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

Tracking Information

• First Submitted Date: May 23, 2014
• First Posted Date: May 28, 2014
• Last Update Posted Date: September 25, 2017
• Study Start Date: October 2014
• Actual Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 27, 2014)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 17, 2016)

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

• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: June 17, 2016)

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

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The NOR-SWITCH Study
• 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
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Rheumatoid Arthritis
• Spondyloarthritis
• Psoriatic Arthritis
• Ulcerative Colitis
• Crohn's Disease
• Psoriasis Chronic

Intervention

• Drug: Innovator infliximab
  Other Name: Remicade
• Drug: Biosimilar infliximab
  Other Name: Remsima

Study Arms

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

Publications *

• Jørgensen KK, Goll GL, Sexton J, Bolstad N, Olsen IC, Asak Ø, 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, Prestegård U, Rydning JH, Sagatun L, Seeberg KA, Torp R, Vold C, Warren DJ, Ystrøm 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, Jørgensen 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 Ø, Baigh S, Blomgren IM, Brenna Ø, 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, Prestegård U, Rashid HU, Strand EK, Skjetne K, Seeberg KA, Torp R, Ystrøm CM, Vold C, Zettel CC, Waksvik K, Gulbrandsen B, Hagfors J, Mørk 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.
• Jørgensen KK, Olsen IC, Goll GL, Lorentzen M, Bolstad N, Haavardsholm EA, Lundin KEA, Mørk 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 6, 2016): 482
• Original Estimated Enrollment (submitted: May 27, 2014): 500
• Actual Study Completion Date: January 2017
• Actual Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Norway

Administrative Information

• NCT Number: NCT02148640
• Other Study ID Numbers: DIA2014-01; 2014-002056-40 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Tore K Kvien, Diakonhjemmet Hospital
• Study Sponsor: Diakonhjemmet Hospital
• Collaborators: South-Eastern Norway Regional Health Authority

Investigators

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

• PRS Account: Diakonhjemmet Hospital
• Verification Date: September 2017