The NOR-SWITCH Study (NOR-SWITCH)

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

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

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Crohn's Disease; Ulcerative Colitis; Psoriatic Arthritis; Spondyloarthritis; Psoriasis Chronic
• Intervention / Treatment: Drug: Biosimilar infliximab; Drug: Innovator infliximab

• Study Type: Interventional
• Enrollment (Actual): 482
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Arendal, Norway
    • Sørlandet Sykehus HF
  • Bergen, Norway
    • Haukeland Universitetssykehus
  • Bergen, Norway
    • Haukeland Universitetssjukehus Hf
  • Bodø, Norway
    • Nordlandssykehuset
  • Elverum, Norway
    • Sykehuset Innlandet
  • Fredrikstad, Norway
    • Sykehuset Østfold HF
  • Førde, Norway
    • Helse Førde HF
  • Gjettum, Norway
    • Bærum sykehus
  • Gjøvik, Norway
    • Sykehuset Innlandet
  • Hamar, Norway
    • Sykehuset Innlandet
  • Haugesund, Norway
    • Haugesund sanitetsforenings revmatismesykehus
  • Haugesund, Norway
    • Helse Fonna HF
  • Kristiansand, Norway
    • Sørlandet Sykehus HF
  • Levanger, Norway
    • Helse Nord-Trøndelag
  • Lillehammer, Norway
    • Revmatismesykehuset Lillehammer
  • Lillehammer, Norway
    • Sykehuset Innlandet
  • Lørenskog, Norway
    • Akershus Universitetssykehus
  • Mo i Rana, Norway
    • Helgelandssykehuset
  • Oslo, Norway, 0319
    • Department of Rheumatology, Diakonhjemmet Hospital
  • Oslo, Norway
    • Diakonhjemmet Hospital
  • Oslo, Norway
    • Oslo Universitetssykehus, Rikshospitalet
  • Oslo, Norway
    • Oslo universitetssykehus, Ullevål
  • Sandvika, Norway
    • Martina Hansens Hospital
  • Skien, Norway
    • Sykehuset Telemark HF
  • Skien, Norway
    • Betanien Hospital
  • Tromsø, Norway
    • Universitetssykehuset i Nord-Norge
  • Trondheim, Norway
    • St. Olavs Hospital
  • Trondheim, Norway
    • St. Olavs hospital HF
  • Tønsberg, Norway
    • Sykehuset Vestfold
  • Ålesund, Norway
    • Ålesund Sjukehus, Helse Møre og Romsdal HF

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Remsima
Active Comparator: INX; Continued infusions of innovator infliximab (Remicade) with same dose and frequency as prior to inclusion	Drug: Innovator infliximab; Other Names: Remicade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of disease worsening	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.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to disease worsening		52 weeks
Occurrence of study drug discontinuation		52 weeks
Time to study drug discontinuation		52 weeks
Patient's global assessment of disease activity		52 weeks
Physicians's global assessment of disease activity		52 weeks
Inflammation laboratory parameters	ESR and CRP for all patients, Calprotectin for UC and CD patients	52 weeks
Remission status according to DAS28	For RA and PsA patients	52 weeks
Disease activity according to DAS28	For RA and PsA patients	52 weeks
Remission status according to CDAI	For RA and PsA patients	52 weeks
Disease activity according to CDAI	For RA and PsA patients	52 weeks
Remission status according to SDAI	For RA and PsA patients	52 weeks
Disease activity according to SDAI	For RA and PsA patients	52 weeks
Remission status according to ACR/EULAR	For RA and PsA patients	52 weeks
Disease activity according to ACR/EULAR	For RA and PsA patients	52 weeks
Remission status according to ASDAS	For SpA patients	52 weeks
Disease activity according to ASDAS	For SpA patients	52 weeks
Remission status according to Partial Mayo Score	For UC patients	52 weeks
Disease activity according to Partial Mayo Score	For UC patients	52 weeks
Remission status according to Harvey-Bradshaw index	For CD patients	52 weeks
Disease activity according to Harvey-Bradshaw index	For CD patients	52 weeks
Remission status according to PASI	For psoriatic patients	52 weeks
Disease activity according to PASI	For psoriatic patients	52 weeks

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Diakonhjemmet Hospital
• Collaborators: South-Eastern Norway Regional Health Authority
• Investigators: Principal Investigator: Tore K. Kvien, MD PhD, Diakonhjemmet Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: May 23, 2014
• First Submitted That Met QC Criteria: May 27, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Actual): September 25, 2017
• Last Update Submitted That Met QC Criteria: September 22, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Skin Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Gastrointestinal Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Inflammatory Bowel Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ulcer; Arthritis; Arthritis, Rheumatoid; Psoriasis; Crohn Disease; Arthritis, Psoriatic; Colitis; Colitis, Ulcerative; Spondylitis; Spondylarthritis; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: DIA2014-01; 2014-002056-40 (EudraCT Number)