Switch between originator infliximab (Remicade®) and biosimilar infliximab (Remsima®) in the treatment of rheumatoid arthritis, spondyloarthritis and chronic inflammatory bowel diseases.

• Register: EUCTR
• Last refreshed on: 7 January 2019
• Main ID: EUCTR2016-002061-54-IT
• Date of registration: 15/11/2018
• Prospective Registration: No
• Primary sponsor: UNIVERSITÀ CATTOLICA DEL SACRO CUORE- POLICLINICO A. GEMELLI
• Public title: Switch between originator infliximab (Remicade®) and biosimilar infliximab (Remsima®) in the treatment of rheumatoid arthritis, spondyloarthritis and chronic inflammatory bowel diseases.
• Scientific title: "Switch between originator infliximab (Remicade®) and biosimilar infliximab (Remsima®) in the treatment of rheumatoid arthritis, spondyloarthritis and chronic inflammatory bowel diseases. Evaluation of immunogenicity and clinical response" - Switch between originator infliximab (Remicade®) and biosimilar infliximab (Remsima®)
• Date of first enrolment: 13/10/2016
• Target sample size: 250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-002061-54
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: Cross over: Other: yes; Other trial design description: single-arm cross over study; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Italy

Contacts

• Name: U.O. Complessa di Reumatologia - Un
• Affiliation: Fondazione Policlinico Universitario "A. Gemelli"

• Name: U.O. Complessa di Reumatologia - Un
• Affiliation: Fondazione Policlinico Universitario "A. Gemelli"

Key inclusion & exclusion criteria

Inclusion criteria:
1. age =18 years
2. diagnosis of
a. Rheumatoid Arthritis according to ACR criteria (1987 e 2010) OR
b. Sieronegative spondiloarthritis (Ankylosing Spondylitis or Sponsiloarthritis (Psoriasic Arthritis) according to ASAS criteria 2009 OR
c. Inflammatory Disease confirmed by endoscopic and histological criteria
3. Treatment with Infliximab RMP (Remicade®) for at least 6 months with stable dosage at least in the last two infusions.
4. Stable clinical response at the time of inclusion in the study (T-1) [stability is defined as reduction =30% of the disease activity scores in comparison with the start of treatment with Infliximab RMP (Remicade®)]
5. In case of concomitant therapy with immunosuppressive drugs (azatioprine/6 mercaptopurine, methotrexate o leflunomide), their dosage should be stable at least in the last 2 months.
6. In case of concomitant systemic therapy with steroids their dosage should be stable at least in the last 2 months and =7.5 mg/die of prednisone (or equivalent)
7. Any concomitant drug for diseases other than those under study should be at a stable dosage for at least 4 weeks before the study inclusion.

Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125

Exclusion criteria:
1. Active Infectious diseases
2. Severe comorbidities (known malignancy except for basal cell carcinoma, congestive heart failure NYHA grade III/IV, liver and/or hepatobiliary disease, renal disease)
3. Pregnancy or breast feeding
4. Any underlying condition which, in the opinion of the Investigator, might contrarindicate the switch to Remsima®



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis, seronegative spondylo arthritis, Crohn's Disease, Ulcerative Colitis
MedDRA version: 20.0 Level: PT Classification code 10002556 Term: Ankylosing spondylitis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
MedDRA version: 20.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders
MedDRA version: 20.0 Level: PT Classification code 10075634 Term: Acute haemorrhagic ulcerative colitis System Organ Class: 10017947 - Gastrointestinal disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: REMSIMA - 100 MG POLVERE PER CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLANCONCINO (VETRO) - 1 FLACONCINO
Product Name: Remsima
Product Code: 42942019
Pharmaceutical Form: Powder for solution for infusion

Primary Outcome(s)

Secondary Objective: The following subpopulations are defined: RA+AS for rheumatic disease, CD+UC for bowel disease.
The objectives are:
To assess the rate of change in the proportion of patients ADA+ before vs after the switch in subpopulations and in the overall study population.
To assess for each pathology the therapeutic equivalence of Infliximab RMP and Infliximab biosimilar, through Clinical Indices and laboratory parameters measured at T-1 and T0 and after the switch at T1, T2 and T3 .
To assess the equivalence of sieric level of ADAs at T0 and T3, in subpopulations and in the overall study population.
To assess the equivalence of sieric level of Infliximab among values measured before vs after the switch.
To assess the safety and tolerability of Infiximab biosimilar with respect to rate of AE and changes in vital signs and hematochemical parameters in subpopulations and in the overall study population.

Main Objective: To demonstrate that the switch from Infliximab RMP (Remicade®) to Infliximab biosimilar (Remsima®), in patients who consent their study participation, does not determine, after 40 weeks of treatment (T3), an increase of the percentage of patients ADA positive= 20% in comparison with that measured at T0.

Primary end point(s): Sieric level of Anti Drug Antibody measured by ELISA test (LISA-TRACKER Duo Infliximab).

Timepoint(s) of evaluation of this end point: T0 (Switch) and T3

Secondary Outcome(s)

Secondary end point(s): Indices of disease activity:
Rheumatoid Arthritis: DAS 28 and CDAI; Spondyloarthritis: BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), ASDAS (Ankylosing Spondylitis Disease Activity Index), LEI (Leeds Enthesitis Index) and only for Psoriatic Arthritis DAPSA (Disease Activity Psoriatic Arthritis), PSAID12 (Psoriatic Arthritis Impact of Disease); Crohn’s Disease: HBI (Harvey Bradshow Index); Ulcerative Colitis pMAYO (partial MAYO).
Indices of quality of life/functional status:
Rheumatoid Arthritis: HAQ (Health Assessment Questionnaire); Spondyloarthritis: BASFI: (Bath Ankylosing Spondylitis Functional Index); Crohn’s Disease and Ulcerative Colitis: IBDQ (Inflammatory Bowel Disease Questionnaire).
Sieric level of infliximab and Anti Drug Antibody measured by ELISA test (LISA-TRACKER Duo Infliximab).

Ematochemical parameters (hemocrome + formula, ERS and CRP, GPT, GGT and GOT, ALP, creatinine only for patients with rheumatological diseases).
Vital signs (blood pressure, body temperature, heart rate)
Physical examination
Adverse events
Anti-Drug Antibodies

Timepoint(s) of evaluation of this end point: T-1, T0 (Switch), T1, T2 and T3

Secondary ID(s)

Re-IMPROVE

Source(s) of Monetary Support

Celltrion Healthcare Co. Ltd