Rheumatoid ArthritisPhase 2NCT02862574
Andecaliximab as Add-On Therapy to a Tumor Necrosis Factor Inhibitor and Methotrexate Regimen in Adults With Moderately to Severely Active Rheumatoid Arthritis
A Phase 2 study testing Andecaliximab, Methotrexate and TNF Inhibitor in people with Rheumatoid Arthritis, run by Gilead Sciences at 8 sites in United States.
Trial summary
The primary objective of this study is to evaluate the efficacy of andecaliximab (GS-5745) versus placebo as an add-on therapy to a tumor necrosis factor (TNF) inhibitor and methotrexate in adults with moderate to severe rheumatoid arthritis (RA). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Andecaliximab, Methotrexate and TNF Inhibitor
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 8 sitesUnited States
- Study dates
- 15 Dec 2016to 7 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of RA (according to the 2010 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria) confirmed at screening
- Must have taken oral or parenteral methotrexate (MTX) dosed from 7.5 to 25 mg/week continuously for at least 12 weeks and tolerated this medication, with at least 6 weeks of stable dose (defined as no change in prescription) prior to first dose of study drug
- Individuals on MTX may also be on concurrent chloroquine or hydroxychloroquine at a stable dose (defined as no change in prescription) for at least 4 week prior to Baseline; if so, they should plan to continue this medication for the duration of the study
- Must have an inadequate response to ≥ 12 weeks of ongoing treatment with an approved, stable subcutaneous (SC) formulation of TNF inhibitor (adalimumab, certolizumab pegol, etanercept, or golimumab), or marketed SC biosimilar TNF inhibitor with at least 6 weeks of stable dose (defined as no change in prescription), defined as: must have a DAS28(CRP) > 3.2 at screening AND must have ≥ 3 swollen and ≥ 3 tender joints (using the DAS28 joint counts) at screening and at baseline (do not need to be the same joints)
- Non-steroidal anti-inflammatory drugs (NSAIDs) and/or oral corticosteroids (≤ 10 mg prednisone/day or equivalent) at a stable dose (defined as no change in prescription) for ≥ 4 weeks prior to baseline are allowed and throughout the blinded period of the study. PRN NSAID for indications other than RA are also allowed. (PRN means "pro re nata" or when necessary)
- Tuberculosis (TB) Screening: Must meet either a. or b.:
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- A negative history of TB infection and a negative QuantiFERON® TB-Gold In-Tube test and chest x-ray results. (QuantiFERON® tests with inconclusive results may be repeated one time. If the repeat result is also inconclusive, the individual will be excluded from the study).
- OR,
- Individuals with a history of latent TB treated with a full course of prophylaxis as per local guidelines are allowed per investigator judgment. It is the responsibility of the investigator to verify the adequacy of previous treatment and to provide appropriate documentation. In these cases, no QuantiFERON® test need be obtained. In addition, these cases must be approved by the medical monitor prior to enrollment. (Any new diagnosis of latent TB or prior untreated /partially treated latent TB in NOT allowed (ie, individuals who require prophylactic therapy for TB during the study). Any prior history of active TB [regardless of treatment] is exclusionary).
- A negative chest x-ray (views per local guidelines) for active TB or other lung disease at screening; or a chest x-ray within 90 days of screening if films or report are available for investigator review
Who cannot join
- Current treatment with any other disease modifying anti-rheumatic drug (DMARD) other than MTX, chloroquine or hydroxychloroquine, OR current treatment with other immune modulating/suppressive non-biologic and biologic medications as described in the study protocol
- Intraarticular corticosteroid injection of any joint within 4 weeks of baseline
- Any infection requiring oral antimicrobial therapy within 2 weeks prior to baseline
- Current inflammatory joint disease, other than RA, such as gout, reactive arthritis, psoriatic arthritis, seronegative spondylarthritis, or Lyme disease, OR other current autoimmune diseases such as: systemic lupus erythematosus (SLE), inflammatory bowel disease, fibromyalgia, polymyalgia rheumatica, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome that would interfere with the evaluation of RA or require protocol prohibited medication (individuals with Sjogren's syndrome or controlled thyroiditis as defined by the investigator are not excluded)
- Active systemic involvement secondary to RA such as vasculitis or Felty's syndrome
- History of any of the following within 12 months of baseline:
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- infection requiring parenteral antibiotics or hospitalization
- any life-threatening infection
- sepsis
- The results of the following laboratory tests performed at the central laboratory at screening meet any of the criteria below:
- Hemoglobin < 8.0 g/dL (International System of Units (SI): < 80 g/L)
- White blood cells < 3.0 x 10^3 cells/mm^3 (SI: < 3.0 x 10^9 cells/L)
- Neutrophils < 1.5 x 10^3 cells/mm^3 (SI: < 1.5 x 10^9 cells/L)
- Lymphocytes < 0.5 x 10^3 cells/mm^3 (SI: < 0.5 x 10^9 cells/L)
- Platelets < 100 x 10^3 cells/mm^3 (SI: < 100 x 10^9 cells/L)
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2 x upper limit of normal (ULN)
- Total bilirubin level ≥ 2 x ULN unless the individual has been diagnosed with Gilbert's disease and this is clearly documented
- Estimated glomerular filtration rate < 40 mL/min/1.73 m^2 based on the Modification of Diet in Renal Disease (MDRD) formula
- Positive HIV serology during screening
- Evidence of active Hepatitis B Virus (HBV) infection
- Evidence of active Hepatitis C Virus (HCV) infection
- Any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the individual's participation in the study
- Malignancy or a history of malignancy or lymphoproliferative disorder within 10 years of screening with the following exceptions:
- Carcinoma in situ of the cervix that has been successfully treated
- Adequately treated basal or squamous cell cancer that has been successfully treated
- Note: Other protocol defined inclusion/exclusion criteria may apply.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Albuquerque Center for Rheumatology
Albuquerque, New Mexico, 87102
Tekton Research
Austin, Texas, 78728
Omega Research Consultants, LLC
DeBary, Florida, 32713
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
G. Timothy Kelly, MD
Las Vegas, Nevada, 89128
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Stanford University
Palo Alto, California, 94304
Accurate Clinical Research
San Antonio, Texas, 78229
About this study
Official title: Evaluation of the Efficacy and Safety of GS-5745 as Add-On Therapy to a Tumor Necrosis Factor Inhibitor and Methotrexate Regimen in Subjects With Moderate to Severe Rheumatoid Arthritis
The primary objective of this study is to evaluate the efficacy of andecaliximab (GS-5745) versus placebo as an add-on therapy to a tumor necrosis factor (TNF) inhibitor and methotrexate in adults with moderate to severe rheumatoid arthritis (RA).
- Conditions
- Rheumatoid Arthritis
- Being tested
- Andecaliximab, Placebo, Methotrexate, TNF Inhibitor
- Keywords
- Rheumatoid Arthritis, Tumor Necrosis Factor Inhibitor, TNF-IR, Methotrexate
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AndecaliximabDrug
Also called GS-5745
Administered via subcutaneous injection once weekly
PlaceboDrug
Administered via subcutaneous injection once weekly
MethotrexateDrug
Administered orally weekly as part of the participant's current treatment regimen
TNF InhibitorDrug
An approved stable subcutaneous formulation of one of the following TNF inhibitors may include adalimumab, certolizumab, etanercept, or golimumab.
