A Phase Ib/IIb, Randomised, Double Blind, Placebo-Controlled Trial to Investigate the Safety, Tolerability and Clinical Activity of Humanised Antibody GSK1070806 in the Treatment of Patients With Moderate-to-Severe Crohn's Disease
Overview
- Phase
- Phase 1
- Intervention
- GSK1070806
- Conditions
- Crohn Disease
- Sponsor
- University of Birmingham
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Safety and tolerability parameters include: adverse events and serious adverse events
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This trial aims to investigate the safety, tolerability and clinical activity of humanised antibody GSK1070806 delivered via intravenous infusion in the treatment of patients with moderate-to-severe Crohn's disease. 30-36 patients will be enrolled into the trial, with two thirds of the patients receiving active drug and one third receiving placebo. After 30 patients have been recruited into the study the sample size will be reassessed and up to an additional 6 patients could be recruited (i.e. up to 36 patients).
Detailed Description
The proposed study will be a randomised, double blind, placebo-controlled trial to investigate the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of single intravenous infusion (one dose on Day 1) of GSK1070806 or placebo, in patients with active, moderate to severe CD. The primary objective of the study is to assess the safety and tolerability of a single dose IV administration of GSK1070806. A secondary objective will be to evaluate the effect of GSK1070806 in change of CDAI over time. Further secondary endpoints will include assessment of endoscopic response in patients at week 12. (Other secondary endpoints are detailed in Section 2.3). 30 patients will be recruited with randomisation of 2:1 active drug to placebo in multiple centres in the UK. After 30 patients have been recruited into the study the sample size will be reassessed and up to an additional 6 patients could be recruited (i.e. up to 36 patients). These additional patients will also be recruited with randomisation of 2:1 active drug to placebo. An initial screening shall take place to identify patients diagnosed with CD for at least 3 months prior to screening, active disease based on CDAI score of 220-450 points and colonoscopic confirmation of active mucosal inflammation (SES-CD excluding narrowed component ≥6; or in patients with isolated ileal disease ≥4). Patients who do not have colonoscopically demonstrated mucosal inflammation will be excluded even if they have MRI evidence of Crohn's disease more proximally in the small intestine. For inclusion, CDAI criteria have to be fulfilled within 7 days prior to dosing and colonoscopic SES-CD criteria has to be fulfilled with 28 days prior to dosing. The induction of clinical activity will be assessed at week 12 by CDAI score, average clinical SF and/or AP scores as well as by colonoscopic assessment of baseline video images and week 12 video images. The first 5 patients randomised into the trial will be dosed at least 3 days apart. At the interim analysis time point, a safety decision will be taken on the subsequent recruitment and patient spacing out strategy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A patient will be eligible for inclusion in this study only if all of the following criteria apply:
- •Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications. (see Section 7.11 for additional information)
- •Patients that have been diagnosed with moderate to severe Crohn's disease for at least 3 months prior to Screening Visit 1
- •Patients are required to have endoscopic evidence of active Crohn's disease at Baseline defined by endoscopic appearance: SES-CD excluding the narrowed component of ≥ 6 (or ≥4 for patients with isolated ileal disease).
- •AST and ALT ≤ 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)
- •Male or female participants aged ≥16 years (up to 80 years)
- •Male participants:
- •A male participant must agree to use contraception as detailed in Appendix 5 of this protocol for at least 180 days post-dose of study medication and refrain from donating sperm during this period.
- •Female participants:
- •If the patient is breastfeeding, she must agree to stop breastfeeding once randomised into the trial.\*
Exclusion Criteria
- •A participant will not be eligible for inclusion in this trial if any of the following criteria apply:
- •Diagnosis of ulcerative or indeterminate colitis
- •Crohn's Disease complications:
- •Evidence of an infected abscess by MRI or other examinations
- •Bowel surgery other than appendectomy within 12 weeks prior to screen and/or has planned surgery or deemed likely to need surgery for CD during the trial period
- •Participants with ileostomies, colostomies or rectal pouches
- •Participants with a bowel stricture that is fixed
- •Participants with evidence of short bowel syndrome
- •Participants requiring enteral or parenteral feeding
- •Deep penetrating ulcers at endoscopy thought to be at risk for perforation
Arms & Interventions
GSK10708060
Humanised antibody GSK1070806
Intervention: GSK1070806
Placebo - sodium chloride
Placebo
Intervention: Placebo- sodium chloride
Outcomes
Primary Outcomes
Safety and tolerability parameters include: adverse events and serious adverse events
Time Frame: 24 weeks
NCI-CTCAE criterion Version 4
Safety and tolerability parameters include: clinical laboratory tests (Haematology)
Time Frame: 24 weeks
Haematology panel : haemoglobin (g/L), Platelets (10\*9/L), White Blood Cells (10\*9/L), International normalized ratio, Neutrophils (10\*9/L)
Safety and tolerability parameters include: clinical laboratory tests (Biochemistry)
Time Frame: 24 weeks
Biochemistry Panel : Creatinine (umol/L), Sodium (mmol/L), Potassium (mmol/l), Bilirubin (umol/L), Alanine Transferase (u/L) Aspartate Transaminase (U/L), Albumin (g/L), eGFR ml/min/1.7, C-Reactive Protein (CRP)
Safety and tolerability parameters include: Blood Pressure (vital signs)
Time Frame: 24 weeks
Blood pressure
Safety and tolerability parameters include: Heart Rate (vital signs)
Time Frame: 24 weeks
Heart rate
Safety and tolerability parameters include: Body Temperature (vital signs)
Time Frame: 24 weeks
Oral body temperature
Safety and tolerability parameters include: Respiratory Rate (vital signs)
Time Frame: 24 weeks
Respiratory rate
Safety and tolerability parameters include: Cardiology
Time Frame: 24 weeks
Electrocardiogram review - for any abnormalities i.e. QT interval etc.
Safety and tolerability parameters include: frequency, type and severity of infections
Time Frame: 24 weeks
NCI-CTCAE criterion Version 4 - grading system used
Secondary Outcomes
- CDAI score over time. Patients(28 weeks)