Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
128
Countries
1
Sites
10
rheumatoid arthritis (RA)
To compare the efficacy of Methotrexate/Metformin vs. Methotrexate alone on the decrease of RA activity in MTX-naive patients, after 6 months of treatment.
Key facts
- Sponsor
- Centre Hospitalier Universitaire De Bordeaux, Centre Hospitalier Universitaire De Bordeaux
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Phenomena and Processes [G] - Immune system processes [G12]
- Trial duration
- 3 Dec 2020 → ongoing
- Decision date (initial)
- 2024-07-09
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Ministry for Health and Solidarity, France · NORDIC PHARMA SAS
External identifiers
- EU CT number
- 2024-511033-35-00
- EudraCT number
- 2018-004287-56
- ClinicalTrials.gov
- NCT04196868
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Therapy
To compare the efficacy of Methotrexate/Metformin vs. Methotrexate alone on the decrease of RA activity in MTX-naive patients, after 6 months of treatment.
Secondary objectives 7
- Describe the proportion of patients achieving remission (DAS28-ESR ≤ 6.6) at 6, 12 and 24 months in both randomization groups.
- Describe the proportion of patients achieving a low level of activity (DAS28-ESR ≤ 3.2) at 6 months in both randomization groups.
- Describe the mean dose of Methotrexate prescribed at 6, 12 and 24 months in both randomization groups.
- Describe the mean dose of Methotrexate prescribed at 6, 12 and 24 months in both randomization groups.
- Describe clinical and laboratory parameters related to metabolism in both randomization groups.
- Describe the frequency of occurrence of serious adverse events in both randomization groups.
- Describe the quality of life of patients in both randomization groups.
Conditions and MedDRA coding
rheumatoid arthritis (RA)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | HLT | 10039075 | Rheumatoid arthritis and associated conditions | 10021428 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Experimental period Association de metformine et de méthotrexate au méthotrexate seul pendant 6 mois
|
Randomised Controlled | Double | [{"id":63795,"code":2,"name":"Investigator"},{"id":63796,"code":5,"name":"Carer"},{"id":63794,"code":1,"name":"Subject"}] | Experimental: Drugs: Metformin treatment 1500 mg once a day, per os + Methotrexate treatment Period: 6 months (Baseline at M6) Placebo Comparator: Drugs: Placebo per os + Methotrexate treatment Period: 6 months (Baseline at M6) |
| 2 | Following patient Drug : Only Methotrexate after association
Period: 18 months (M6 at M24)
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Patients aged over 18 years old.
- Patient affected by RA according to ACR 2010 criteria.
- DAS28-ESR > 3.2
- Methotrexate naïve patients, or without any methotrexate intake for more than six months.
- Men who accept to take active contraception during the study and during six months after the end of the Methotrexate treatment. Partner of patient will be informed of teratogenicity of MTX and will be advised to be on effective contraceptives for all the study duration.
- Women with a negative test of β-HCG who accept to take active contraception during the study and during six months after the end of the Methotrexate treatment.
- Being affiliated to a health insurance system.
- Having signed an informed consent form (later than the day of inclusion and before any examination required by the research).
Exclusion criteria 19
- Patient who present contraindications to treatment with Methotrexate or Metformin.
- Patient with type 1 or type 2 diabetes.
- Patient with daily corticosteroid treatment at a dosage ≥ 15 mg/day within four weeks before the inclusion.
- History of allergy or intolerance to biguanide.
- Presence of anemia (hemoglobin < _80 g/l), neutropenia (neutrophils count < 1500 mm3), lymphopenia (lymphocytes count < 750 mm3), thrombopenia (platelets < 100 000/mm3) or bone marrow hypoplasia.
- Renal insufficiency with clearance < 50 ml/mn.
- Decompensated heart failure.
- Severe respiratory insufficiency.
- Hepatic insufficiency, or bilirubin level upper than 5mg/dl (85,5µmol/l), or ASAT/ALAT more than twice the standard level.
- Acute or chronic infection, such as tuberculosis or HIV.
- Critical ischemia of the lower limbs.
- Recent stroke.
- Patient with pleural effusion, or ascites.
- Patient with stomatitis, mouth ulcers, or active gastrointestinal ulcer.
- Patient with alcohol intoxication.
- B12 Vitamin deficiency.
- Patient performing or planning to perform a long-fasting period.
- Pregnant or breastfeeding women.
- Patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent).
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Level of RA activity according to Disease Activity score on 28 joints (DAS28).
Secondary endpoints 6
- Proportion of patients who reach remission after 6, 12 and 24 months of treatment (DAS < 2,6).
- Proportion of patients with low disease activity after 6 months of treatment (DAS < 3,2).
