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Trial registered on ANZCTR


Registration number
ACTRN12621001498886
Ethics application status
Approved
Date submitted
23/08/2021
Date registered
4/11/2021
Date last updated
28/01/2024
Date data sharing statement initially provided
4/11/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Switching patients from intravenous to subcutaneous infliximab in inflammatory bowel disease
Scientific title
Comparison between switching from intravenous to subcutaneous infliximab on the maintenance of clinical and biochemical remission in patients with inflammatory bowel disease
Secondary ID [1] 305114 0
None
Universal Trial Number (UTN)
Trial acronym
SISS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative colitis 323334 0
Crohn's disease 323336 0
Condition category
Condition code
Inflammatory and Immune System 320901 320901 0 0
Autoimmune diseases
Oral and Gastrointestinal 320902 320902 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention - switching patients from intravenous infliximab to subcutaneous infliximab for the treatment of inflammatory bowel disease
- subcutaneous infliximab: administered via a pre-filled syringe at a dose of 120mg subcutaneously every 2 weeks
- total duration: 48 weeks
- adherence monitored by: initial supervision by subcutaneous infliximab nurse, and infliximab levels completed at week 24 and 48.
Intervention code [1] 321504 0
Treatment: Drugs
Comparator / control treatment
Control - continuing intravenous infliximab for the treatment of inflammatory bowel disease
- intravenous infliximab: administered at a dose of 5mg/kg every 8 weeks for a duration of 48 weeks
- adherence: attendance at infusion sessions, infliximab levels at week 24 and 48
Control group
Active

Outcomes
Primary outcome [1] 328690 0
Composite primary outcome: Comparing the proportion of patients who remain in clinical remission [defined as partial Mayo score < 2 (for ulcerative colitis in SISS 1) or Harvey Bradshaw Index < 5 (for Crohn’s disease in SISS 2) and biochemical remission [defined as C-reactive protein < 5 mg/L and/or faecal calprotectin < 150 µg/mL] in the intravenous (IV) infliximab group versus the subcutaneous (SC) infliximab group at week 48, AND having not met any of the following treatment endpoints:
o Need for corticosteroids
o Adding immunomodulator
o Need for dose-escalation of infliximab
o Switching to another biological agent
o Need for IBD surgery

Method of assessment:
- partial Mayo score or Harvey Bradshaw index: taking a history from the patient about symptoms
- C-reactive protein: blood sample
- Faecal calprotectin: stool sample
- Need for corticosteroids/adding immunomodulator/need for dose-escalation of infliximab/switching to another biological agent/need for IBD surgery: accessing patient medical record
Timepoint [1] 328690 0
48 weeks post-intervention commencement
Secondary outcome [1] 399967 0
Comparing the change in infliximab trough level in the IV infliximab group versus the SC infliximab group using a blood sample
Timepoint [1] 399967 0
Week 24 and 48 post-intervention commencement
Secondary outcome [2] 399968 0
Patient satisfaction in the SC infliximab group using a survey with a 5-point Likert scale
Timepoint [2] 399968 0
48 weeks post-intervention commencement
Secondary outcome [3] 399969 0
Comparing the change in faecal calprotectin in the IV infliximab group versus the SC infliximab group using stool samples
Timepoint [3] 399969 0
Week 24 and 48 post-intervention commencement
Secondary outcome [4] 399970 0
Comparing the change in medical therapy between the IV infliximab and SC infliximab group (using data-linkage to medical records):
o Need for corticosteroids
Timepoint [4] 399970 0
week 48 post-intervention commencement
Secondary outcome [5] 399971 0
Comparing other standard of care biochemical monitoring of patients on infliximab using a blood sample
o FBC, EUC, LFT, CRP, ESR
Timepoint [5] 399971 0
week 24 and 48 post-intervention commencement
Secondary outcome [6] 399972 0
Pharmacovigilance of potential treatment-associated adverse effects, assessed in accordance with the Common Terminology Criteria for Adverse Events
Timepoint [6] 399972 0
week 48 post-intervention commencement
Secondary outcome [7] 401407 0
Comparing the change in medical therapy between the IV infliximab and SC infliximab group (using data linkage to medical records):
o Adding immunomodulator
Timepoint [7] 401407 0
48 weeks post-intervention commencement
Secondary outcome [8] 401408 0
Comparing the change in medical therapy between the IV infliximab and SC infliximab group (using data-linkage to medical records):
o Need for dose-escalation
Timepoint [8] 401408 0
48 weeks post-intervention commencement
Secondary outcome [9] 401409 0
Comparing the change in medical therapy between the IV infliximab and SC infliximab group (using data-linkage to medical records):
o Switching to another biological agent
Timepoint [9] 401409 0
48 weeks post-intervention commencement
Secondary outcome [10] 401410 0
Comparing the change in medical therapy between the IV infliximab and SC infliximab group (using data-linkage to medical records):
o Need for IBD surgery
Timepoint [10] 401410 0
48 weeks post-intervention commencement
Secondary outcome [11] 402182 0
Comparing the change in infliximab antibodies in the IV infliximab group versus the SC infliximab group using a blood sample
Timepoint [11] 402182 0
Week 24 and 48 post-intervention commencement

