Study to explore and compare the effects of a new drug in combination with methotrexate therapy in people with early and established rheumatoid arthritis.

• Register: EUCTR
• Last refreshed on: 7 January 2019
• Main ID: EUCTR2015-004386-91-PL
• Date of registration: 20/07/2016
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public title: Study to explore and compare the effects of a new drug in combination with methotrexate therapy in people with early and established rheumatoid arthritis.
• Scientific title: A Phase IIa, Double-Blind, Mechanistic Study of GSK3196165 in Combination with Methotrexate Therapy in Subjects with Active Rheumatoid Arthritis Despite Treatment with DMARDs
• Date of first enrolment: 26/08/2018
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004386-91
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Poland, United States

Contacts

• Name: GSK Clinical Support HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: GSK Clinical Support HelpDesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age =18 years at the time of signing informed consent.
2. Meets ACR/EULAR 2010 RA Classification Criteria
AND Subject not diagnosed before age of 16 years.
3. Functional class I, II or III defined by the 1992 ACR Classification of Functional Status in RA.
4. Active disease as defined by:
a. Swollen joint count of =4 (66 joint count) and tender joint count of =4 (68 joint count) at screening and at day 1.
AND
b. DAS28(CRP) =3.2 at screening.
AND
c. CRP =3.0 mg/L.
5. Signs of inflammation such as synovitis in the MRI scan of the most affected hand.
6. Must be currently taking MTX (15 25 mg weekly) (oral/injected) for at least 12 weeks before screening, with no change in route of administration, with a stable and tolerated dose for =4 weeks prior to Day 1. A stable dose of MTX =7.5 mg/week is acceptable, if the MTX dose has been reduced for reasons of documented intolerance to MTX, e.g. hepatic or hematologic toxicity, or per local requirement.
7. Body weight =45 kg.
8. Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria detailed in Appendix 12.2 of the protocol.
9. Capable of giving signed informed consent as described in Section 7.2 of the protocol which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
10. Willing to continue or initiate treatment with oral folic acid (at least 5 mg/week) or equivalent and be treated during the entire study (mandatory co medication for MTX treatment).
11. DLCO =60% predicted; FEV1 =70% predicted.
12. No evidence of active or latent infection with TB
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion criteria:
1.Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding.
2.History of other inflammatory rheumatologic or autoimmune disorders, other than Sjögren's syndrome secondary to RA.
3.History of any respiratory disease which would compromise subject safety or the ability of the subject to complete the study
4.Clinically significant persistent cough or clinically significant or unstable dyspnea that is unexplained.
5.QT interval corrected for heart rate (QTc) >450msec or QTc >480 msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF).
6.Liver function tests: alanine aminotransferase (ALT) >1.5x upper limit of normal (ULN); aspartate transaminase (AST) >1.5 upper limit of normal; alkaline phosphatase and bilirubin =1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
7.Current active liver or biliary disease
8.Significant unstable or uncontrolled acute or chronic disease, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, psychiatric, malignancy, endocrinologic or infectious diseases, which could confound the results of the study or put the subject at undue risk.
9.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.
10.Kidney disease: Current or history of renal disease, or estimated creatinine clearance <60 mL/min/1.73m^2 or serum creatinine >1.5xULN at screening.
11.Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.
12.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.
13.Active infections, or history of recurrent infections or has required management of acute or chronic infections
14.A vaccination 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.
15.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.
16.Contraindication to MRI scanning
17.Use of prohibited medications:
•Prior to AND throughout the study: Any conventional DMARDs other than MTX must be withdrawn at least 2 weeks prior to Day 1.
18.Tofacitinib must be discontinued at least 2 weeks prior to Day 1.
19.Corticosteroids:
•Any IM, IV or intra articular (IA) corticosteroids within 8 weeks of Day 1.
•Oral corticosteroids
•Any treatment with >10 mg/day dose oral prednisolone (or equivalent) within 28 days of Day 1.
•New oral corticosteroid or changes in corticosteroid dose within the 28 days prior to Day 1. (New topical steroids and immunosuppressive agents are permitted).
20.Non steroidal anti inflammatory drugs (NSAIDs):
•New or change in dose of NSAID within 14 days of Day 1.
21.Any prior investigational treatment must be discontinued for at least
4 weeks or 5 half lives, whichever is longer, prior to Day 1.
22.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.
23.History of sensitivity to any of the study treatments, or components thereof or a history of drug

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 19.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Code: GSK3196165
Pharmaceutical Form: Solution for injection
INN or Proposed INN: INN not available
CAS Number: 1638332-55-4
Current Sponsor code: GSK3196165
Other descriptive name: Anti human granulocyte-macrophage colony-stimulating factor (GM-CSF) monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Changes from baseline in exploratory biomarkers

Main Objective: The main objectives of this study are to explore the activity of GM-CSF signaling pathway characterized by exploratory biomarkers in subjects with RA, the impact of GSK3196165 therapy, and whether there are any differences in this GM-CSF signaling pathway between subjects with early RA or established RA.

Secondary Objective: - To evaluate the safety and tolerability of GSK3196165 in subjects with RA.
- To evaluate the impact of GSK3196165 on inflammatory structural joint damage in the hand/wrist using MRI.

Timepoint(s) of evaluation of this end point: At Week 12

Secondary Outcome(s)

Secondary end point(s): - Incidence of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs).
- Immunogenicity (anti drug antibodies [ADAs])
- Change from baseline in synovitis, osteitis and erosion as assessed by Outcome Measures in Rheumatology (OMERACT) rheumatoid arthritis MRI scoring system (RAMRIS) and rheumatoid arthritis MRI quantitative score (RAMRIQ) in the most affected hand/wrist.

Timepoint(s) of evaluation of this end point: At various time points up to Week 22 as defined in the protocol

Secondary ID(s)

RENAISSANCE

205180

Source(s) of Monetary Support

GlaxoSmithKline Research & Development Limited