Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruitment ended
Participants planned
300
Countries
1
Sites
11
Rheumatoid arthritis according to 2010 criteria
The primary outcomes for the clinical effectiveness consists of 2 parts, namely the difference in (1) proportion of patients using a b- or tsDMARD after 10 months of treatment and (2) disease activity, measured with the disease activity score (DAS) over time. Our tailormade management approach is superior to routine ca…
Key facts
- Sponsor
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 1 Oct 2024 → ongoing
- Decision date (initial)
- 2024-10-01
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Galapagos N.V.
External identifiers
- EU CT number
- 2024-511530-12-01
- EudraCT number
- 2020-002802-21
- ISRCTN
- ISRCTN16170070
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy, Safety
The primary outcomes for the clinical effectiveness consists of 2 parts, namely the difference in (1) proportion of patients using a b- or tsDMARD after 10 months of treatment and (2) disease activity,
measured with the disease activity score (DAS) over time. Our tailormade management approach is superior to routine care if (very) low disease activity is attained faster without the use of more b- or
tsDMARDs (expensive drugs).
The primary outcome for the cost-effectiveness analysis will be the incremental cost-effectiveness ratio (ICER), which is the ratio of the difference in costs to incremental benefits between both management approaches.
Secondary objectives 3
- To investigate if patient reported outcomes, i.e. Self-reported disease activity, functional ability, morning stiffness, general health, pain, fatigue, functional ability, quality of life, worker productivity and social participation, differ between both management approaches
- To evaluate if patient satisfaction, compliance and patient participation is increased with our tailor-made management approach compared to routine care
- To explore whether our tailor-made management approach can be more individualized by adding biomarker(s).
Conditions and MedDRA coding
Rheumatoid arthritis according to 2010 criteria
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 23.1 | LLT | 10062719 | Seronegative rheumatoid arthritis | 10028395 |
| 23.1 | LLT | 10040107 | Seropositive rheumatoid arthritis | 10028395 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | PRIMERA trial Patients will be assessed every 3 months with additional visits at months 1, 2 and 4. At each visit, and two weeks after inclusion, patients will fill out online questionnaires and are seen by the research nurse, who calculates the DAS. Additional blood samples will be taken at baseline (T0) and 1 months (T1) and only at 2 (T2), 3 (T3) and 4 (T4) months if DAS≥2.4 at the previous visit. For the extensive data collection overview we would like to
refer to the full protocol.
|
Randomised Controlled | None | Routine care: Both management approaches use a treat-to-target strategy, aiming for low disease activity (DAS<2.4).18 If DAS≥2.4 treatment is intensified until the aforementioned target is reached. In routine care patients are initially treated with methotrexate (MTX) and GCs once intramuscularly (im). In routine care medication can be intensified every 3 months, reflecting current daily practice. The intensifications steps are in following order: (1) Triple DMARD therapy (TDT), consisting of MTX, sulfasalazine (SASP) and HCQ; (2) MTX + Filgotinib (FIL); (3) MTX + TNF inhibitor (TNFi); and (4) MTX + 2nd TNFi. Tailor-made approach: Both management approaches use a treat-to-target strategy, aiming for low disease activity (DAS<2.4).18 If DAS≥2.4 treatment is intensified until the aforementioned target is reached. The initial therapy of patients randomized to our tailor-made approach depends on the presence of autoantibodies. Patients without autoantibodies will receive hydroxychloroquine (HCQ) + GCs im, while patients with auto-antibodies start with MTX + GCs im. In our tailor-made approach besides the possible 3 monthly treatment intensification, medication alterations can also occur after 1 month and 4 months, depending on the response to respectively GCs im and filgotinib (FIL). A good response to GCs im and FIL after respectively 1 and 4 months is defined as a DAS<2.4 OR ΔDAS>0.6. The intensifications steps in the tailor-made management approach are the same as routine care. |
Regulatory references
- Scientific advice from competent authorities
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Plan to share IPD
- No
- IPD plan description
- Individual participant data are available upon reasonable request.
| EU CT number | Title | Sponsor |
|---|---|---|
| 2020-002802-21 | PeRsonalIzed MEdicine in Rheumatoid Arthritis (PRIMERA trial): a multicenter, single-blinded, randomized controlled trial comparing usual care with a tailor-made approach, Behandeling op maat: Feit of fictie? – Een multicenter, enkelblind gerandomiseerd onderzoek waarin behandeling op maat wordt vergeleken met standaard zorg in nieuw gediagnosticeerde reumatoïde artritis patiënten. | |
| 2024-511530-12-00 | PeRsonalIzed MEdicine in Rheumatoid Arthritis (PRIMERA trial): a multicenter, open-label, randomized controlled trial comparing usual care with a tailor-made approach | Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 2
- Newly diagnosed, DMARD-naive RA patients, according to 2010 criteria
- Age ≥18 years
Exclusion criteria 4
- Current or previous treatment of arthritis with DMARDs
- Glucocorticoids (GCs) in the 3 months prior to randomization
- (Relative) contraindications for study medication: a. Evidence of ongoing infectious or malignant process obtained within 3 months prior to screening and evaluated by a qualified health care professional. b. Pregnant or nursing (lactating) women c. Female participants of child bearing potential and male participants whose partner is of child bearing potential who are not willing to ensure that they or their partner use effective contraception during the trial and for 3 months thereafter as in standard practice. d. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests (LFT) such as aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/ serum glutamic pyruvic transaminase (ALT/SGPT), alkaline phosphatase, or serum bilirubin. The Investigator should be guided by the following criteria: Any single parameter may not exceed 2 x upper limit of normal (ULN). A single parameter elevated up to and including 2 x ULN should be re-checked once more as soon as possible, and in all cases, at least prior to enrollment/randomization, to rule out laboratory error. e. History of renal trauma, glomerulonephritis, or subjects with one kidney only, or a glomerular filtration rate (GFR) < 30 ml/min. f. Other underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions which in the opinion of the Investigator immunocompromises the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy.
