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Arthritis, RheumatoidPhase 2NCT00674635

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

A Phase 2 study testing GSK3152314A in people with Arthritis, Rheumatoid, run by GlaxoSmithKline at 19 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Arthritis, Rheumatoid
What is being tested?
GSK3152314A
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
135 participants
Where
19 sitesin 5 countries
Study dates
Apr 2008to Dec 2010
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

19 sites in 5 countries.

19 sites in 5 countries

Russia5 sites

  • GSK Investigational Site

    Moscow, 115522

  • GSK Investigational Site

    Moscow, 129327

  • GSK Investigational Site

    Novosibirsk, 630117

  • GSK Investigational Site

    Smolensk, 214018

  • GSK Investigational Site

    Yaroslavl, 150062

Other trials in Russia

Ukraine5 sites

  • GSK Investigational Site

    Donetsk, 83114

  • GSK Investigational Site

    Kyiv, 03103

  • GSK Investigational Site

    Kyiv, 03680

  • GSK Investigational Site

    Lviv, 79013

  • GSK Investigational Site

    Zaporizhzhya, 69035

Other trials in Ukraine

Australia3 sites

  • GSK Investigational Site

    Heidelberg, Victoria, 3084

  • GSK Investigational Site

    Melbourne, Victoria, VIC 30004

  • GSK Investigational Site

    Woolloongabba, Queensland, 4102

Other trials in Australia

New Zealand3 sites

  • GSK Investigational Site

    Christchurch, 8011

  • GSK Investigational Site

    Hamilton, 2001

  • GSK Investigational Site

    Wellington, 6035

Other trials in New Zealand

Serbia3 sites

  • GSK Investigational Site

    Belgrade, 11000

  • GSK Investigational Site

    Belgrade, 11080

  • GSK Investigational Site

    Niška Banja, 18205

Other trials in Serbia

About this study

Official 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)

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.

Being tested
GSK3152314A, Placebo
Keywords
adaptive study,, DAS28,, monoclonal antibody, GSK315234A;, rheumatoid arthritis,
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK3152314ADrug

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

  • PlaceboDrug

    matching placebo

Study groups in NCT00674635
Study groupRoleWhat they receive
PlaceboPlacebo comparatormatching placebo
Receives: Drug: Placebo
GSK315234AActive comparatorPart A single IV dose; Part B 3 repeat IV dose at Day 1, Day 28 and Day 56; Part C single SC dose
Receives: Drug: GSK3152314A

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. • 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.

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

  2. • 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

    Measured: Part A total of 150 days

  3. • 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)

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

Secondary outcomes (18)

  1. Weighted mean DAS28 after single and repeat intravenous doses

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

  2. 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

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

  3. DAS28 and EULAR response criteria after single and repeat intravenous doses

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

  4. ACR20/ACR50/ACR70 response after single and repeat intravenous doses

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

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

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

  6. Number of tender/painful joints assessed using 28-joint counts.

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

  7. Subject's pain assessment

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

  8. Physician's global assessment of arthritis condition.

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

  9. Patients' global assessment of arthritis condition.

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

  10. Functional disability index (Health Assessment Questionnaire)

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

  11. C-reactive Protein (CRP).

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

  12. ESR

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

  13. Global Fatigue Index

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

  14. HAQ disability index

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

  15. Pharmacodynamic biomarkers after single and repeat intravenous doses:

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

  16. Characteristic AUC50 and EC50 for clinical endpoint changes with plasma exposure model, as assessed by sigmoid Emax and indirect response PK/PD models.

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

  17. Immunogenicity (Human anti-GSK315234A antibodies)

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

  18. • 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

    Measured: Part C total of 180days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2008 (estimated)
  2. Study startApr 2008
  3. Primary completionDec 2010
  4. Study completionDec 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
135 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00674635
Sponsor's protocol ID
104972
Status last verified
Nov 2016
First submitted
22 Apr 2008
Last updated
1 Dec 2016
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • 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.

    PubMed 24286335

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK3152314A in people with Arthritis, Rheumatoid, run by GlaxoSmithKline at 19 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Russia, Ukraine, Australia, New Zealand, Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

• 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. (time frame: Part A total of 150Days; Part B total of 236 days and Part C total of 180 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00674635, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2016.

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