- Proportion of patients for which a biologic treatment is introduced after 6, 12 and 24 months of treatment.
- Description of some metabolic parameters within the two groups of treatment: weight loss, waist circumference, fasting glycemia and hemoglobin A1c level (HbA1c), cholesterol levels, triglycerids, insulinemia, and bilirubin.
- Proportion of patients who present a serious adverse event within the two groups during the 6 months of treatment.
- Description of the evolution of functional assessment according to Health Assessment Questionnaire (HAQ) within the two groups during the 6 months of treatment.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
METFORMINE ARROW LAB 500 mg, comprimé pelliculé
PRD2019106 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 1500 mg milligram(s)
- Max total dose
- 1500 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- A10BA02 — METFORMIN
- Marketing authorisation
- NL 36228
- MA holder
- ARROW GENERIQUES
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Removal from the primary packaging and repacking
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- INJECTION
- Route of administration
- INJECTION
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- 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
Auxiliary 2
SCP128175 · ATC
- Active substance
- Calcium Folinate
- Substance synonyms
- LEUCOVORIN CALCIUM
- Route of administration
- ORAL USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B03BB01 — FOLIC ACID
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP107216203 · ATC
- Active substance
- Prednisolone
- Substance synonyms
- (8S,9S,10S,11S,13S,14S,17R)-11,17-DIHYDROXY-17-(2-HYDROXYACETYL)-10,13-DIMETHYL-7,8,9,11,12,14,15,16-OCTAHYDRO-6H-CYCLOPENTA[A]PHENANTHREN-3-ONE, GLPG0303, DELTA-HYDROCORTISONE, 1,2-DEHYDROHYDROCORTISONE, METACORTANDRALONE
- Route of administration
- ORAL USE
- Max daily dose
- 7.5 mg milligram(s)
- Max total dose
- 7.5 mg milligram(s)
- Max treatment duration
- 5 Month(s)
- Authorisation status
- Authorised
- ATC code
- H02AB07 — PREDNISONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Centre Hospitalier Universitaire De Bordeaux
- Sponsor organisation
- Centre Hospitalier Universitaire De Bordeaux
- Address
- 12 Rue Dubernat, Cs 91286 Cs 91286
- City
- Talence
- Postcode
- 33400
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Universitaire De Bordeaux
- Contact name
- Coordinating investigator
Public contact point
- Organisation
- Centre Hospitalier Universitaire De Bordeaux
- Contact name
- Coordinating investigator
Centre Hospitalier Universitaire De Bordeaux
- Sponsor organisation
- Centre Hospitalier Universitaire De Bordeaux
- Address
- 12 Rue Dubernat, Cs 91286 Cs 91286
- City
- Talence
- Postcode
- 33400
- Country
- France
Scientific contact point
- Organisation
- Centre Hospitalier Universitaire De Bordeaux
- Contact name
- Coordinating investigator
Public contact point
- Organisation
- Centre Hospitalier Universitaire De Bordeaux
- Contact name
- Coordinating investigator
Locations
1 EU/EEA country · 10 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruitment ended | 128 | 10 |
| Rest of world | — | 0 | — |
Investigational sites
Centre Hospitalier Universitaire De Bordeaux
Rhumatologie, Place Amelie Raba Leon, 33000, Bordeaux
Centre Hospitalier Universitaire De Toulouse
Rhumatologie, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
Centre Hospitalier Regional Et Universitaire De Brest
Rhumatologie, Boulevard Tanguy Prigent, 29609, Brest Cedex 2
Centre Hospitalier Universitaire De Montpellier
Rhumatologie, 191 Avenue Du Doyen Gaston Giraud, 34295, Montpellier Cedex 5
Centre Hospitalier General De Libourne
Rhumatologie, 112 Rue De La Marne, Bp 199, Libourne Cedex
Centre Hospitalier Regional D'Orleans
Rhumatologie, 14 Avenue De L Hopital, Cs 86709, Orleans Cedex 2
Centre Hospitalier De Pau
Rhumatologie, 4 Boulevard Hauterive, 64000, Pau
Centre Hospitalier De La Cote Basque
Rhumatologie, 13 Avenue Interne Jacques Loeb, 64100, Bayonne
Centre Hospitalier Le Mans
Rhumatologie, 194 Avenue Rubillard, 72037, Le Mans Cedex 9
Ass Hospitaliere Protestante De Lyon
Rhumatologie, 3 Chemin Du Penthod, 69300, Caluire Et Cuire
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 |
|---|---|---|---|---|---|
| France | 2020-12-03 | 2020-12-03 | 2024-06-20 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-06 | France | Acceptable 2024-06-24
|
2024-07-09 |