator, would put the subject at risk by participation in the study.\n- Subject has a history of clinically significant hematologic (e.g., severe anemia, leukopenia, thrombocytopenia), renal or liver disease (e.g., fibrosis, cirrhosis, hepatitis).\n- Subject has history of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease and/or diagnosis of central demyelinating disease.\n- Subject has history of cancer or lymphoproliferative disease. Allowable exceptions: a.\tSuccessfully treated cutaneous squamous cell or basal cell carcinoma b.\tLocalized carcinoma in situ of the cervix c.\tCuratively treated malignancy (treatment terminated) > 5 years prior to screening\n- Subject has a history of listeriosis, histoplasmosis, untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous (iv) anti-infectives within 30 days or oral anti-infectives within 14 days prior to the BL visit.\n- Subjects will be evaluated for latent TB infection with a PPD or QuantiFERON test and X-ray. Subjects with evidence for latent TB will not be enrolled but first assessed according to local guidelines.\n- Subject is known to have immune deficiency, history of Human Immunodeficiency Virus (HIV) or is otherwise severely immunocompromised.\n- Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study or within 150 days after the last dose of study medication.\n- Men who are planning to father a child during the time they are included in the study.\n- Subject has a history of clinically significant drug or alcohol usage in the last year.\n- Current active inflammatory joint disease other than RA.\n- Subject has a chronic widespread pain syndrome.\n- Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study\n- Subject is unwilling to comply with the study protocol.\n- Screening clinical laboratory analyses show any of the following abnormal laboratory results: a. Aspartate transaminase (AST) or alanine transaminase (ALT) > 1.75 times upper limit of normal (ULN). b. Positive serum human chorionic gonadotropin (hCG). c. Positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C serology indicative of current infection. d. Creatinine levels > 2x the ULN. If creatinine 1-2 times ULN, check GFR. e. Hemoglobin < 90 g/L. f.\tAbsolute neutrophil count (ANC) < 1.5 x 10^3/uL. g.\tSerum total bilirubin ≥ 1.5 mg/dL (≥26 micromol/L).\n- Subject has had a dose of prednisone (or equivalent) >7.5 mg/day or has had a dose change within the preceding 4 weeks.\n- Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 4 weeks. Inhaled corticosteroids for stable medical conditions are allowed.\n- Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study).\n- Subject has chronic arthritis diagnosed before age 17 years.\n- Subject has a history of an allergic reaction or significant sensitivity to constituents of study drugs.\n- Subject has been treated with any investigational drug within one month prior to screening visit.\n- Active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization within 4 weeks of screening."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Treatment Part 1: The primary efficacy outcome is the proportion of patients in remission at week 24 from baseline according to CDAI.\n- Treatment Part 1: The primary radiographic outcome is the progression of total Sharp van der Heijde score after 48 weeks from baseline.\n- Treatment Part 2: The primary efficacy outcome is the proportion of patients in remission according to CDAI, at the time point 24 weeks after the dose was first reduced.","definition_or_measurement_approach":"Proportion of patients in remission at week 24 according to CDAI; radiographic progression measured by total Sharp van der Heijde score after 48 weeks; proportion in remission 24 weeks after dose reduction according to CDAI."}

Recruitment

Planned Sample Size
705
Recruitment Window Months
216
Consent Approach
Written informed consent required from each subject (subjects must be able and willing to provide written informed consent). Participants are adults (≥18 years). Subject information and informed consent form documents are provided and country-specific ICFs are available for participating Member States (documents present for Denmark, Iceland, Sweden, Norway).

Geography

Total Number Of Sites
25
Total Number Of Participants
705

Denmark

Earliest CTIS Part Ii Submission Date
25-10-2024
Latest Decision Or Authorization Date
12-11-2024
Processing Time Days
18
Number Of Sites
7
Number Of Participants
182

