E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Norwegian adult males and females with symptomatic erosive inflammatory hand osteoarthritis. |
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E.1.1.1 | Medical condition in easily understood language |
Erosive hand osteoarthritis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016686 |
E.1.2 | Term | Finger osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019115 |
E.1.2 | Term | Hand osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064565 |
E.1.2 | Term | Erosive osteoarthritis |
E.1.2 | System Organ Class | 100000004859 |
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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 |
To explore whether methotrexate can reduce finger joint pain in patients with symptomatic erosive inflammatory hand osteoarthritis. |
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E.2.2 | Secondary objectives of the trial |
• To explore whether methotrexate can improve other patient-reported outcomes (such as physical function, stiffness, health-related quality of life), markers of pain sensitization and grip strength. • To analyze whether methotrexate reduces joint inflammation reflected by both imaging and soluble biomarkers, and potential associations between symptom reduction and reduced inflammation. • To determine whether methotrexate treatment reduces structural progression. • Exploratory: person and disease characteristics as predictors for treatment response and identify sensitive imaging, soluble and genetic biomarkers for monitoring disease activity. • To evaluate the cost effectiveness of methotrexate compared to standard care. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
MERINO knee biopsy sub-study |
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E.3 | Principal inclusion criteria |
• Finger joint pain 40-80 on 0-100 VAS with insufficient pain relief from, inability to tolerate or contra-indications to oral paracetamol and/or NSAIDs, and hand symptoms (pain, aching, or stiffness) on most days the previous 6 weeks before randomization. • Hand osteoarthritis according to the ACR criteria, at least 1 distal (DIP) or proximal interphalangeal (PIP) joint of the 2nd-5th finger with radiographic pre-erosive (J-phase) or erosive disease (E-phase) according to the Verbruggen-Veys anatomical phase system, and at least two DIP/PIP joints with power Doppler signal of at least grade 1 or grey-scale synovitis of at least grade 2 on ultrasound. |
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E.4 | Principal exclusion criteria |
• Contraindications for methotrexate, such as uncontrolled serious comorbidities, active or recurrent infections, malignancy, pregnancy and drug or substance abuse. • Other autoimmune or inflammatory rheumatic disease, or psoriasis. • Oral or intra-muscular steroids in the previous month. • Intra-articular treatments or aspirations of any kind of any joint in the hands 3 months before inclusion. • Analgesics, unless stable dosage for ≥1 month. • Symptomatic slow-acting drugs for OA (SYSADOA), unless stable dose for ≥3 months. • Disease modifying osteoarthritis drugs (DMOADs). The complete list of exclusion criteria is provided in the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference in self-reported finger joint pain previous 48 hours on a visual analogue scale (VAS; 0-100 mm) at 6 months (M06) of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Patient-reported outcome measures: • Fulfillment of Outcome Measures in Rheumatology Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria (all visits). • Self-reported finger pain previous 48 hours on a VAS (0-100 mm) (all visits). • Self-reported thumb pain previous 48 hours on a VAS (0-100 mm) (all visits). • Pain most painful finger joint last 48 hours (VAS) (all visits). • Finger pain and thumb base pain (yes/no) on hand diagram (M00, M06). • Patient-reported disease activity last 48 hours (VAS) (all visits). • Australian/Canadian hand index (AUSCAN) (all visits). • Quality-adjusted life years (QALYs) based on the health-related utility scores measured by the generic instrument EQ-5D (all visits). • Michigan Hand Outcomes Questionnaire (MHOQ) pain and physical function subscales (M00, M06). • Duration of morning stiffness in finger joints (M00, M06) • Duration of morning stiffness in thumb base joints (M00, M06) • Hospital Anxiety and Depression Scales (HADS) (M00, M06). • Pain Catastrophizing Scale (PCS) (M00, M06). • Pain Sensitivity Questionnaire (PSQ) (M00, M06). • Knee injury and Osteoarthritis Outcome Score (KOOS)-12 (M00, M06). • Concomitant medication (all visits). Clinical outcome measures: • Number of tender and swollen joints (0-30) (all visits). • Grip strength (in kg; using a hand dynamometer) (all visits). • Pain sensitization: Pressure Pain Thresholds (PPT) by digital algometer; temporal summation by punctate probes; Conditioned Pain Modulation (CPM) by blood pressure ischemic test (M00, M06).
Imaging: • Ultrasound (screening, all visits): number of finger joints with synovial thickening and power Doppler signals. • Conventional radiographs (screening, M06, M12): change in radiographic severity according to: o Kellgren-Lawrence scale o Verbruggen-Veys anatomical phase scoring system o Osteoarthritis Research Society International (OARSI) atlas for the presence/severity of osteophytes, joint space narrowing and erosions • MRI (M00, M06): structural progression and synovitis on static and dynamic contrast-enhanced MRI sequences.
Soluble serum/plasma biomarkers: • Serum or plasma markers of extracellular matrix turnover, including collagens and aggrecan, and markers of inflammation (M00, M06, M12).
Safety: • Number of adverse events, serious adverse events, and withdrawals because of adverse events (all visits).
Synovial biopsies from knees (knee OA sub-study): • Change in synovial cellular composition and gene expression with single-cell RNA sequencing analyses; subgroup analyses, n=16 patients (M00, M06). • Self-reported knee pain previous 48 hours on a VAS (0-100) (M00, M06).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Month 1 (M01), 3 (M03), 6 (M06), 9 (M09) and 12 (M12). |
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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 | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
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
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The end of the study is defined as the date of the last visit of the last participant in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |