Phase II Study Evaluating the Safety and Efficacy of GSK315234A in Patients With Rheumatoid Arthritis

NCT00674635 | Completed Phase 2

• 1 other identifier: 104972
• Study Type: interventional
• Target: 135
• Locations: 5 countries
• Sites: 19

Brief Summary

This is a randomized, double-blinded, placebo-controlled adaptive, dose finding study to investigate the safety, tolerability, PK, PD and efficacy of single and repeat intravenous infusions of GSK315243A in patients with active rheumatoid arthritis. The study is divided into 2 parts: Part A is an adaptive, dose finding phase which will provide safety, tolerability, PK and PD on single intravenous infusions. Part B is a repeat dose phase which will provide safety, tolerability, PK, PD and efficacy following repeat intravenous infusions of a selected dose level.

Conditions

Arthritis, Rheumatoid

Keywords

adaptive study,; DAS28,; monoclonal antibody; GSK315234A;; rheumatoid arthritis,

Outcome Measures

Primary Outcomes (3)

• • To assess the safety and tolerability of GSK315234A after single and repeat intravenous infusions in subjects with active rheumatoid arthritis on a background of methotrexate.

  safety assessment includes AEs, vital signs, ECG, clinical laboratory tests.

  Part A total of 150Days; Part B total of 236 days and Part C total of 180 days

• • To assess the effect of GSK315234A on disease activity [as defined by Disease Activity Score (DAS) 28 score] on Day 28 after a single intravenous infusion

  DAS28 at Day 28 and DAS28 at Day 56

  Part A total of 150 days

• • To assess the effect of GSK315234A on disease activity [as defined by Disease Activity Score (DAS) 28 score] on Day 56 in subjects with active rheumatoid arthritis on a background of methotrexate (Part B and Part C).

  DAS28 scores on Day 56 (Part B and C)

  Part B total of 236 days and Part C total of 180 days

Secondary Outcomes (18)

• Weighted mean DAS28 after single and repeat intravenous doses

  Part A total of 150Days; Part B total of 236 days and Part C total of 180 days

• Plasma PK parameters of GSK315234A after single and repeat intravenous doses including free, and bound GSK315234A (serum) concentrations, AUC(0-¥), Cmax, clearance, volume of distribution and accumulation ratio

  Part A total of 150Days; Part B total of 236 days and Part C total of 180 days

• DAS28 and EULAR response criteria after single and repeat intravenous doses

  Part A total of 150Days; Part B total of 236 days and Part C total of 180 days

• ACR20/ACR50/ACR70 response after single and repeat intravenous doses

  Part A total of 150Days; Part B total of 236 days and Part C total of 180 days

• Number of swollen joints assessed using 28-joint counts.

  Part A total of 150Days; Part B total of 236 days and Part C total of 180 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

matching placebo

Drug: Placebo

GSK315234A

ACTIVE COMPARATOR

Part A single IV dose; Part B 3 repeat IV dose at Day 1, Day 28 and Day 56; Part C single SC dose

Drug: GSK3152314A

Interventions

GSK3152314A DRUG

Part A single IV dose; Part B 3 repeat IV dose at Day 1, Day 28 and Day 56; Part C single SC dose

GSK315234A

Placebo DRUG

matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females between 18 and 75 years of age, inclusive.
• All subjects must use acceptable contraception (as defined in the study restriction section) to ensure that no pregnancies occur during the course of the study and for at least 12 weeks after dosing for males and for 32 weeks after dosing for females (see Section 7.1 on contraception for more details).
• Body mass index within the range 18.5 - 35 kg/m2 inclusive, in addition to a weight range of 55 - 95kg.
• The subject must be capable of giving informed consent and can comply with the study requirements and timetable.
• The subject must have a diagnosis of RA according to the revised 1987 criteria of the American College of Rheumatology (ACR) (see Appendix 2).
• The subject must have a DAS28 disease activity score of greater than 4.2 at screening and pre-dose.
• The subject must have a CRP serum level of \>/0.5mg/dl or an ESR level 28mm/hour at screening and pre-dose
• The subject has NOT received any biological therapy in the past, including biologicals for the treatment of rheumatoid arthritis
• The subject must have liver function tests including alanine transaminase (ALT) and aspartate transaminase (AST) within 1.5 times the upper limit of normal (ULN) and alkaline phosphatase (ALP) within 3 times ULN at screening. The patient must also have total bilirubin within the ULN at screening.
• The subject must have received at least 3 months of methotrexate and must be on a stable dose of methotrexate (up to 25 mg/week) for at least 8 weeks prior to screening and be willing to remain on this dose throughout the study.
• If sulfasalazine is being taken in addition to methotrexate, the subject must be on a stable dose for at least 4 weeks prior to screening and be willing to remain on this dose throughout the study.
• If hydroxychloroquine or chloroquine is being taken in addition to methotrexate, the subject must be on a stable dose for at least 3 months prior to screening and be willing to remain on this dose throughout the study.
• Those subjects on other oral anti-rheumatic therapies, which may include Non Steroidal Anti Inflammatory Drugs (NSAIDs), COX-2 inhibitors, oral glucocorticoids e.g. prednisolone (£10mg/day) must be on stable dosing regimens for at least 4 weeks prior to screening and be willing to remain on this regime throughout the study. Subjects receiving intramuscular glucocorticoids e.g methylprednisolone (£120 mg/month) must be on a stable dosing regimen for at least 3 months prior to screening and be willing to remain on this regimen throughout the study.
• The subject must be on a stable dose of folate supplements (5 mg/week) for at least 4 weeks prior to do

You may not qualify if:

• Any clinically relevant abnormality identified on the screening medical assessment, laboratory examination (e.g. haematology parameter outside the normal limits), or ECG (12 Lead or Holter).
• The subject has a positive Hepatitis B surface antigen or Hepatitis C antibody result at screening.
• The subject has a history of elevated liver function tests on more than one occasion (ALT, AST and ALP \> 3 x Upper Limit of Normal (ULN); total bilirubin \> 1.5 x ULN) in the past 6 months.
• Previous exposure or past infection caused by Mycobacterium tuberculosis
• The subject has an acute infection.
• The subject has a history of repeated, chronic or opportunistic infections that, in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as a participant in this trial.
• The subject has a history of malignancy, except for surgically cured basal cell carcinoma or females with cured cervical carcinoma (\> 2 yrs prior).
• The subject has a history of human immunodeficiency virus (HIV) or other immunodeficiency disease.
• The subject whose calculated creatinine clearance is less than 50ml/min
• The subject has significant cardiac, pulmonary, metabolic, renal, hepatic or gastrointestinal conditions that, in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as a participant in this trial.
• The subject has taken cyclosporine, leflonomide, cyclophosphamide or azathioprine within 1 month of screening. Subjects that have taken cyclosporine, leflonomide, cyclophosphamide or azathioprine in the past must have recovered from all drug related adverse events.
• The subject has taken gold salts or d-penicillamine within 1 month prior to screening. Subjects that have taken gold salts or d-penicillamine in the past must have recovered from all drug related adverse events.
• The subject has received intra-articular glucocorticoids within 1 month of screening.
• Recent history of bleeding disorders, anaemia, peptic ulcer disease, haematemesis or gastrointestinal bleeding
• Subjects with a history of haematological disease or acquired platelet disorders, including drug-induced thrombocytopaenia, acute idiopathic thrombocytopaenia or von Willebrand's disease.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (19)

GSK Investigational Site

Woolloongabba, Queensland, 4102, Australia

Location

GSK Investigational Site

Heidelberg, Victoria, 3084, Australia

Location

GSK Investigational Site

Melbourne, Victoria, VIC 30004, Australia

Location

GSK Investigational Site

Christchurch, 8011, New Zealand

Location

GSK Investigational Site

Hamilton, 2001, New Zealand

Location

GSK Investigational Site

Wellington, 6035, New Zealand

Location

GSK Investigational Site

Moscow, 115522, Russia

Location

GSK Investigational Site

Moscow, 129327, Russia

Location

GSK Investigational Site

Novosibirsk, 630117, Russia

Location

GSK Investigational Site

Smolensk, 214018, Russia

Location

GSK Investigational Site

Yaroslavl, 150062, Russia

Location

GSK Investigational Site

Belgrade, 11000, Serbia

Location

GSK Investigational Site

Belgrade, 11080, Serbia

Location

GSK Investigational Site

Niška Banja, 18205, Serbia

Location

GSK Investigational Site

Donetsk, 83114, Ukraine

Location

GSK Investigational Site

Kyiv, 03103, Ukraine

Location

GSK Investigational Site

Kyiv, 03680, Ukraine

Location

GSK Investigational Site

Lviv, 79013, Ukraine

Location

GSK Investigational Site

Zaporizhzhya, 69035, Ukraine

Location

Related Publications (1)

• Choy EH, Bendit M, McAleer D, Liu F, Feeney M, Brett S, Zamuner S, Campanile A, Toso J. Safety, tolerability, pharmacokinetics and pharmacodynamics of an anti- oncostatin M monoclonal antibody in rheumatoid arthritis: results from phase II randomized, placebo-controlled trials. Arthritis Res Ther. 2013 Sep 24;15(5):R132. doi: 10.1186/ar4312.

  PMID: 24286335 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2008
• First Posted: May 8, 2008
• Study Start: April 1, 2008
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: December 1, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

UA (5); RU (5); SE (3); AU (3); NZ (3)