The NOR-SWITCH Study (NOR-SWITCH)

• ClinicalTrials.gov Identifier: NCT02148640
• Recruitment Status: Completed
• First Posted: May 28, 2014
• Last Update Posted: September 25, 2017
• Sponsor: Diakonhjemmet Hospital
• Collaborator: South-Eastern Norway Regional Health Authority
• Information provided by (Responsible Party): Tore K Kvien, Diakonhjemmet Hospital

Study Description

Brief Summary:

The purpose of this study is to assess the safety and efficacy of switching from Remicade to the biosimilar treatment Remsima in patients with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn's disease and chronic plaque psoriasis

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis; Spondyloarthritis; Psoriatic Arthritis; Ulcerative Colitis; Crohn's Disease; Psoriasis Chronic	Drug: Innovator infliximab; Drug: Biosimilar infliximab	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 482 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP STUDY TO EVALUATE THE SAFETY AND EFFICACY OF SWITCHING FROM INNOVATOR INFLIXIMAB TO BIOSIMILAR INFLIXIMAB COMPARED WITH CONTINUED TREATMENT WITH INNOVATOR INFLIXIMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS, SPONDYLOARTHRITIS, PSORIATIC ARTHRITIS, ULCERATIVE COLITIS, CROHN'S DISEASE AND CHRONIC PLAQUE PSORIASIS THE NOR-SWITCH STUDY
• Study Start Date: October 2014
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: January 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: CT-P13; Infusions of biosimilar infliximab (Remsima) with same dose and frequency as pre-inclusion treatment with innovator infliximab (Remicade)	Drug: Biosimilar infliximab; Other Name: Remsima
Active Comparator: INX; Continued infusions of innovator infliximab (Remicade) with same dose and frequency as prior to inclusion	Drug: Innovator infliximab; Other Name: Remicade

Outcome Measures

Primary Outcome Measures :

1. Occurrence of disease worsening [ Time Frame: 52 weeks ]

   A disease worsening in RA and PsA is defined as an increase in DAS28 of ≥ 1.2 from randomization and a minimum DAS score of 3.2.

   A disease worsening in AS/SpA is defined as an increase in ASDAS of ≥1.1 from randomization and a minimum ASDAS of 2.1.

   A disease worsening in ulcerative colitis is defined as an increase in Partial Mayo score of ≥ 3 points from randomization and a minimum partial Mayo score of ≥ 5 points.

   A disease worsening in Crohn's disease is defined as an increase in HBI of ≥ 4 points from randomization and a minimum HBI score of 7 points.

   A disease worsening in psoriasis is defined as an increase in PASI of ≥ 3 points from randomization and a minimum PASI score of 5.

   If a patient does not fulfill the formal definition, but experiences a clinically significant worsening according to both the investigator and patient and which leads to a major change in treatment this should be considered as a disease worsening but recorded separately in the CRF.

Secondary Outcome Measures :

1. Time to disease worsening [ Time Frame: 52 weeks ]
2. Occurrence of study drug discontinuation [ Time Frame: 52 weeks ]
3. Time to study drug discontinuation [ Time Frame: 52 weeks ]
4. Patient's global assessment of disease activity [ Time Frame: 52 weeks ]
5. Physicians's global assessment of disease activity [ Time Frame: 52 weeks ]
6. Inflammation laboratory parameters [ Time Frame: 52 weeks ]
   ESR and CRP for all patients, Calprotectin for UC and CD patients
7. Remission status according to DAS28 [ Time Frame: 52 weeks ]
   For RA and PsA patients
8. Disease activity according to DAS28 [ Time Frame: 52 weeks ]
   For RA and PsA patients
9. Remission status according to CDAI [ Time Frame: 52 weeks ]
   For RA and PsA patients
10. Disease activity according to CDAI [ Time Frame: 52 weeks ]
    For RA and PsA patients
11. Remission status according to SDAI [ Time Frame: 52 weeks ]
    For RA and PsA patients
12. Disease activity according to SDAI [ Time Frame: 52 weeks ]
    For RA and PsA patients
13. Remission status according to ACR/EULAR [ Time Frame: 52 weeks ]
    For RA and PsA patients
14. Disease activity according to ACR/EULAR [ Time Frame: 52 weeks ]
    For RA and PsA patients
15. Remission status according to ASDAS [ Time Frame: 52 weeks ]
    For SpA patients
16. Disease activity according to ASDAS [ Time Frame: 52 weeks ]
    For SpA patients
17. Remission status according to Partial Mayo Score [ Time Frame: 52 weeks ]
    For UC patients
18. Disease activity according to Partial Mayo Score [ Time Frame: 52 weeks ]
    For UC patients
19. Remission status according to Harvey-Bradshaw index [ Time Frame: 52 weeks ]
    For CD patients
20. Disease activity according to Harvey-Bradshaw index [ Time Frame: 52 weeks ]
    For CD patients
21. Remission status according to PASI [ Time Frame: 52 weeks ]
    For psoriatic patients
22. Disease activity according to PASI [ Time Frame: 52 weeks ]
    For psoriatic patients

