A Clinical Trial of Antibody GSK1070806 in the Treatment of Patients With Moderate to Severe Crohn's Disease

NCT03681067 | Completed Phase 1 DMC

• 2 other identifiers: RG_17-2582018-002001-65
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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).

Conditions

Crohn Disease

Keywords

Crohn's disease; CDAID; CDAI; GSK1070806

Outcome Measures

Primary Outcomes (9)

• Safety and tolerability parameters include: adverse events and serious adverse events

  NCI-CTCAE criterion Version 4

  24 weeks

• Safety and tolerability parameters include: clinical laboratory tests (Haematology)

  Haematology panel : haemoglobin (g/L), Platelets (10\*9/L), White Blood Cells (10\*9/L), International normalized ratio, Neutrophils (10\*9/L)

  24 weeks

• Safety and tolerability parameters include: clinical laboratory tests (Biochemistry)

  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)

  24 weeks

• Safety and tolerability parameters include: Cardiology

  Electrocardiogram review - for any abnormalities i.e. QT interval etc.

  24 weeks

• Safety and tolerability parameters include: frequency, type and severity of infections

  NCI-CTCAE criterion Version 4 - grading system used

  24 weeks

• Safety and tolerability parameters include: Heart Rate (vital signs)

  Heart rate

  24 weeks

• Safety and tolerability parameters include: Blood Pressure (vital signs)

  Blood pressure

  24 weeks

• Safety and tolerability parameters include: Body Temperature (vital signs)

  Oral body temperature

  24 weeks

• Safety and tolerability parameters include: Respiratory Rate (vital signs)

  Respiratory rate

  24 weeks

Secondary Outcomes (1)

• CDAI score over time. Patients

  28 weeks

Study Arms (2)

GSK10708060

EXPERIMENTAL

Humanised antibody GSK1070806

Drug: GSK1070806

Placebo - sodium chloride

PLACEBO COMPARATOR

Placebo

Drug: Placebo- sodium chloride

Interventions

GSK1070806 DRUG

GSK1070806 100mg/ml injectable solution will be delivered via intravenous infusion as a single infusion

GSK10708060

Placebo- sodium chloride DRUG

Placebo injectable solution will be delivered via intravenous infusion as a single infusion

Also known as: Placebo

Placebo - sodium chloride

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.\*
• A patient is eligible to participate if she is not pregnant.
• A woman of childbearing potential (WOCBP) is eligible only if she meets at least one of the following conditions:
• i. Females on HRT and whose menopausal status is in doubt will be required to use one of the non-hormonal highly effective contraception methods if they wish to continue their HRT during the trial. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before trial enrolment.
• ii. Agrees to follow the contraceptive guidance in Appendix 5 for at least 180 days post-dose of trial medication. If a hormonal method of birth control is selected from the list in Appendix 5 then patients must have been using these methods at least 1 month prior to GSK1070806 administration, or be abstinent, or utilise a condom as a method of contraception until the selected hormonal method has been in place for the 28 day period.
• A woman who is not of childbearing potential is eligible only if she meets at least one of the following conditions:
• i. Premenopausal female with documented hysterectomy ii Premenopausal female with documented bilateral salpingectomy or oophorectomy iii. Postmenopausal female defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement

You may not qualify if:

• 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
• Viral and bacterial infections:
• Presence of Hepatitis B surface antigen (HBsAg), (confirmed by Hepatitis B surface antigen test - within 12 months of randomisation) core antigen (HBcAg) or surface antibody (HBsAb), positive Hepatitis C (qualitative enzyme immunoassay) test result
• Known varicella, herpes zoster, or other severe viral infection within 6 weeks of randomisation
• The participant has a history of tuberculosis (TB) disease or latent TB infection, in the absence of documented adequate therapy for same.
• Positive screening test for TB (including T-SPOT.TB TB test), unless respiratory review confirms false positive test results
• History of uncontrolled bacterial or fungal infection requiring intravenous antibiotics

Sponsors & Collaborators

• University of Birmingham: lead
• GlaxoSmithKline: collaborator
• University Hospital Birmingham: collaborator

Study Sites (1)

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

GSK1070806

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Marietta Iacucci, MD,PhD

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: September 21, 2018
• Study Start: February 20, 2019
• Primary Completion: June 2, 2020
• Study Completion: June 2, 2020
• Last Updated: April 28, 2021

Record last verified: 2021-04

Locations

GB (1)