Colitis
Conditions
Brief summary
GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis (GOAL-ARC). A nationwide multi-centred randomised controlled trial (RCT) investigating the use of GLM dose adjustment in ulcerative colitis (UC). The primary objective is to ascertain if dose adjustment of GLM based on GLM drug levels and FCP levels results in higher response and remission rates than standard SmPC dosing.
Detailed description
UC is a chronic inflammatory bowel disease (IBD) in which the lining of the large intestine become inflamed. There is no official database which gives accurate figures but it is thought that at least 20,000 people are living with IBD in Ireland. Males and females are affected equally and patients can be diagnosed at any age, including babies and children. The peak age of incidence is between the ages of 15 and 35, with a second (smaller) peak from the 50s to 70s. GLM is a human IgG1κ monoclonal antibody produced by a murine hybridoma cell line with recombinant DNA technology. It is part of the immunosuppressants pharmacotherapeutic group of TNF-α inhibitors. It is licensed for use in several chronic inflammatory conditions including UC, Psoriatic arthritis, axial spondylitis, rheumatoid arthritis. The design of GOAL-ARC aims to address the impact of dose escalation of GLM immediately following induction and during the subsequent maintenance phase in response to suboptimal drugs levels or persisting inflammatory burden as represented by raised faecal calprotectin (FCP). FCP has been shown to correlate closely to endoscopic disease activity6.
Interventions
DRUGGolimumab (GLM)
GLM is a human IgG1κ monoclonal antibody produced by a murine hybridoma cell line with recombinant DNA technology
Sponsors
University College Dublin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18 years of age * Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol * Established diagnosis of UC and moderate-to-severe disease activity, defined as a Mayo score of 6-12, with an endoscopic subscore ≥2. * Patients had an inadequate response to, or had failed to tolerate, 1 or more of the following conventional therapies: oral 5-aminosalicylates, oral corticosteroids, azathioprine (AZA), and/or 6-mercaptopurine (6MP); or corticosteroid dependent (ie, an inability to taper corticosteroids without recurrence of UC symptoms). * Patients concurrently treated with oral 5-aminosalicylates or corticosteroids were to receive a stable dose for at least 2 weeks before baseline, and patients receiving AZA and/or 6MP were to receive a stable dose for at least 4 weeks before baseline. Patients were required to maintain stable doses of their concomitant UC medications during the study. * Female subjects of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 6 months thereafter OR * Surgical sterilized female patients with documentation of prior hysterectomy, tubal ligation or complete bilateral oophorectomy OR * Postmenopausal women with postmenopausal defined as permanent cessation \>1 year of previously occurring menses. * Female subjects' serum pregnancy test performed at the screening visit and urine pregnancy test performed at the baseline visit must be negative. * Subjects have following investigations within 1 month prior to enrolment. * Routine bloods including U&E, FBC, LFTs, inflammatory markers (CRP) and albumin will be measured. * Medical history, concomitant medications * Intradermal reaction to Tuberculin (PPD skin test) or Mycobacterium tuberculosis antigenspecific interferon-gamma release assay (IGRA) * TB screening: chest X-Ray unless performed in the last 6 months * Stool examination for enteric pathogens including Clostridium difficile * Inclusion/
Exclusion criteria
* Informed consent * Mayo score (including sigmoidoscopy unless performed in previous 3 months) * Patient's weight and height and abdominal circumference
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient Continuous Clinical Response (pCCR) | Wk 14 through to Wk 46 | Absence of clinical flare, defined as an increase in modified partial Mayo score of 2 points value with accompanying requirement for treatment intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial Mayo Score | Week 14 | Partial Mayo score consists of three subscores including stool frequency, rectal bleeding and PGA, a total score ranges from 0 - 9. |
| Modified Partial Mayo Score | Week 1 to Week 46 | A modified partial Mayo score comprises of the two PRO sub-scores, rectal bleeding and stool frequency |
| Week 14 Clinical Response | Week 14 | A decrease from BL in partial Mayo score by ≥30% or a decrease of 3 points. or A decrease from BL in modified partial Mayo of 2 points or a decrease of ≥30% from baseline. |
| Total Mayo Score | Week 1, Week 46 | The Total Mayo Score is a combined endoscopic and clinical scale used to assess the severity of UC. It is a composite of sub-scores from four categories, including stool frequency, rectal bleeding, findings at endoscopy and physician global assessment (PGA), with a total score ranging from 0 - 12. |
| Clinical Flare | Week 14 to Week 46 | UC symptom recurrence as a defined by modified partial Mayo score increase of 2 points from week 14 value with accompanying requirement for treatment intervention |
| Corticosteroid Free Remission | Week 46 | Clinical remission at WK 46 with no concomitant steroids |
| Mucosal healing | Week 46 | A Mayo endoscopic subscore of 0 or 1 |
| Clinical Remission | Week 46 | Clinical remission is defined as a Mayo score ≤2 points, with no individual sub-score \>1. |
Countries
Ireland
Contacts
Primary ContactPeter Doran, PhD
Backup ContactRabia Hussain
Outcome results
None listed