| Study group | Role | What they receive |
|---|---|---|
| Andecaliximab 300 mg | Experimental | Andecaliximab 300 mg for 12 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate. Receives: Drug: Andecaliximab; Drug: Methotrexate; Drug: TNF Inhibitor |
| Andecaliximab 150 mg | Experimental | Andecaliximab 150 mg + placebo for 12 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate. Receives: Drug: Andecaliximab; Drug: Placebo; Drug: Methotrexate; Drug: TNF Inhibitor |
| Placebo | Placebo comparator | Placebo weekly for 12 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate. Receives: Drug: Placebo; Drug: Methotrexate; Drug: TNF Inhibitor |
| Open-Label Extension | Experimental | On the Week 12 visit, eligible participants may choose to participate in the open-label portion of the study to receive open-label andecaliximab 300 mg for 52 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate. Receives: Drug: Andecaliximab; Drug: Methotrexate; Drug: TNF Inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in DAS28(CRP) at Week 12
The DAS28 score is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), Patient's Global Assessment of Disease Activity (visual analog scale: 0 = no disease activity to 100 = maximum disease activity), and CRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.
Measured: Baseline; Week 12
Secondary outcomes (3)
Percentage of Participants That Achieve DAS28(CRP) ≤ 3.2 at Week 12
The DAS28 score is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), Patient's Global Assessment of Disease Activity (visual analog scale: 0 = no disease activity to 100 = maximum disease activity), and CRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.
Measured: Week 12
Percentage of Participants That Achieve DAS28(CRP) < 2.6 at Week 12
The DAS28 score is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), Patient's Global Assessment of Disease Activity (visual analog scale: 0 = no disease activity to 100 = maximum disease activity), and CRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.
Measured: Week 12
Plasma Concentration of Andecaliximab
The plasma concentrations of andecaliximab were not collected and were not analyzed.
Measured: Day 4 or 6 (± 1 day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2016 (estimated)
- Study start15 Dec 2016
- Primary completion26 Jun 2017
- Study completion7 Aug 2017
Why it stopped: Study was terminated by sponsor and decision was not due to any safety signals.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02862574
- Sponsor's protocol ID
- GS-US-373-1499
- Other IDs
- 2016-000897-39, 2016
- Status last verified
- May 2018
- First submitted
- 8 Aug 2016
- Last updated
- 27 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy and Safety of GS-5745 as Add-On Therapy to a Tumor Necrosis Factor Inhibitor and Methotrexate Regimen in Subjects With Moderate to Severe Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT02862574
- Acronym / sponsor ID
- GS-US-373-1499
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, Tumor Necrosis Factor Inhibitor, TNF-IR, Methotrexate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated by sponsor and decision was not due to any safety signals.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 15 Dec 2016 (actual)
- Primary completion
- 26 Jun 2017 (actual)
- Study completion
- 7 Aug 2017 (actual)
- First posted
- 11 Aug 2016 (estimated)
- Results
- Posted 27 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the efficacy of andecaliximab (GS-5745) versus placebo as an add-on therapy to a tumor necrosis factor (TNF) inhibitor and methotrexate in adults with moderate to severe rheumatoid arthritis (RA).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Andecaliximab 300 mg | Experimental | Drug: Andecaliximab, Drug: Methotrexate, Drug: TNF InhibitorAndecaliximab 300 mg for 12 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate. |
| Andecaliximab 150 mg | Experimental | Drug: Andecaliximab, Drug: Placebo, Drug: Methotrexate, Drug: TNF InhibitorAndecaliximab 150 mg + placebo for 12 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate. |
| Placebo | Placebo comparator | Drug: Placebo, Drug: Methotrexate, Drug: TNF InhibitorPlacebo weekly for 12 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate. |
| Open-Label Extension | Experimental | Drug: Andecaliximab, Drug: Methotrexate, Drug: TNF InhibitorOn the Week 12 visit, eligible participants may choose to participate in the open-label portion of the study to receive open-label andecaliximab 300 mg for 52 weeks, in addition to their current regimen of a TNF inhibitor and methotrexate. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Diagnosis of RA (according to the 2010 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria) confirmed at screening
