Clinical trial NCT02687724: Golimumab (GLM) Dose Optimisation to Adequate Levels to Achieve Response in Colitis
Official title: 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).
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Colitis
Lead sponsor: University College Dublin
Sponsor class: OTHER
First posted: 2016-02-22
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Exclusion Criteria:

* Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study
* Patients aged \<18 years of age
* Patients who cannot give informed consent,
* Pregnant patients or those who are breastfeeding will be deemed ineligible.
* Prior treatment with any anti-TNF agent
* Contra-indication to use of GLM (Hypersensitivity to the active substance or to any of the excipients; Active tuberculosis (TB), acute or chronic Hepatitis B infection or other severe infections such as sepsis and/or opportunistic infections including HIV infection; Moderate or severe heart failure (NYHA class III/IV)
* Have symptoms or signs suggestive of current active or latent TB upon medical history, physical examination and/or chest radiograph, or positive Mycobacterium tuberculosis antigen-specific interferon-gamma release assay (IGRA)
* Patients with a history of, or at imminent risk for, colectomy; who required gastrointestinal surgery within 2 months before screening;
* History of colonic mucosal dysplasia or adenomatous colonic polyps that were not removed
* Screening stool study positive for enteric pathogens or Clostridium difficile toxin.
* Oral corticosteroids at a dose \>40 mg prednisone or its equivalent per day; receipt of cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 8 weeks before the first study agent injection; or use of an investigational agent within 5 half-lives of that agent before the first study agent injection.
* Patients in recent receipt of live vaccinations within 4 weeks prior to enrolment

Primary outcomes:
measure: Patient Continuous Clinical Response (pCCR)
timeFrame: Wk 14 through to Wk 46
Secondary outcomes:
measure: Total Mayo Score
timeFrame: Week 1, Week 46
measure: Partial Mayo Score
timeFrame: Week 14
measure: Modified Partial Mayo Score
timeFrame: Week 1 to Week 46
measure: Week 14 Clinical Response
timeFrame: Week 14
measure: Clinical Remission
timeFrame: Week 46
measure: Clinical Flare
timeFrame: Week 14 to Week 46
measure: Corticosteroid Free Remission
timeFrame: Week 46
measure: Mucosal healing
timeFrame: Week 46
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: St Vincent's University Hospital
Study officials:
affiliation: g.doherty@st-vincents.ie
name: Glen Doherty
role: PRINCIPAL_INVESTIGATOR
References: