Golimumab dose variation to achieve response in Colitis

• Register: EUCTR
• Last refreshed on: 7 December 2020
• Main ID: EUCTR2015-004724-62-IE
• Date of registration: 05/11/2015
• Prospective Registration: Yes
• Primary sponsor: UCD
• Public title: Golimumab dose variation to achieve response in Colitis
• Scientific title: Golimumab (GLM) dose Optimisation to Adequate Levels to Achieve Response in Colitis. (GOAL-ARC)
• Date of first enrolment: 22/12/2015
• Target sample size: 136
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004724-62
• 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

Ireland

Contacts

• Name: Regulatory
• Affiliation: UCD

• Name: Regulatory
• Affiliation: UCD

Key inclusion & exclusion 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)
Or
? Patients that are secondary non-responders to anti-TNF agents (lost response after induction therapy) or failed to tolerate a prior anti-TNF agent
? 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.
? 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 or urine pregnancy test performed at the screening visit must be negative.
? Subjects have following investigations within 1 month prior to enrolment (during screening):
- Routine bloods including U&E, FBC, LFTs, inflammatory markers (CRP) and albumin will be measured.
- Medical history, concomitant medications
- Negative TB screening per local standard of care (unless performed and documented negative in the 6 months prior to enrolment)
- Stool examination for enteric pathogens including Clostridium difficile
- Inclusion/exclusion criteria
- Informed consent
- Mayo score (including sigmoidoscopy unless performed in previous12 weeks, +/- 4 weeks)

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 123
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

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.
? Patients who are considered primary non-responders to anti-TNF agents
? 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 equal to or greater than 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.



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

Health Condition(s) or Problem(s) studied

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

Ulcerative Colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Intervention(s)

Trade Name: Simponi
Product Name: Simponi
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: GOLIMUMAB
CAS Number: 476181-74-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: GOLIMUMAB
CAS Number: 476181-74-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): 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, from WK 14 through to WK 46

Secondary Objective: To determine if the intensive monitoring if:
• FCP and drug levels of GLM (when commenced immediately post induction) to guide dose intensification improves rates of clinical response to induction measured at week 14 vs. standard treatment doses.
• FCP and drug levels of GLM (when commenced immediately post induction) to guide dose intensification results in lower levels of measured FCP at week 46.
• GLM drug levels and FCP and concentration based dosing leads to higher rates of corticosteroid free remission at WK 46
• GLM drug levels and FCP and concentration based dosing has an impact of patient reported outcomes of QOL
• Drug levels and FCP with guided dose intensification or dose de-escalation results in higher rates of mucosal healing
• Drug levels and FCP with guided dose intensification or dose de-escalation results in differences in histological markers of inflammation using the Goebes scoring system and presence of basal plasmacytosis.

Timepoint(s) of evaluation of this end point: from week 14 to week 46

Main Objective: To ascertain if use of intensive monitoring of FCP and drug levels of GLM (during maintenance) to guide dose intensification improves rates of pCCR and reduces disease activity in UC.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Measured across 46 week participation in trial and dependent on treatment arm.

Secondary end point(s): 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.

Partial Mayo score
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
A modified partial Mayo score comprises of the two PRO sub-scores, rectal bleeding and stool frequency.

Clinical Remission
Clinical remission is defined as a Mayo score =2 points, with no individual sub-score >1.

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

Corticosteroid Free Remission
Clinical remission at WK 46 with no concomitant steroids

Mucosal Healing
A Mayo endoscopic subscore of 0 or 1

Histological Remission
Histological remission is defined as grade 0 in the Geboes Index

Secondary ID(s)

UCDCRC/15/007

Source(s) of Monetary Support

MSD

Ethics review

Status: Approved
Approval date: 22/12/2015
Contact: