Golimumab (GLM) Dose Optimisation to Adequate Levels to Achieve Response in Colitis

Colitis Clinical Trial

— GOAL-ARC  

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).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02687724
• Other study ID #: UCDCRC/15/007
• Status: Recruiting
• Phase: Phase 4
• Start date: June 2016
• Est. completion date: February 2020

Study information

• Verified date: July 2018
• Source: University College Dublin
• Contact: Peter Doran, PhD
• Email: peter.doran[@]ucd.ie
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 136
• Est. completion date: February 2020
• Est. primary completion date: February 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colitis

Intervention

Drug:
• Golimumab (GLM)
GLM is a human IgG1? monoclonal antibody produced by a murine hybridoma cell line with recombinant DNA technology

Locations

Country	Name	City	State
Ireland	St Vincent's University Hospital	Dublin

Sponsors (1)

Lead Sponsor	Collaborator
University College Dublin

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient Continuous Clinical Response (pCCR)	Absence of clinical flare, defined as an increase in modified partial Mayo score of 2 points value with accompanying requirement for treatment intervention	Wk 14 through to Wk 46
Secondary	Total Mayo Score	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.	Week 1, Week 46
Secondary	Partial Mayo Score	Partial Mayo score consists of three subscores including stool frequency, rectal bleeding and PGA, a total score ranges from 0 - 9.	Week 14
Secondary	Modified Partial Mayo Score	A modified partial Mayo score comprises of the two PRO sub-scores, rectal bleeding and stool frequency	Week 1 to Week 46
Secondary	Week 14 Clinical Response	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.	Week 14
Secondary	Clinical Remission	Clinical remission is defined as a Mayo score =2 points, with no individual sub-score >1.	Week 46
Secondary	Clinical Flare	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	Week 14 to Week 46
Secondary	Corticosteroid Free Remission	Clinical remission at WK 46 with no concomitant steroids	Week 46
Secondary	Mucosal healing	A Mayo endoscopic subscore of 0 or 1	Week 46