Ulcerative Colitis MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856
Conditions
Interventions
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)
Conce
Sponsors
UCD
Eligibility
Sex/Gender
All
Inclusion 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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 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. ;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 ;Timepoint(s) of evaluation of this end point: from week 14 to week 46 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 ;Timepoint(s) of evaluation of this end point: Measured across 46 week participation in trial and dependent on treatment arm. | — |
Countries
Ireland
Contacts
Public ContactRegulatory
UCD
Outcome results
None listed