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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00674635




Registration number
NCT00674635
Ethics application status
Date submitted
22/04/2008
Date registered
8/05/2008

Titles & IDs
Public title
Phase II Study Evaluating the Safety and Efficacy of GSK315234A in Patients With Rheumatoid Arthritis
Scientific title
A Randomized, Double-blind, Placebo-controlled, Bayesian Adaptive Dose Finding Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Intravenous Infusions GSK315234A in Patients With Active Rheumatoid Arthritis (RA)
Secondary ID [1] 0 0
104972
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arthritis, Rheumatoid 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK3152314A
Treatment: Drugs - Placebo

Placebo comparator: Placebo - matching placebo

Active comparator: GSK315234A - Part A single IV dose; Part B 3 repeat IV dose at Day 1, Day 28 and Day 56; Part C single SC dose


Treatment: Drugs: GSK3152314A
Part A single IV dose; Part B 3 repeat IV dose at Day 1, Day 28 and Day 56; Part C single SC dose

Treatment: Drugs: Placebo
matching placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
• 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.
Timepoint [1] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Primary outcome [2] 0 0
• 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
Timepoint [2] 0 0
Part A total of 150 days
Primary outcome [3] 0 0
• 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).
Timepoint [3] 0 0
Part B total of 236 days and Part C total of 180 days
Secondary outcome [1] 0 0
Weighted mean DAS28 after single and repeat intravenous doses
Timepoint [1] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [3] 0 0
DAS28 and EULAR response criteria after single and repeat intravenous doses
Timepoint [3] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [4] 0 0
ACR20/ACR50/ACR70 response after single and repeat intravenous doses
Timepoint [4] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [5] 0 0
Number of swollen joints assessed using 28-joint counts.
Timepoint [5] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [6] 0 0
Number of tender/painful joints assessed using 28-joint counts.
Timepoint [6] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [7] 0 0
Subject's pain assessment
Timepoint [7] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [8] 0 0
Physician's global assessment of arthritis condition.
Timepoint [8] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [9] 0 0
Patients' global assessment of arthritis condition.
Timepoint [9] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [10] 0 0
Functional disability index (Health Assessment Questionnaire)
Timepoint [10] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [11] 0 0
C-reactive Protein (CRP).
Timepoint [11] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [12] 0 0
ESR
Timepoint [12] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [13] 0 0
Global Fatigue Index
Timepoint [13] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [14] 0 0
HAQ disability index
Timepoint [14] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [15] 0 0
Pharmacodynamic biomarkers after single and repeat intravenous doses:
Timepoint [15] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [16] 0 0
Characteristic AUC50 and EC50 for clinical endpoint changes with plasma exposure model, as assessed by sigmoid Emax and indirect response PK/PD models.
Timepoint [16] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [17] 0 0
Immunogenicity (Human anti-GSK315234A antibodies)
Timepoint [17] 0 0
Part A total of 150Days; Part B total of 236 days and Part C total of 180 days
Secondary outcome [18] 0 0
• To assess the relative bioavailability of GSK315234A administered subcutaneously (Part C) as compared to intravenous administration in subjects with active rheumatoid arthritis on a background of methotrexate
Timepoint [18] 0 0
Part C total of 180days

Eligibility
Key inclusion criteria
* 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.
* Subjects with a known risk of intra-cranial haemorrhage including Central Nervous System (CNS) surgery within the last 12 months, arterial vascular malformations, aneurysms, significant closed head trauma within 6 months or any other incident the investigator and/or medical monitor considers to be relevant.
* The subject has Hb <10 g/deciliter (dL) and platelet count < 150 x 109/Liter (L)
* Donation of blood in excess of 500 ml within a 56 day period prior to dosing
* An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the male subject to use a condom with spermicide in addition to having their female partner use another form of contraception such as an interuterine device (IUD), diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants of levonorgestrel or a tubal ligation if the woman could become pregnant for at least 12 weeks after dosing
* An unwillingness of female subject of child bearing potential to use adequate contraception, as defined in the study restriction section. If necessary, women of non-child bearing potential (i.e. post-menopausal or surgically sterile e.g. tubal ligation or hysterectomy or bilateral oophorectomy) will be confirmed. Postmenopausal status will be confirmed by serum follicle stimulating hormone (FSH) and oestradiol concentrations at screening. Surgical sterility will be defined as females who have had a documented hysterectomy, tubal ligation or bilateral oophorectomy.
* The subject has a history of use of drugs of abuse within 12 months prior to screening.
* History of regular alcohol consumption exceeding average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). Subjects who regularly consume more than 12 units of alcohol in a 24h period will also be excluded. 1 unit is equivalent to a half-pint (220ml) of beer/lager or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
* Positive pregnancy test or lactating at screening.
* Participation in a trial with any investigational drug within 3 months or 5 half-lives (whichever is longer) before

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2010
Sample size
Target
Accrual to date
Final
135
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Woolloongabba
Recruitment hospital [2] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [3] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
VIC 30004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch
Country [2] 0 0
New Zealand
State/province [2] 0 0
Hamilton
Country [3] 0 0
New Zealand
State/province [3] 0 0
Wellington
Country [4] 0 0
Russian Federation
State/province [4] 0 0
Moscow
Country [5] 0 0
Russian Federation
State/province [5] 0 0
Novosibirsk
Country [6] 0 0
Russian Federation
State/province [6] 0 0
Smolensk
Country [7] 0 0
Russian Federation
State/province [7] 0 0
Yaroslavl
Country [8] 0 0
Serbia
State/province [8] 0 0
Belgrade
Country [9] 0 0
Serbia
State/province [9] 0 0
Niska Banja
Country [10] 0 0
Ukraine
State/province [10] 0 0
Donetsk
Country [11] 0 0
Ukraine
State/province [11] 0 0
Kyiv
Country [12] 0 0
Ukraine
State/province [12] 0 0
Lviv
Country [13] 0 0
Ukraine
State/province [13] 0 0
Zaporizhzhya

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT00674635