Eligibility
Key inclusion criteria
·Diagnosis of ulcerative colitis or Crohn's disease
·On IV infliximab treatment – must be on maintenance treatment at 5mg/kg dosing every 8 weeks
·Steroids-free clinical remission and/or biochemical remission for at least 12 weeks
a. Clinical remission:
i. Ulcerative colitis: Partial Mayo Score (pMS) < 2
ii. Crohn's disease: Harvey Bradshaw Index (HBI) < 5 points
b. Biochemical remission:
i. C-reactive protein (CRP) < 5mg/L
ii. Faecal calprotectin < 150 µg/mL
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Age < 18 years
- Patients awaiting bowel surgery
- Patients with a stoma
- Consent not obtained or unable to give informed consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
SISS 1: for patients with ulcerative colitis

SISS 2: for patients with Crohn's disease
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
SISS 1 - ulcerative colitis
The study is designed as a non-inferiority study and statistically powered based on the best available data. Analyses will be based on intention to treat. Assuming no difference between the IV and SC arms in the proportions of patients reaching the primary outcome, we estimate that 66 patients (33 per group) were required to ensure 80% power with alpha value of 0.05 where the non-inferiority margin is 15% This is based upon the best available data with an expected clinical remission rate of 53.8% in the IV group versus 68.4% in the SC group at week 48.

SISS 2: Crohn's disease
The study is designed as a non-inferiority study and statistically powered based on the best available data. Analyses will be based on intention to treat. Assuming no difference between the IV and SC arms in the proportions of patients reaching the primary outcome, we estimate that 110 patients (55 per group) were required to ensure 80% power with alpha value of 0.05 where the non-inferiority margin is 15 percentage points. This is based upon the best available data with an expected clinical remission rate of 56.0% in the IV group versus 64.3% in the SC group at week 48.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/10/2021
Date of last participant enrolment
Anticipated
1/04/2024
Actual
Date of last data collection
Anticipated
1/03/2025
Actual
Sample size
Target
176
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 20312 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 20313 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 20314 0
Blacktown Hospital - Blacktown
Recruitment hospital [4] 20315 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [5] 20316 0
St George Hospital - Kogarah
Recruitment hospital [6] 20317 0
Mater Private Hospital - South Brisbane
Recruitment hospital [7] 20318 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [8] 20319 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [9] 26085 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [10] 26086 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [11] 26087 0
John Hunter Hospital - New Lambton
Recruitment hospital [12] 26088 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [13] 26089 0
Westmead Hospital - Westmead
Recruitment hospital [14] 26090 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [15] 26091 0
Wollongong Hospital - Wollongong
Recruitment hospital [16] 26092 0
Logan Hospital - Meadowbrook
Recruitment hospital [17] 26093 0
Royal Perth Hospital - Perth
Recruitment hospital [18] 26094 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [19] 26095 0
Macquarie University - North Ryde
Recruitment hospital [20] 26096 0
Coral Sea Clinical Research Unit - North Mackay
Recruitment hospital [21] 26097 0
The Prince Charles Hospital - Chermside
Recruitment hospital [22] 26098 0
The Northern Hospital - Epping
Recruitment postcode(s) [1] 35054 0
2139 - Concord
Recruitment postcode(s) [2] 35055 0
2170 - Liverpool
Recruitment postcode(s) [3] 35056 0
2148 - Blacktown
Recruitment postcode(s) [4] 35057 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 35058 0
2217 - Kogarah
Recruitment postcode(s) [6] 35059 0
4101 - South Brisbane
Recruitment postcode(s) [7] 35060 0
6150 - Murdoch
Recruitment postcode(s) [8] 35061 0
2050 - Camperdown
Recruitment postcode(s) [9] 41940 0
3065 - Fitzroy
Recruitment postcode(s) [10] 41941 0
3050 - Parkville
Recruitment postcode(s) [11] 41942 0
2305 - New Lambton
Recruitment postcode(s) [12] 41943 0
2298 - Waratah
Recruitment postcode(s) [13] 41944 0
2145 - Westmead
Recruitment postcode(s) [14] 41945 0
3084 - Heidelberg
Recruitment postcode(s) [15] 41946 0
2500 - Wollongong
Recruitment postcode(s) [16] 41947 0
4131 - Meadowbrook
Recruitment postcode(s) [17] 41948 0
6000 - Perth
Recruitment postcode(s) [18] 41949 0
5011 - Woodville
Recruitment postcode(s) [19] 41950 0
2109 - North Ryde
Recruitment postcode(s) [20] 41951 0
4740 - North Mackay
Recruitment postcode(s) [21] 41952 0
4032 - Chermside
Recruitment postcode(s) [22] 41953 0
3076 - Epping