- Unable to understand, speak and write in Dutch.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary outcomes for the clinical effectiveness consists of 2 parts, namely the difference in (1) proportion of patients using a b- or tsDMARD after 10 months of treatment and (2) disease activity, measured with the disease activity score (DAS) over time. The primary outcome for the cost-effectiveness analysis will be the incremental cost-effectiveness ratio (ICER), which is the ratio of the difference in costs to incremental benefits between both management approaches.
Secondary endpoints 12
- Disease activity (states) at 10 months, measured with the DAS.
- To investigate whether (changes in) biomarker(s) (levels) can adequately predict treatment response.
- Self-reported disease activity, measured with the Routine Assessment of Patient Index Data 3 (RAPID3).
- Morning stiffness (severity and duration), measured with a 10-point Likert scale.
- General Health, measured with a visual analogue scale (VAS, 0 – 100 mm)
- Fatigue, measured with a visual analogue scale (VAS, 0 – 100 mm)
- Pain, measured with Generalized Pain Questionnaire(GPQ) and PainDetect.
- Functional ability, measured with the health assessment questionnaire (HAQ).
- Quality of life, measured with the Dutch EuroQol questionnaire with 5 dimensions (EQ-5D) with 5 levels.
- Patient satisfaction, compliance and patient participation is respectively measured with the the Treatment Satisfaction Questionnaire for Medication (TSQM) and VAS, the Medication Adherence Report Scale (MARS-5) and the 9-Item Shared Decision Making Questionnaire (SDMQ9).
- The Impact on Participation and Autonomy questionnaire (IPAQ) focuses on autonomy and participation of patients with chronic conditions.
- Worker productivity, measured with the Work Productivity and Activity Impairment (WPAI) questionnaire, which includes presentism and absenteeism.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 12
Humira 40 mg solution for injection in pre-filled syringe
PRD5952357 · Product
- Active substance
- Adalimumab
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 3 mg milligram(s)
- Max total dose
- 480 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AB04 — -
- Marketing authorisation
- EU/1/03/256/003
- MA holder
- ABBVIE DEUTSCHLAND GMBH & CO. KG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cimzia 200 mg solution for injection in pre-filled syringe
PRD2148621 · Product
- Active substance
- Certolizumab Pegol
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 14.29 mg milligram(s)
- Max total dose
- 3000 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AB05 — -
- Marketing authorisation
- EU/1/09/544/004
- MA holder
- UCB PHARMA S.A. (ANDERL BE)
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD11411950 · Product
- Active substance
- Sulfasalazine
- Substance synonyms
- SULPHASALAZINE, SALICYLAZOSULFAPYRIDINE, SASP
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 2000 mg milligram(s)
- Max total dose
- 560000 mg milligram(s)
- Max treatment duration
- 40 Week(s)
- Authorisation status
- Authorised
- ATC code
- A07EC01 — SULFASALAZINE
- Marketing authorisation
- PL 00057/1044
- MA holder
- PFIZER LIMITED
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Simponi 50 mg solution for injection in pre-filled syringe.
PRD3349057 · Product
- Active substance
- Golimumab
- Pharmaceutical form
- SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 3.6 mg milligram(s)
- Max total dose
- 600 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AB06 — -
- Marketing authorisation
- EU/1/09/546/004
- MA holder
- JANSSEN BIOLOGICS B.V.
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Enbrel 50 mg solution for injection in pre-filled syringe
PRD6538802 · Product
- Active substance
- Etanercept
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS INJECTION
- Max daily dose
- 7.14 mg milligram(s)
- Max total dose
- 1200 mg milligram(s)
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AB01 — -
- Marketing authorisation
- EU/1/99/126/017
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Depo-Medrol 80 mg/2 ml Injektionssuspension
PRD1990132 · Product
- Active substance
- Methylprednisolone Acetate
- Pharmaceutical form
- SUSPENSION FOR INJECTION
- Route of administration
- INTRAMUSCULAR INJECTION
- Max daily dose
- 120 mg milligram(s)
- Max total dose
- 720 mg milligram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB04 — METHYLPREDNISOLONE
- Marketing authorisation
- BE061835
- MA holder
- PFIZER S.A.
