Stepwise extention of the adalimumab injection interval in patients with stable Crohn's disease.

• Register: EUCTR
• Last refreshed on: 10 April 2017
• Main ID: EUCTR2016-003321-42-NL
• Date of registration: 08/12/2016
• Prospective Registration: Yes
• Primary sponsor: Radboud University Medical Centre
• Public title: Stepwise extention of the adalimumab injection interval in patients with stable Crohn's disease.
• Scientific title: Lengthening Adalimumab Dosing Interval in quiescent Crohn’s disease patients: the LADI study.
• Date of first enrolment: 18/01/2017
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003321-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Netherlands

Contacts

• Name: Frank Hoentjen
• Affiliation: Radboudumc

• Name: Frank Hoentjen
• Affiliation: Radboudumc

Key inclusion & exclusion criteria

Inclusion criteria:
• Age 18 or older
• Diagnosis of colonic and/or distal ileal CD
• Sustained steroid-free clinical remission for >12 months whilst being treated with adalimumab at a stable dose
• Adalimumab dosed at 40 mg every 2 weeks
• Full clinical response and disease control, all three criteria below need to be fulfilled prior to enrollment:
- Absence of active inflammatory intestinal or extra-intestinal symptoms, as judged by both patient and physician
- Fecal calprotectin (FC) < 150 µg/g and CRP <5 mg/L
- Harvey Bradshaw Index (HBI) <5

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 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 34

Exclusion criteria:
• Absence of written informed consent
• Concomitant corticosteroid usage
• Need for IBD-related surgery
• Actively draining peri-anal fistula
• Pregnancy or lactation
• Other significant medical conditions that might interfere with this study (such as current/recent malignancy, immunodeficiency syndromes and psychiatric illness)
• Impossibility to measure outcomes, e.g. planned relocation, language issues, short life expectancy



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

Health Condition(s) or Problem(s) studied

Crohn's disease

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

Intervention(s)

Trade Name: Humira (adalimumab)
Product Name: Adalimumab
Pharmaceutical Form: Injection
INN or Proposed INN: ADALIMUMAB
CAS Number: 331731-18-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 48 weeks

Primary end point(s): Difference in cumulative incidence of persistent exacerbations (>8 weeks) between the dose reduction and usual care groups at 48-week follow-up.

Main Objective: Key objective of this study is to demonstrate non-inferiority of disease activity guided adalimumab injection interval lengthening compared to usual care (continued dosing) in maintaining remission in CD at 48 weeks of follow-up.

Secondary Objective: - The proportion of patients in remission with interval extension at 48 weeks.
- The proportion of persistent flares (persistent flare is defined as >8 weeks HBI increase = 5, FC >250 µg/g and/or CRP >5 mg/L) between the interval extension and usual care groups.
- To compare quality of life maintenance between interval extension and usual care groups.
- To compare disease activity (HBI) every 3 months during the follow-up of 48 weeks between interval extension and usual care.
- To identify factors, which are linked to successful interval extension (e.g. baseline patient and treatment characteristics, FC, CRP, adalimumab trough levels and antibodies to adalimumab).
- To compare development of serious adverse events (SAEs) between interval extension and usual care.

Secondary Outcome(s)

Secondary end point(s): • Cumulative incidence of patients with transient flare (duration =8 weeks)
• Disease activity measured by Harvey-Bradshaw Index (HBI) and fecal calprotectin (FC)
• PROM: PRO-2 (abdominal pain and stool frequency).
• Adalimumab trough levels
• Anti-adalimumab antibody levels
• Adverse event rates (including injection site reactions and infections)
• Quality of life (via SIBDQ)
• Costs from a health care and societal perspective (via EQ-5D-5L, iMTA PCQ and iMTA MCQ)
- (S)AE's

Timepoint(s) of evaluation of this end point: Patients will be seen every 3 months.

Secondary ID(s)

84801 5002

NL58948.091.16

Source(s) of Monetary Support

Radboudumc