Other Outcome Measures:

1. RAND SF-36 [ Time Frame: 52 weeks ]
2. Modified Health Assessment Questionnaire (MHAQ) [ Time Frame: 52 weeks ]
   Only RA, SpA and PsA patients
3. Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: 52 weeks ]
   Only UC and CD patients
4. Dermatology Life Quality Index (DLQI) [ Time Frame: 52 weeks ]
   Only Ps patients
5. EQ-5D [ Time Frame: 52 weeks ]
6. RAID [ Time Frame: 52 weeks ]
   Only RA patients
7. PsAID [ Time Frame: 52 weeks ]
   Only PsA patients
8. WPAI:GH [ Time Frame: 52 weeks ]
   Work Productivity and Activity Impairment Questionnaire: General health
9. Safety and tolerability: AEs, laboratory parameters [ Time Frame: through study completion, an average of 52 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. A clinical diagnosis of either rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis, Crohn's disease or chronic plaque psoriasis
2. Male or non-pregnant, non-nursing female
3. >18 years of age at screening
4. Stable treatment with innovator infliximab (Remicade) during the last 6 months
5. Subject capable of understanding and signing an informed consent form
6. Provision of written informed consent

Exclusion Criteria:

1. Major co-morbidities, such as severe malignancies, severe diabetic mellitus, severe infections, uncontrollable hypertension, severe cardiovascular disease (NYHA class 3 or 4) and/or severe respiratory diseases

2. Change of major co-medication during the last 2 months prior to randomization:

   RA, SpA and PsA: Initiation of systemic corticosteroids or synthetic DMARDs or other medication which according to the investigator would interfere with the stability of the disease.

   UC and CD: Initiation of systemic corticosteroids or an immunosuppressant or other medication which according to the investigator would interfere with the stability of the disease Psoriasis: Initiation of synthetic DMARDs or other medication which according to the investigator would interfere with the stability of the disease

3. Inadequate birth control, pregnancy, and/or breastfeeding
4. Psychiatric or mental disorders, alcohol abuse or other substance abuse, language barriers or other factors which makes adherence to the study protocol impossible
5. Change in treatment with innovator infliximab (Remicade) during the last 6 months due to disease related factors, not including dose/frequency adjustments due to drug concentration measurements

