Clinical Trials Register

Summary
EudraCT Number:	2018-002001-65
Sponsor's Protocol Code Number:	RG_17-258
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-10-01
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2018-002001-65

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A clinical trial of antibody GSK1070806 in the treatment of patients with moderate to severe Crohn’s Disease

A.3.2

Name or abbreviated title of the trial where available

CDAID GSK1070806

A.4.1

Sponsor's protocol code number

RG_17-258

A.5.4

Other Identifiers

Name:

EudraCT

Number:

2018-002001-65

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	University of Birmingham
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline (GSK)
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University of Birmingham
B.5.2	Functional name of contact point	Dr Marietta Iacucci
B.5.3	Address:
B.5.3.1	Street Address	Office 16, 1st Floor ITM, Heritage Building, Mindelsohn Way
B.5.3.2	Town/ city	Birmingham
B.5.3.3	Post code	B15 2TH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01213718119
B.5.6	E-mail	m.iacucci@bham.ac.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	GSK1070806
D.3.4	Pharmaceutical form	Concentrate for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GSK1070806
D.3.9.2	Current sponsor code	GSK1070806
D.3.9.3	Other descriptive name	fully humanised, recombinant monoclonal antibody (IgG1)
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Crohn's disease

E.1.1.1

Medical condition in easily understood language

Crohn's disease

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10013099
E.1.2	Term	Disease Crohns
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the trial is to assess the safety, tolerability and clinical activity of an antibody GSK1070806 in patients with moderate to severe Crohn's disease.

E.2.2

Secondary objectives of the trial

The secondary objectives of the trial are:

1. To evaluate the clinical activity of single dose IV administrations of GSK1070806 in patients with moderate to severe CD.

2. To evaluate the serum pharmacokinetics (PK) following single dose IV administrations of GSK1070806 in patients with moderate to severe CD.

3. To evaluate the proportion of patients with moderate to severe Crohn’s disease achieving clinical remission following single dose IV administrations of GSK1070806.

4. Time to clinical response following single dose IV administrations of GSK1070806 in patients with moderate to severe CD.

5. To evaluate the effect of GSK1070806 on established biomarkers of disease in patients with moderate to severe Crohn’s disease.

6. To evaluate the potential of anti-GSK1070806 antibody formation following administration of GSK1070806 in patients with moderate to severe CD.

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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

E.5 End points

E.5.1

Primary end point(s)

Safety and tolerability parameters include: adverse events, serious adverse events, clinical laboratory tests, electrocardiograms and vital signs. Frequency, type and severity of infections.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 24 - Follow Up Visit 10

E.5.2

Secondary end point(s)

Key secondary outcome measure: CDAI score over time

Further Secondary Outcome Measures
1. Serum concentrations of GSK1070806 over time and derived PK parameters if feasible AUC(0-τ), Cmax, Tmax and t½.
2. Abdominal pain (AP) over time.
3. Stool frequency (SF) over time.
4. Post-treatment (w12) SES-CD endoscopic score, adjusted for baseline value.
5. Proportion of patients in clinical remission defined as average daily Stool Frequency < 2.8 and /or average daily Abdominal pain < 1 and CDAI <150.
6. Kinetics of induction of clinical response defined as a > 70 point decrease from baseline CDAI score (or score < 150).
7. Serum C-reactive protein over time.
8. Faecal calprotectin over time.
9. Incidence and titers of serum of anti-GSK1070806 antibodies before and after GSK1070806 administration.

E.5.2.1

Timepoint(s) of evaluation of this end point

All outcome measures will be evaluated at Week 24 last Follow Up Visit 10, apart from Post - treatment SES-CD which will be evaluated at Week 12.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of trial will be the date of Last Patient Last Visit (LPLV).

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1