Sites

Site Name
Regionshospitalet Silkeborg
Department Name
Diagnostic center
Contact Person Name
Tue Wenzel Kragstrup
Contact Person Email
tuekra@rm.dk
Site Name
Aalborg Universitetshospital
Department Name
Reumatologisk Afdeling
Contact Person Name
Line Uhrenholt
Contact Person Email
l.uhrenholt@rn.dk
Site Name
Odense University Hospital
Department Name
Reumatologisk Afdeling C
Contact Person Name
Torkell Ellingsen
Contact Person Email
torkell.ellingsen@rsyd.dk
Site Name
Odense University Hospital
Department Name
Medicinsk afdeling
Contact Person Name
Søren Andreas Just
Contact Person Email
Soeren.Andreas.Just@rsyd.dk
Site Name
Dansk Gigthospital
Department Name
Reumatologisk Afdeling
Contact Person Name
Kim Hørslev-Petersen
Site Name
Rigshospitalet Glostrup
Department Name
Afdeling for Rygkirurgi, Led- og Bindevævssygdomme, COPECARE
Contact Person Name
Merete Hetland
Contact Person Email
merete.hetland.01@regionh.dk
Site Name
Aarhus University Hospital
Department Name
Led- og Bindevævssygdomme
Contact Person Name
Trine Laurberg
Contact Person Email
trinlaur@rm.dk

Iceland

Earliest CTIS Part Ii Submission Date
25-10-2024
Latest Decision Or Authorization Date
30-12-2024
Processing Time Days
66
Number Of Sites
1
Number Of Participants
16

Sites

Site Name
Landspitali
Department Name
Centre for Rheumatology Research
Contact Person Name
Bjorn Gudbjornsson
Contact Person Email
bjorngu@landspitali.is

Sweden

Earliest CTIS Part Ii Submission Date
25-10-2024
Latest Decision Or Authorization Date
12-11-2024
Processing Time Days
18
Number Of Sites
12
Number Of Participants
393

Sites

Site Name
Karolinska University Hospital
Department Name
Department of Gastroenterology, Dermatology and Rheumatology
Contact Person Name
Jon Lampa
Contact Person Email
jon.lampa@regionstockholm.se
Site Name
Universitetssjukhuset Örebro
Department Name
Reumatologmottagningen Universitetssjukhuset Örebro
Contact Person Name
Annika Söderbergh
Site Name
Karolinska University Hospital
Department Name
Department of Gastroenterology, Dermatology and Rheumatology
Contact Person Name
Jon Lampa
Contact Person Email
jon.lampa@regionstockholm.se
Site Name
Skånes Universitetssjukhus, Malmö
Department Name
Reumatologimottagning Malmö
Contact Person Name
Meliha Kapetanovic
Contact Person Email
meliha.c_kapetanovic@skane.se
Site Name
Akademiska sjukhuset
Department Name
Reumatologimottagningen
Contact Person Name
Karin Hjorton
Contact Person Email
karin.hjorton@akademiska.se
Site Name
Skånes Universitetssjukhus, Lund
Department Name
Reumatologimottagning Lund
Contact Person Name
Meliha Kapetanovic
Contact Person Email
meliha.c_kapetanovic@skane.se
Site Name
Reumatologen Sahlgrenska Universitetssjukhuset/Mölndal
Department Name
Reumatologen Sahlgrenska Universitetssjukhuset/Mölndal
Contact Person Name
Anna Rudin
Contact Person Email
anna.rudin@vgregion.se
Site Name
Universitetssjukhuset i Linköping
Department Name
Reumatologiska kliniken
Contact Person Name
Alf Kastbom
Contact Person Email
alf.kastbom@liu.se
Site Name
Falu lasarett
Department Name
Reumatologimottagning Falun
Contact Person Name
Tomas Husmark
Contact Person Email
tomas.husmark@ltdalarna.se
Site Name
Centrum för reumatologi
Department Name
Centrum för reumatologi
Contact Person Name
Per Larsson
Site Name
Västmanlands sjukhus Västerås
Department Name
Reumatologmottagningen
Contact Person Name
Milad Rizk
Site Name
Sahlgrenska Universitetssjukhuset
Department Name
Reumatologen Sahlgrenska Universitetssjukhuset/Sahlgrenska
Contact Person Name
Anna Rudin
Contact Person Email
anna.rudin@vgregion.se

Norway

Earliest CTIS Part Ii Submission Date
25-10-2024
Latest Decision Or Authorization Date
14-11-2024
Processing Time Days
20
Number Of Sites
5
Number Of Participants
114

