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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03681067
Recruitment Status : Recruiting
First Posted : September 21, 2018
Last Update Posted : April 3, 2019
Sponsor:
Collaborators:
GlaxoSmithKline
University Hospital Birmingham
Information provided by (Responsible Party):
University of Birmingham

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).

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: GSK1070806 Drug: Placebo- sodium chloride Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 20, 2019
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: GSK10708060
Humanised antibody GSK1070806
Drug: GSK1070806
GSK1070806 100mg/ml injectable solution will be delivered via intravenous infusion as a single infusion

Placebo Comparator: Placebo - sodium chloride
Placebo
Drug: Placebo- sodium chloride
Placebo injectable solution will be delivered via intravenous infusion as a single infusion
Other Name: Placebo




Primary Outcome Measures :
  1. Safety and tolerability parameters include: adverse events and serious adverse events [ Time Frame: 24 weeks ]
    NCI-CTCAE criterion Version 4

  2. 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)

  3. 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)

  4. Safety and tolerability parameters include: Cardiology [ Time Frame: 24 weeks ]
    Electrocardiogram review - for any abnormalities i.e. QT interval etc.

  5. Safety and tolerability parameters include: frequency, type and severity of infections [ Time Frame: 24 weeks ]
    NCI-CTCAE criterion Version 4 - grading system used

  6. Safety and tolerability parameters include: Heart Rate (vital signs) [ Time Frame: 24 weeks ]
    Heart rate

  7. Safety and tolerability parameters include: Blood Pressure (vital signs) [ Time Frame: 24 weeks ]
    Blood pressure

  8. Safety and tolerability parameters include: Body Temperature (vital signs) [ Time Frame: 24 weeks ]
    Oral body temperature

  9. Safety and tolerability parameters include: Respiratory Rate (vital signs) [ Time Frame: 24 weeks ]
    Respiratory rate


Secondary Outcome Measures :
  1. CDAI score over time. Patients [ Time Frame: 28 weeks ]
    Crohns disease activity index score (Pre-treatment, Post treatment). Scale ranges from <150(remission) to >450(severe Crohn's disease).



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

A patient will be eligible for inclusion in this study only if all of the following criteria apply:

  1. Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications. (see Section 7.11 for additional information)
  2. Patients that have been diagnosed with moderate to severe Crohn's disease for at least 3 months prior to Screening Visit 1 defined by CDAI score between 220-450
  3. Patients are required to have endoscopic evidence of active Crohn's disease at Baseline (screening visit 1) defined by endoscopic appearance: SES-CD excluding the narrowed component of ≥ 6 (or ≥4 for patients with isolated ileal disease).
  4. AST and ALT ≤ 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
  5. Male or female participants aged ≥16 years (up to 80 years)

    Male participants:

  6. 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:

7. A female participant is eligible to participate if she is not pregnant or breastfeeding and not a woman of childbearing potential (WOCBP) defined as 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 therapy (HRT). However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

iv. 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.

v. A WOCBP who 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 1 then participants must have been using these methods at least 28 days 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.

Exclusion Criteria:

A participant will not be eligible for inclusion in this trial if any of the following criteria apply:

  1. Diagnosis of ulcerative or indeterminate colitis

    Crohn's Disease complications:

  2. Evidence of an infected abscess by MRI or other examinations
  3. 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
  4. Participants with ileostomies, colostomies or rectal pouches
  5. Participants with a bowel stricture that is fixed
  6. Participants with evidence of short bowel syndrome
  7. Participants requiring enteral or parenteral feeding
  8. Deep penetrating ulcers at endoscopy thought to be at risk for perforation

    Viral and bacterial infections:

  9. 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
  10. Known varicella, herpes zoster, or other severe viral infection within 6 weeks of randomisation
  11. The participant has a history of tuberculosis (TB) disease or latent TB infection, in the absence of documented adequate therapy for same.
  12. Positive screening test for TB (including T-SPOT.TB TB test), unless respiratory review confirms false positive test results
  13. History of uncontrolled bacterial or fungal infection requiring intravenous antibiotics
  14. Positive immunoassay for Clostridium difficile toxin and other enteric pathogens

    Other exclusion criteria:

  15. Cardiology assessment/co-morbidity defined as:

    i. QTc >450 msec (480msec for those with Bundle Branch Block) and/or ii. either QTcb or QTcf, machine or manual overread, males or females. The QT correction formula used to determine exclusion and discontinuation should be the same throughout the trial and/or iii. based on single QTc value (average of triplicate readings) of ECG obtained over a brief recording period

  16. The participant has congenital or acquired immunodeficiency, or a history of chronic or recurrent opportunistic infections
  17. The participant has current evidence of, or has been treated for a malignancy within the past five years (other than localised basal cell, squamous cell skin cancer, cervical dysplasia, or cancer in situ that has been resected)
  18. Use of any investigational drug within 30 days prior to screening, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
  19. Participant has received live, attenuated or recombinant vaccine(s) within 2 months of randomisation or will require vaccination within 3 months of trial drug infusion
  20. Any patients that are receiving medication(s) detailed in Section 7.11.2 of the trial protocol, will not be eligible for randomisation into the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03681067


Contacts
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Contact: Marietta Iacucci, MD, PhD +44(0)121 3718119 m.iacucci@bham.ac.uk
Contact: Manpreet K Wilkhu, BSc +44(0)121 3718165 m.k.wilkhu@bham.ac.uk

Locations
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United Kingdom
University Hospitals Birmingham NHS Foundation Trust Recruiting
Birmingham, United Kingdom, B15 2TH
Contact: Marietta Iacucci    +44 (0)121 3718119    m.iacucci@bham.ac.uk   
Contact: Manpreet K Wilkhu    +44(0)121 3718165    CDAID@trials.bham.ac.uk   
Sponsors and Collaborators
University of Birmingham
GlaxoSmithKline
University Hospital Birmingham
Investigators
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Principal Investigator: Marietta Iacucci, MD,PhD University of Birmingham

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Responsible Party: University of Birmingham
ClinicalTrials.gov Identifier: NCT03681067    
Other Study ID Numbers: RG_17-258
2018-002001-65 ( EudraCT Number )
First Posted: September 21, 2018    Key Record Dates
Last Update Posted: April 3, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Birmingham:
Crohn's disease
CDAID
CDAI
GSK1070806
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs