The MERINO trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Diakonhjemmet Sykehus AS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

9 Feb 2024 → ongoing

Decision date (initial)

2024-02-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-510523-30-00

EudraCT number

2019-004641-33

ClinicalTrials.gov

NCT04579848

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To explore whether methotrexate can reduce finger joint pain in patients with symptomatic erosive inflammatory hand OA.

Secondary objectives 5

1. 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.
2. To analyze whether methotrexate reduces joint inflammation reflected by both imaging and soluble biomarkers, and potential associations between symptom reduction and reduced inflammation.
3. To determine whether methotrexate treatment reduces structural progression.
4. Exploratory: person and disease characteristics as predictors for treatment response and identify sensitive imaging, soluble and genetic biomarkers for monitoring disease activity.
5. To evaluate the cost effectiveness of methotrexate compared to standard care.

Conditions and MedDRA coding

Erosive hand osteoarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. 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.
2. Hand OA 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.

Exclusion criteria 1

1. • 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 27

1. Fulfillment of Outcome Measures in Rheumatology Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria (all visits).
2. Self-reported finger pain previous 48 hours on a VAS (0-100 mm) (all visits).
3. Self-reported thumb pain previous 48 hours on a VAS (0-100 mm) (all visits).
4. Pain most painful finger joint last 48 hours (VAS) (all visits).
5. Finger pain and thumb base pain (yes/no) on hand diagram (M00, M06).
6. Patient-reported disease activity last 48 hours (VAS) (all visits).
7. Australian/Canadian hand index (AUSCAN) (all visits).
8. Quality-adjusted life years (QALYs) based on the health-related utility scores measured by the generic instrument EQ-5D (all visits).
9. Michigan Hand Outcomes Questionnaire (MHOQ) pain and physical function subscales (M00, M06).
10. Duration of morning stiffness in finger joints (M00, M06)
11. Duration of morning stiffness in thumb base joints (M00, M06)
12. Hospital Anxiety and Depression Scales (HADS) (M00, M06).
13. Pain Catastrophizing Scale (PCS) (M00, M06).
14. Pain Sensitivity Questionnaire (PSQ) (M00, M06).
15. Knee injury and Osteoarthritis Outcome Score (KOOS)-12 (M00, M06).
16. Hip disability and Osteoarthritis Outcome Score (HOOS)-12 (M00, M06).
17. Concomitant medication (all visits).
18. Number of tender and swollen joints (0-30) (all visits).
19. Grip strength (in kg; using a hand dynamometer) (M00, M06, M12).
20. 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).
21. Ultrasound (screening, all visits): number of finger joints with synovial thickening and power Doppler signals.
22. 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
23. MRI (M00, M06): structural progression and synovitis on static and dynamic contrast-enhanced MRI sequences.
24. Serum or plasma markers of extracellular matrix turnover, including collagens and aggrecan, and markers of inflammation (M00, M06, M12).
25. Number of adverse events, serious adverse events, and withdrawals because of adverse events (all visits).
26. Change in synovial cellular composition and gene expression with single-cell RNA sequencing analyses; subgroup analyses, n=16 patients (M00, M06).
27. Self-reported knee pain previous 48 hours on a VAS (0-100) (M00, M06).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Diakonhjemmet Sykehus AS

Sponsor organisation

Diakonhjemmet Sykehus AS

Address

Diakonveien 12

City

Oslo

Postcode

0370

Country

Norway

Scientific contact point

Organisation

Diakonhjemmet Sykehus AS

Contact name

Coordinator

Public contact point

Organisation

Diakonhjemmet Sykehus AS

Contact name

Coordinator

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

Documents 8 files

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

Application history

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