Sites

Site Name
Helse Moere Og Romsdal HF
Department Name
Department of Rheumatology
Contact Person Name
Maud-Kristine Aga Ljoså
Contact Person Email
postmottak@helse-mr.no
Site Name
St. Olavs Hospital HF
Department Name
Department of Rheumatology
Contact Person Name
David John Stevens
Contact Person Email
David.John.Stevens@stolav.no
Site Name
Universitetssykehuset Nord-Norge HF
Department Name
Nevro-, Hud og Revmatologisk avdeling
Contact Person Name
Gunnstein Bakland
Contact Person Email
gunnstein.bakland@unn.no
Site Name
Diakonhjemmet Sykehus AS
Department Name
Department of Rheumatology
Contact Person Name
Marte Schrumpf Heiberg
Contact Person Email
Marte.Schrumpf@diakonsyk.no
Site Name
Helse Bergen HF
Department Name
Department of Rheumatology
Contact Person Name
Eli Brodin
Contact Person Email
eli.brodin@helse-bergen.no

Sponsor

Primary sponsor

Full Name
Karolinska Institutet
Organisation Type
Educational Institution
Country Of Registered Address
Sweden

Investigational products

Investigational Product Name
HYDROXYCHLOROQUINE
Active Substance
HYDROXYCHLOROQUINE SULFATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
-
Maximum Dose
5 mg/kg milligram(s)/kilogram
Investigational Product Name
ABATACEPT
Active Substance
ABATACEPT
Modality
Peptide/protein/enzyme
Routes Of Administration
SUBCUTANEOUS INJECTION
Route
SUBCUTANEOUS INJECTION
Authorisation Status
-
Maximum Dose
17.86 mg milligram(s)
Investigational Product Name
AZATHIOPRINE
Active Substance
AZATHIOPRINE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
-
Maximum Dose
2.5 mg/kg milligram(s)/kilogram
Investigational Product Name
SULFASALAZINE
Active Substance
SULFASALAZINE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
-
Maximum Dose
2 g gram(s)
Investigational Product Name
METHOTREXATE (sodium formulations)
Active Substance
METHOTREXATE SODIUM
Modality
Small molecule
Routes Of Administration
SUBCUTANEOUS INJECTION|ORAL
Route
SUBCUTANEOUS INJECTION|ORAL
Authorisation Status
-
Maximum Dose
3.57 mg milligram(s)
Investigational Product Name
Cimzia 200 mg solution for injection in pre-filled syringe
Active Substance
CERTOLIZUMAB PEGOL
Modality
Monoclonal antibody
Routes Of Administration
SUBCUTANEOUS INJECTION
Route
SUBCUTANEOUS INJECTION
Authorisation Status
EU/1/09/544/002
Maximum Dose
14.29 mg milligram(s)
Investigational Product Name
LEFLUNOMIDE
Active Substance
LEFLUNOMIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
-
Maximum Dose
20 mg milligram(s)
Investigational Product Name
RoActemra 162 mg solution for injection in pre-filled syringe
Active Substance
TOCILIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
SUBCUTANEOUS INJECTION
Route
SUBCUTANEOUS INJECTION
Authorisation Status
EU/1/08/492/007
Maximum Dose
23.14 mg milligram(s)
Investigational Product Name
RoActemra 20 mg/mL concentrate for solution for infusion
Active Substance
TOCILIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
INFUSION
Route
INFUSION
Authorisation Status
EU/1/08/492/006
Maximum Dose
0.29 mg/kg milligram(s)/kilogram
Investigational Product Name
PREDNISOLONE
Active Substance
BETAMETHASONE SODIUM PHOSPHATE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
-
Maximum Dose
20 mg milligram(s)
Investigational Product Name
Triamcinolone Hexacetonide 20 mg/ml suspension for injection
Active Substance
TRIAMCINOLONE HEXACETONIDE
Modality
Small molecule
Routes Of Administration
INTRA-ARTICULAR INJECTION
Route
INTRA-ARTICULAR INJECTION
Authorisation Status
PL17509/0061
Maximum Dose
4 ml millilitre(s)
Combination Treatment
Yes

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