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

NCT02687724 | Unknown Phase 4 DMC

• 1 other identifier: UCDCRC/15/007
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

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.

Conditions

Colitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Total Mayo Score

  Week 1, Week 46

• Partial Mayo Score

  Week 14

• Modified Partial Mayo Score

  Week 1 to Week 46

• Week 14 Clinical Response

  Week 14

• Clinical Remission

  Week 46

Study Arms (2)

Standard treatment as per SmPC

ACTIVE COMPARATOR

Patients will receive standard loading dose of GLM of 200/100 mgs at WKS 0 \& 2. They will then receive 100mgs/ 50mgs depending on their weight as per SmPC. Patients will report their modified partial mayo score and SHS score every 4 weeks (PRO) and provide it to the investigator site via a web based application.

Drug: Golimumab (GLM)

Intervention Arm

EXPERIMENTAL

Patients will receive standard loading dose of GLM of 200/100 mgs at WKS 0 \& 2. As with Group 1, Patients will report their modified partial mayo and SHS score every four weeks ( the window for this will be +/- one week) and provide it to the investigator site via a web based application. In addition FCP, GLM DL and ADA shall be measured every four weeks.

Drug: Golimumab (GLM)

Interventions

Golimumab (GLM) DRUG

GLM is a human IgG1κ monoclonal antibody produced by a murine hybridoma cell line with recombinant DNA technology

Intervention Arm; Standard treatment as per SmPC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Informed consent
• Mayo score (including sigmoidoscopy unless performed in previous 3 months)
• Patient's weight and height and abdominal circumference
• 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

Sponsors & Collaborators

• University College Dublin: lead

Study Sites (1)

St Vincent's University Hospital

Dublin, Ireland

RECRUITING

MeSH Terms

Conditions

Colitis

Interventions

golimumab

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Glen Doherty

  g.doherty@st-vincents.ie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Doran, PhD

CONTACT

peter.doran@ucd.ie

Rabia Hussain

CONTACT

rabia.hussain@ucd.ie

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2016
• First Posted: February 22, 2016
• Study Start: June 1, 2016
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: July 19, 2018

Record last verified: 2018-07

Locations

IE (1)