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Jyseleca 200 mg film-coated tablets
PRD11572414 · Product
- Active substance
- Filgotinib
- Substance synonyms
- G-146034
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 200 mg milligram(s)
- Max total dose
- 200 mg milligram(s)
- Max treatment duration
- 28 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA45 — -
- Marketing authorisation
- EU/1/20/1480/003
- MA holder
- ALFASIGMA S.P.A.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Kenacort-A 40, suspensie voor injectie 40 mg/ml
PRD338432 · Product
- Active substance
- Triamcinolone Acetonide
- Substance synonyms
- 9Α-FLUORO-11Β,21-DIHYDROXY-16Α,17Α-ISOPROPYLIDENEDIOXYPREGNA-1,4-DIENE-3,20-DIONE
- Pharmaceutical form
- SUSPENSION FOR INJECTION
- Route of administration
- INTRAMUSCULAR INJECTION
- Max daily dose
- 80 mg milligram(s)
- Max total dose
- 500 mg milligram(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB08 — TRIAMCINOLONE
- Marketing authorisation
- RVG 05341
- MA holder
- BRISTOL-MYERS SQUIBB B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Remicade 100 mg powder for concentrate for solution for infusion.
PRD3349048 · Product
- Active substance
- Infliximab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 5 mg/kg milligram(s)/kilogram
- Max total dose
- 5 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AB02 — -
- Marketing authorisation
- EU/1/99/116/003
- MA holder
- JANSSEN BIOLOGICS B.V.
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Methotrexate 2,5 mg film-coated tablets
PRD10040098 · Product
- Active substance
- Methotrexate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 3.6 mg milligram(s)
- Max total dose
- 1000 mg milligram(s)
- Max treatment duration
- 40 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BA01 — METHOTREXATE
- Marketing authorisation
- AA084/05702
- MA holder
- REMEDICA LTD
- MA country
- Malta
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Leflunomide Aurobindo 20 mg compresse rivestite con film
PRD10023370 · Product
- Active substance
- Leflunomide
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 40 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AA13 — LEFLUNOMIDE
- Marketing authorisation
- 050037011
- MA holder
- AUROBINDO PHARMA (ITALIA) S.R.L.
- MA country
- Italy
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Hydroxychloroquine sulfate 200mg film-coated Tablets
PRD294373 · Product
- Active substance
- Hydroxychloroquine Sulfate
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 400 mg milligram(s)
- Max treatment duration
- 40 Week(s)
- Authorisation status
- Authorised
- ATC code
- P01BA02 — HYDROXYCHLOROQUINE
- Marketing authorisation
- PL 33271/0001
- MA holder
- BLACKROCK PHARMACEUTICALS LIMITED
- MA country
- United Kingdom
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Sponsor organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Address
- Dr. Molewaterplein 40
- City
- Rotterdam
- Postcode
- 3015 GD
- Country
- Netherlands
Scientific contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Dr. Pascal H.P. de Jong
Public contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Dr. Pascal H.P. de Jong
Locations
1 EU/EEA country · 11 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruitment ended | 300 | 11 |
| Rest of world | — | 0 | — |
Investigational sites
Maasstad Ziekenhuis Stichting
Rheumatology, Maasstadweg 21, 3079 DZ, Rotterdam
Haga Hospital
Rheumatology, Els Borst-Eilersplein 275, 2545 AA, 's-Gravenhage
Universitair Medisch Centrum Utrecht
Rheumatology, Heidelberglaan 100, 3584 CX, Utrecht
Admiraal De Ruyter Ziekenhuis B.V.
Rheumatology, 'S-Gravenpolderseweg 114, 4462 RA, Goes
Sint Franciscus Vlietland Groep Stichting
Rheumatology, Kleiweg 500, 3045 PM, Rotterdam
Medisch Spectrum Twente
Rheumatology, Koningsplein 1, 7512 KZ, Enschede
Leids Universitair Medisch Centrum (LUMC)
Rheumatology, Albinusdreef 2, 2333 ZA, Leiden
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Rheumatology, Dr. Molewaterplein 40, 3015 GD, Rotterdam
Amphia Hospital
Rheumatology, Molengracht 21, 4818 CK, Breda
Albert Schweitzer Ziekenhuis
Rheumatology, Albert Schweitzerplaats 25, 3318 AT, Dordrecht
IJsselland Ziekenhuis
Rheumatology, Prins Constantijnweg 2, 2906 ZC, Capelle Aan Den Ijssel
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 |
|---|---|---|---|---|---|
| Netherlands | 2024-10-01 | 2024-10-01 | 2024-10-01 |
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 EU CT number 2024-511530-12_PRIMERA trial | 4 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PRIMERA trial | 4 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Adalimumab | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Certolizumab pegol | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Etanercept | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Filgotinib | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Golimumab | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Hydroxychloroquine | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Infliximab | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Leflunomide | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Methotrexaat | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Sulfasalazine | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Triamcinolone dd 28-05-2018 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis MS EU CT number 2024-511530-12_PRIMERA trial | 7 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-05 | Netherlands | Acceptable with conditions 2024-10-01
|
2024-10-01 |