Funding & Sponsors
Funding source category [1] 309503 0
Commercial sector/Industry
Name [1] 309503 0
Celltrion Healthcare Australia Pty Ltd
Country [1] 309503 0
Australia
Primary sponsor type
Hospital
Name
Concord Repatriation General Hospital
Address
Department of Gastroenterology
Level 1 West
Concord Hospital
Hospital Rd
Concord, NSW 2139
Country
Australia
Secondary sponsor category [1] 310484 0
None
Name [1] 310484 0
Address [1] 310484 0
Country [1] 310484 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309289 0
Sydney Local Health District Human Research Ethics Committee CRGH
Ethics committee address [1] 309289 0
Concord Hospital
Building 20, Ground Floor, Hospital Road,
Concord NSW 2139
Ethics committee country [1] 309289 0
Australia
Date submitted for ethics approval [1] 309289 0
13/06/2021
Approval date [1] 309289 0
16/08/2021
Ethics approval number [1] 309289 0
CH62/6/2021-094

Summary
Brief summary
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal system that mainly comprises ulcerative colitis (UC) and Crohn’s disease (CD). Treatment modalities include anti-tumour necrosis factor (TNF) biological agents such as intravenous (IV) infliximab infusions given regularly every 8 weeks, subcutaneous (SC) adalimumab given every 2 weeks and golimumab given every 4 weeks. Anti-TNF drugs are now available as biosimilars, which are identical copies of the originator drug.

Remsima® is prescribed for adults 18 years or older at a dose of 120mg infliximab solution SC via pre-filled syringe or pen every 2 weeks. The efficacy of SC infliximab is similar to IV infliximab at one year in an initial open-label study. Another study demonstrated non-inferiority of SC infliximab compared with IV infliximab in terms of pharmacokinetic, efficacy and safety in patients with active Crohn’s disease and ulcerative colitis. Efficacy analysis found no statistically significant differences between both routes of administration. Safety profile was also comparable between both groups.

The aim of our study is to determine whether SC infliximab is non-inferior to IV infliximab in the maintenance of clinical and biochemical remission in patients in IBD within Australia.. This study differs from prior studies as we will examine patients in remission (and not those with active disease). We also aim to determine the patient satisfaction of switching from IV infliximab to SC infliximab as determined by a self-administered questionnaire.

The hypothesis of this study is that there is no difference in clinical outcomes between the two groups and that patients will be more satisfied with SC infliximab.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113642 0
Prof Rupert Leong
Address 113642 0
Level 1 West,
Concord Repatriation General Hospital
Hospital Rd
Concord, NSW 2139
Country 113642 0
Australia
Phone 113642 0
+61 02 97675548
Fax 113642 0
Email 113642 0
[email protected]
Contact person for public queries
Name 113643 0
Prof Rupert Leong
Address 113643 0
Level 1 West,
Concord Repatriation General Hospital
Hospital Rd
Concord, NSW 2139
Country 113643 0
Australia
Phone 113643 0
+61 02 97675548
Fax 113643 0
Email 113643 0
[email protected]
Contact person for scientific queries
Name 113644 0
Prof Rupert Leong
Address 113644 0
Level 1 West,
Concord Repatriation General Hospital
Hospital Rd
Concord, NSW 2139
Country 113644 0
Australia
Phone 113644 0
+61 02 97675548
Fax 113644 0
Email 113644 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIReal-world experience with subcutaneous infliximab: broadening treatment strategies for inflammatory bowel disease2023https://doi.org/10.1080/1744666x.2023.2231148
N.B. These documents automatically identified may not have been verified by the study sponsor.