PhArmaCo-kinetics of InFliximab during treatment Induction

• Register: EUCTR
• Last refreshed on: 29 April 2024
• Main ID: EUCTR2015-004618-10-BE
• Date of registration: 20/11/2015
• Prospective Registration: Yes
• Primary sponsor: CUB- Hopital Erasme
• Public title: PhArmaCo-kinetics of InFliximab during treatment Induction
• Scientific title: Study of the inter-individual variation of PhArmaCo-kinetics of InFliximab during treatment Induction in patients with Crohn’s disease and Ulcerative Colitis
• Date of first enrolment: 19/04/2016
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004618-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Belgium

Contacts

• Name: Liefferinckx
• Affiliation: CUB- Hopital Erasme

• Name: Liefferinckx
• Affiliation: CUB- Hopital Erasme

Key inclusion & exclusion criteria

Inclusion criteria:
Age > 18 years

Moderate-to-severe CD (HBI=8) with endoscopically visible ulcers or moderate-to-severe and severe UC (Mayo Score =6) and Mayo endoscopic subscore >1 (APPENDIX 1-2-3) (a patient with active disease without CRP can be included)

Patients must be starting on infliximab (Remicade (MSD) or CT-P13: Remsima (Mundipharma) or Inflectra (Hospira)) in accordance with national reimbursement criteria or a washout period of 8 weeks will be observed before starting any new anti-TNF therapy after vedolizumab and 4 weeks after adalimumab before starting infliximab

Patients may be naïve to thiopurines or have failed therapy with 1 thiopurine; in which case AZA or 6MP will be either continued or stopped: The dose must remain stable 4 weeks before beginning the study. Patients previously intolerant to Azathioprine or 6-MP can start with the other thiopurine or with Methotrexate (MTX) per investigators discretion. Patient intolerant to standard doses of AZA or 6-MP can start at a lower dose or AZA or 6MP can be stopped per investigators discretion. However, if the immunomodulator is continued or introduced during screening period, the dose should remain stable for the duration of the trial, except if intolerance leading to discontinuation.

Patients failing MTX can continue on MTX with infliximab

Ongoing steroids are allowed if dose was stable 2 weeks before beginning the study with a maximum of prednisone 16 mg/d or budesonide 9 mg/day and should be tapered in 2 weeks.

Patients who consent to receive Infliximab 5 mg/kg at week 0, 2 and 6 and further on every 8 weeks in conjunction with their current Azathioprine, 6-MP or MTX

Women must have a contraceptive method

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
Absence of endoscopically visible ulcers
Ongoing steroid therapy at doses > 16 mg/d prednisolone or equivalent
Ongoing infections
Previous use of IFX
Prior use of biologic therapies excepted if a washout period of 8 weeks is respected
Serious other diseases including cancer in the 5 years prior to inclusion excluding non-melanoma skin cancer
Indication for immediate surgery
Critical gastrointestinal stricture with obstructive symptoms and/or presence of abscess.
Pregnant or breast-feeding woman.
Positive fecal culture for Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium difficile B toxin in the stools
Active tuberculosis. Positive tuberculosis screen per local guidelines
Untreated latent tuberculosis, latent TB is allowed if treated for at least 6 months
Patients with moderate or severe heart failure
Patients with multiple sclerosis or lupus disease
Patients with a history of hypersensitivity to infliximab, or to any of the excipients
HIV, HBV, HCV viral infection (except the presence of positive anti-HBs antibodies) with serology not older than 3 months
Azathioprine or 6-MP in combination with allopurinol or with other myelotoxic therapy (a washout period of 7 days is required for allopurinol or other myelotoxic therapy)
Non-compliant subjects
Participation in another therapeutic study



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

Health Condition(s) or Problem(s) studied

Patients with Crohn disease or Ulcerative Colitis which need biotherapy (antibody against TNF-a)

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Trade Name: Remsima


Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Other descriptive name: Remsima
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: range
Concentration number: 5-10

Trade Name: Remicade
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Other descriptive name: Remicade
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: range
Concentration number: 5-10

Trade Name: Inflectra
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INFLIXIMAB
CAS Number: 170277-31-3
Other descriptive name: Inflectra
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: range
Concentration number: 5-10

Primary Outcome(s)

Main Objective: Evaluation of the inter-individual variability of the pharmacokinetics of infliximab level and antibodies to infliximab during induction treatment and correlation with clinical response at W14 and W30

Primary end point(s): Evaluation of the inter-individual variability of the pharmacokinetics of infliximab level and antibodies to infliximab during induction treatment and correlation with clinical response at W14 and W30

Timepoint(s) of evaluation of this end point: The timepoints of evaluation for the primary endpoint will be done at the end of induction treatment (at 6 weeks)

The correlation between induction treatment and clinical response will be done at W14 and W30

Secondary Objective: Proportion of patients in steroid-free remission at W10-14 w/o normal CRP and/or fecal calprotectin levels

Sustained steroid-free clinical response at W30 w/o normal CRP and/or fecal calprotectin levels and mucosal healing

Sustained steroid-free clinical remission at W30 w/o normal CRP and/or fecal calprotectin levels

Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with clinical response or remission, and/or normal CRP and/or normal fecal calprotectin levels at W14 and 30

Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with sustained IFX levels > 3 µg/ml at W14 and W30 without need for optimization

Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with sustained IFX levels in third and fourth quartile at W14 and W30

Secondary Outcome(s)

Secondary end point(s): Proportion of patients in steroid-free remission at W10-14 w/o normal CRP and/or fecal calprotectin levels

Sustained steroid-free clinical response at W30 w/o normal CRP and/or fecal calprotectin levels and mucosal healing

Sustained steroid-free clinical remission at W30 w/o normal CRP and/or fecal calprotectin levels

Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with clinical response or remission, and/or normal CRP and/or normal fecal calprotectin levels at W14 and 30

Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with sustained IFX levels > 3 µg/ml at W14 and W30 without need for optimization

Correlation of patient population in third and fourth quartile of IFX levels during the induction phase (W0-W10) with sustained IFX levels in third and fourth quartile at W14 and W30

Timepoint(s) of evaluation of this end point: The timepoints of evaluation for the secondary endpoints will be done at:
- W10-14 for the first
- W14 and W30 for the other secondary endpoints

Secondary ID(s)

PACIFIC

Source(s) of Monetary Support

BIRD Group

Ethics review

Status: Approved
Approval date: 19/04/2016
Contact: