Clinical Trials Register

Summary
EudraCT Number:	2015-003089-96
Sponsor's Protocol Code Number:	204851
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-10-13
Trial results	View 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

2015-003089-96

A.3

Full title of the trial

A multi-centre Phase IIa double-blind, placebo-controlled study to investigate the efficacy and safety of GSK3196165 in subjects with inflammatory hand osteoarthritis.

A.3.1

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

A clinical study to investigate the effectivness and safety of GSK3196165 in patients with inflammatory hand osteoarthritis

A.4.1

Sponsor's protocol code number

204851

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02683785

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	GlaxoSmithKline Research & Development Ltd
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline Research & Development Ltd
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	GlaxoSmithKline Research & Development Ltd
B.5.2	Functional name of contact point	Clinical Trials HelpDesk
B.5.3	Address:
B.5.3.1	Street Address	Iron Bridge road
B.5.3.2	Town/ city	Uxbridge
B.5.3.3	Post code	UB11 1BT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44208990 4466
B.5.5	Fax number	+44208990 1234
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

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.3.2	Product code	GSK3196165
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/A
D.3.9.1	CAS number	1638332-55-4
D.3.9.2	Current sponsor code	GSK3196165
D.3.9.3	Other descriptive name	Anti human granulocyte-macrophage colony-stimulating factor (GM-CSF) monoclonal
D.3.9.4	EV Substance Code	SUB177902
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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	Yes
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
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Inflammatory Hand Osteoarthritis

E.1.1.1

Medical condition in easily understood language

A clinical study to investigate the effectiveness and safety of GSK3196165 in patients with inflammatory hand osteoarthritis

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10019115
E.1.2	Term	Hand osteoarthritis
E.1.2	System Organ Class	100000004859

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy potential of GSK3196165 on pain in inflammatory
HOA.

E.2.2

Secondary objectives of the trial

- To evaluate impact of GSK3196165 on average and worst HOA pain, over time.
- To assess the impact of GSK3196165 on hand pain (on use), stiffness and function, over time.
- To assess the impact of GSK3196165 on HOA inflammation.
-To assess potential impact of GSK3196165 on disease activity in HOA.
- To assess safety of GSK3196165 in HOA patients, over the study duration.
-To assess population pharmacokinetics of GSK3196165 in HOA.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

AGE
1. Age ≥ 18 years at the time of signing the informed consent.
TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY
2. Meets ACR classification of OA and is intolerant to, or has not responded to analgesics (level 1 and 2) or to NSAIDs for at least 10 days in the past 3 months.
3. Must have active disease with at least two swollen and tender PIP and/or DIP joints in the affected hand*.
4. Signs of inflammation such as synovitis in the MRI scan of the affected hand*.
5. Must have a patient’s self assessment of 24h average hand pain intensity of at least ‘5’ on an 11-point NRS (0-10), calculated as an average using data from the 7 days prior to assessment date.
*If only one hand is affected by HOA and meets the inclusion criteria, the affected hand will be documented at screening and used for all assessments. In cases where both hands are affected by HOA and both meet the inclusion criteria, then the dominant hand will be documented at screening and this hand will be used for the MRI assessments throughout the study.

WEIGHT
6. Body weight ≥ 45 kg.

SEX
7. Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria detailed in Appendix 5.

INFORMED CONSENT
8. Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications.

OTHER SAFETY-RELATED
9. Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 70 % predicted and forced expiratory volume in 1 second (FEV1) ≥ 80 % predicted.
10. No evidence of active or latent infection with Mycobacterium tuberculosis (TB), as defined by all of the following:
a. No history of active or latent TB infection irrespective of treatment status.
b. A negative diagnostic TB test within 28 days of baseline (Day 1) defined as: a negative QuantiFERON Gold test or T-spot test (may be performed locally) (NB: 2 successive indeterminate QuantiFERON tests will be considered as a positive result).
Note: If there has been recent close contact with persons who have active TB prior to study enrolment the subject will be referred to a TB physician to undergo additional evaluation.

E.4

Principal exclusion criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER FUNCTION AND QTc INTERVAL)
1. Pregnant or lactating females.
2. Significant unstable or uncontrolled acute or chronic disease please view protocol for further information.
3. History of any clinically significant inflammatory disease other than inflammatory HOA, especially, but not limited to, rheumatoid arthritis or spondylarthropathies.
4. Diagnosis of rheumatoid arthritis, fibromyalgia, gout, calcium pyrophosphate deposition disease CPPD, pseudogout,hemochromatosis or other inflammatory rheumatological or autoimmune disorders.
5. Clinical suspicion of, or previous investigation for CPPD or pseudogout, or history of chondrocalcinosis.
6. Any injury, medical or surgical procedure to the affected joint(s) that may interfere with evaluation of the target HOA joint(s).
7. History of any clinically-significant respiratory disease that required treatment and/or follow up under the direction of a physician or any respiratory disease. Please view protocol for further information.
8. Clinically-significant or unstable (in the opinion of the Investigator) persistent cough or dyspnea that is unexplained.
9. QTc > 450 msec or QTc > 480 msec in subjects with Bundle Branch Block based on averaged values of triplicate electrocardiograms obtained over a brief (e.g. 5-10 minute) recording period
-The QTc is the QT interval corrected for heart rate according to Bazett’s formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machine read or manually over-read.
10. ALT >2xULN and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
11. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
12. A history of malignant neoplasm within the last 10 years or breast cancer within the last 20 years, except for non-melanoma skin cancers that have been excised and cured or carcinoma in situ of the uterine cervix.
13. Kidney disease: Current or history of renal disease, or estimated creatinine clearance <60 mL/min/1.73m2 or serum creatinine >1.5xULN within 28 days of Day 1.
14. Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
15. History of infected joint prosthesis at any time, with the prosthesis still in situ. History of leg ulcers, catheters, chronic sinusitis or recurrent chest or urinary tract infections.
16. Active infections, or history of recurrent infections (excluding recurrent fungal infections of the nail bed), or have required management of acute or chronic infections, please view protocol for further information.
17. A vaccination (live or attenuated) within 30 days of Day 1 or BCG vaccination within 365 days of Day 1, or a live vaccination planned during the course of the study.
18. Any surgical procedure, including bone or joint surgery/synovectomy within 12 weeks prior to Day 1 or any planned surgery within the duration of the study or follow-up period.
19. Contraindication to MRI scanning (as assessed by local MRI safety questionnaire) which includes but not limited to:
a. Intracranial aneurysm clips (except Sugita) or other metallic objects,
b. History of intra-orbital metal fragments that have not been removed by an medical professional,
c. Pacemakers or other implanted cardiac rhythm management devices and non- MR compatible heart valves,
d. Inner ear implants, except MR-conditional implants scanned within manufacturer guidelines,
e. History of claustrophobia which may impact participation
20. Use any of prohibited medications, as listed in section 6.10.2 of the protocol, throughout the study until after completion of the week 22 follow-up visit.
21. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within a year prior to Day 1.
22. History of sensitivity to any of the study treatments, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
23. Contraindication to gadolinium contrast agent as assessed by the site.
24. Must have negative titer rheumatoid factor (RF) and anti-CCP antibody.
-Please view protocol for further information from (points 25 to 32)

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in 24h average hand pain intensity.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 6.

E.5.2

Secondary end point(s)

Change from baseline in 24h average hand pain intensity at each visit, measured by daily pain NRS and averaged over the 7 days prior to each assessment visit.
• Change from baseline of worst hand pain intensity over 24h at each visit, measured by daily NRS and averaged over the 7 days prior to each assessment visit.
• Proportion of subjects in each treatment group achieving a 30% reduction in 24h average hand pain intensity at each visit, measured by daily NRS averaged over the 7 days prior to assessment visit.
• Proportion of subjects in each treatment group achieving a 50% reduction in 24h average hand pain intensity at each visit, measured by daily NRS averaged over the 7 days prior to assessment visit.
• Proportion of subjects in each treatment group achieving a 30% reduction in 24h worst hand pain intensity at each visit, measured by daily NRS averaged over the 7 days prior to assessment visit.
• Proportion of subjects in each treatment group achieving a 50% reduction in 24h worst hand pain intensity at each visit, measured by daily NRS averaged over the 7 days prior to assessment visit.
• Change from baseline in Australian Canadian Hand Osteoarthritis Index (AUSCAN) 3.1 NRS, total and domains (pain, morning stiffness, function) scores at each visit.
• Change in number of swollen and tender hand joints at each visit.
• Change from baseline in patient global assessment (PtGA) and physician global assessment (PhGA) of disease activity at Week 6 and 12 and week 22.
• Incidence of adverse events and serious adverse events.
• Incidence of infections.
• Incidence of pulmonary events (cough/dyspnea, PAP and DLCO).
• Immunogenicity.
• Population pharmacokinetics endpoints such as CL/F, Vss/F, Ka

E.5.2.1

Timepoint(s) of evaluation of this end point

Pain (Week 6, 12, 22), hand function (Week 0, 1, 2, 4, 6, 8, 10, 12) safety (throughout the study), pharmacokinetics (Day 0, 3, 8, 29 and 43,85,155), inflammation (Week 0, 1, 2, 4, 6, 8, 10, 12, 22) and disease activity (Week 0, 2)

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

Yes

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)

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)

Yes

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

Yes

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

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

LSLV

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

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Subjects will not receive any additional treatment from GSK after completion of the study because the efficacy of GSK3196165 has not yet been defined. Treatment after the end of the study will continue as per the standard of care for HOA at the site. The investigator is responsible for ensuring that consideration has been given to the poststudy care of the subject’s medical condition, whether or not GSK is providing specific post-study treatment.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-01-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-11-29

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IMP with orphan designation in the indication
Orphan Designation Number:
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