Contacts and Locations

Locations

Norway

Sørlandet Sykehus HF

Arendal, Norway

Haukeland Universitetssjukehus Hf

Bergen, Norway

Haukeland Universitetssykehus

Bergen, Norway

Nordlandssykehuset

Bodø, Norway

Sykehuset Innlandet

Elverum, Norway

Sykehuset Østfold HF

Fredrikstad, Norway

Helse Førde Hf

Førde, Norway

Bærum Sykehus

Gjettum, Norway

Sykehuset Innlandet

Gjøvik, Norway

Sykehuset Innlandet

Hamar, Norway

Haugesund Sanitetsforenings Revmatismesykehus

Haugesund, Norway

Helse Fonna HF

Haugesund, Norway

Sørlandet Sykehus HF

Kristiansand, Norway

Helse Nord-Trøndelag

Levanger, Norway

Revmatismesykehuset Lillehammer

Lillehammer, Norway

Sykehuset Innlandet

Lillehammer, Norway

Akershus Universitetssykehus

Lørenskog, Norway

Helgelandssykehuset

Mo i Rana, Norway

Department of Rheumatology, Diakonhjemmet Hospital

Oslo, Norway, 0319

Diakonhjemmet Hospital

Oslo, Norway

Oslo Universitetssykehus, Rikshospitalet

Oslo, Norway

Oslo Universitetssykehus, Ullevål

Oslo, Norway

Martina Hansens Hospital

Sandvika, Norway

Betanien Hospital

Skien, Norway

Sykehuset Telemark HF

Skien, Norway

Universitetssykehuset i Nord-Norge

Tromsø, Norway

St. Olavs Hospital HF

Trondheim, Norway

St. Olavs Hospital

Trondheim, Norway

Sykehuset Vestfold

Tønsberg, Norway

Ålesund Sjukehus, Helse Møre og Romsdal HF

Ålesund, Norway

Sponsors and Collaborators

Diakonhjemmet Hospital

South-Eastern Norway Regional Health Authority

Investigators

• Principal Investigator: Tore K. Kvien, MD PhD; Diakonhjemmet Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jorgensen KK, Goll GL, Sexton J, Bolstad N, Olsen IC, Asak O, Berset IP, Blomgren IM, Dvergsnes K, Florholmen J, Frigstad SO, Henriksen M, Hagfors J, Huppertz-Hauss G, Haavardsholm EA, Klaasen RA, Moum B, Noraberg G, Prestegard U, Rydning JH, Sagatun L, Seeberg KA, Torp R, Vold C, Warren DJ, Ystrom CM, Lundin KEA, Kvien T, Jahnsen J. Efficacy and Safety of CT-P13 in Inflammatory Bowel Disease after Switching from Originator Infliximab: Exploratory Analyses from the NOR-SWITCH Main and Extension Trials. BioDrugs. 2020 Oct;34(5):681-694. doi: 10.1007/s40259-020-00438-7.

Goll GL, Jorgensen KK, Sexton J, Olsen IC, Bolstad N, Haavardsholm EA, Lundin KEA, Tveit KS, Lorentzen M, Berset IP, Fevang BTS, Kalstad S, Ryggen K, Warren DJ, Klaasen RA, Asak O, Baigh S, Blomgren IM, Brenna O, Bruun TJ, Dvergsnes K, Frigstad SO, Hansen IM, Hatten ISH, Huppertz-Hauss G, Henriksen M, Hoie SS, Krogh J, Midtgard IP, Mielnik P, Moum B, Noraberg G, Poyan A, Prestegard U, Rashid HU, Strand EK, Skjetne K, Seeberg KA, Torp R, Ystrom CM, Vold C, Zettel CC, Waksvik K, Gulbrandsen B, Hagfors J, Mork C, Jahnsen J, Kvien TK. Long-term efficacy and safety of biosimilar infliximab (CT-P13) after switching from originator infliximab: open-label extension of the NOR-SWITCH trial. J Intern Med. 2019 Jun;285(6):653-669. doi: 10.1111/joim.12880. Epub 2019 Apr 12.

Jorgensen KK, Olsen IC, Goll GL, Lorentzen M, Bolstad N, Haavardsholm EA, Lundin KEA, Mork C, Jahnsen J, Kvien TK; NOR-SWITCH study group. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet. 2017 Jun 10;389(10086):2304-2316. doi: 10.1016/S0140-6736(17)30068-5. Epub 2017 May 11. Erratum In: Lancet. 2017 Jun 10;389(10086):2286.

• Responsible Party: Tore K Kvien, Prof. Dr. Med., Diakonhjemmet Hospital
• ClinicalTrials.gov Identifier: NCT02148640
• Other Study ID Numbers: DIA2014-01; 2014-002056-40 ( EudraCT Number )
• First Posted: May 28, 2014
• Last Update Posted: September 25, 2017
• Last Verified: September 2017

Additional relevant MeSH terms:

Spondylitis; Arthritis; Arthritis, Rheumatoid; Arthritis, Psoriatic; Spondylarthritis; Crohn Disease; Colitis; Colitis, Ulcerative; Psoriasis; Ulcer; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Skin Diseases, Papulosquamous; Skin Diseases; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colonic Diseases; Pathologic Processes; Spondylarthropathies; Spinal Diseases; Bone Diseases; Bone Diseases, Infectious; Infections