- Must have taken oral or parenteral methotrexate (MTX) dosed from 7.5 to 25 mg/week continuously for at least 12 weeks and tolerated this medication, with at least 6 weeks of stable dose (defined as no change in prescription) prior to first dose of study drug
- Individuals on MTX may also be on concurrent chloroquine or hydroxychloroquine at a stable dose (defined as no change in prescription) for at least 4 week prior to Baseline; if so, they should plan to continue this medication for the duration of the study
- Must have an inadequate response to ≥ 12 weeks of ongoing treatment with an approved, stable subcutaneous (SC) formulation of TNF inhibitor (adalimumab, certolizumab pegol, etanercept, or golimumab), or marketed SC biosimilar TNF inhibitor with at least 6 weeks of stable dose (defined as no change in prescription), defined as: must have a DAS28(CRP) > 3.2 at screening AND must have ≥ 3 swollen and ≥ 3 tender joints (using the DAS28 joint counts) at screening and at baseline (do not need to be the same joints)
- Non-steroidal anti-inflammatory drugs (NSAIDs) and/or oral corticosteroids (≤ 10 mg prednisone/day or equivalent) at a stable dose (defined as no change in prescription) for ≥ 4 weeks prior to baseline are allowed and throughout the blinded period of the study. PRN NSAID for indications other than RA are also allowed. (PRN means "pro re nata" or when necessary)
Key exclusion criteria (26 listed)
- Current treatment with any other disease modifying anti-rheumatic drug (DMARD) other than MTX, chloroquine or hydroxychloroquine, OR current treatment with other immune modulating/suppressive non-biologic and biologic medications as described in the study protocol
- Intraarticular corticosteroid injection of any joint within 4 weeks of baseline
- Any infection requiring oral antimicrobial therapy within 2 weeks prior to baseline
- Current inflammatory joint disease, other than RA, such as gout, reactive arthritis, psoriatic arthritis, seronegative spondylarthritis, or Lyme disease, OR other current autoimmune diseases such as: systemic lupus erythematosus (SLE), inflammatory bowel disease, fibromyalgia, polymyalgia rheumatica, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome that would interfere with the evaluation of RA or require protocol prohibited medication (individuals with Sjogren's syndrome or controlled thyroiditis as defined by the investigator are not excluded)
- Active systemic involvement secondary to RA such as vasculitis or Felty's syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AndecaliximabAlso: GS-5745Administered via subcutaneous injection once weekly | Drug | Andecaliximab 150 mg, Andecaliximab 300 mg, Open-Label Extension |
| PlaceboAdministered via subcutaneous injection once weekly | Drug | Andecaliximab 150 mg, Placebo |
| MethotrexateAdministered orally weekly as part of the participant's current treatment regimen | Drug | Andecaliximab 150 mg, Andecaliximab 300 mg, Open-Label Extension, Placebo |
| TNF InhibitorAn approved stable subcutaneous formulation of one of the following TNF inhibitors may include adalimumab, certolizumab, etanercept, or golimumab. | Drug | Andecaliximab 150 mg, Andecaliximab 300 mg, Open-Label Extension, Placebo |
Primary outcome
Change From Baseline in DAS28(CRP) at Week 12
Time frame: Baseline; Week 12
The DAS28 score is a measure of the participant's disease activity calculated using the tender joint counts (28 joints), swollen joint counts (28 joints), Patient's Global Assessment of Disease Activity (visual analog scale: 0 = no disease activity to 100 = maximum disease activity), and CRP for a total possible score of 1 to 9.4. Higher values indicate higher disease activity. A negative change from baseline indicates improvement.
3 secondary outcomes
Percentage of Participants That Achieve DAS28(CRP) ≤ 3.2 at Week 12
Time frame: Week 12
Percentage of Participants That Achieve DAS28(CRP) < 2.6 at Week 12
Time frame: Week 12
Plasma Concentration of Andecaliximab
Time frame: Day 4 or 6 (± 1 day)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Andecaliximab, Methotrexate and TNF Inhibitor in people with Rheumatoid Arthritis, run by Gilead Sciences at 8 sites in United States.
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 10 inclusion and 26 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: stopped early, as of the sponsor's last update on 27 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. 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?
Yes. Results are posted in the registry (first posted 27 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline in DAS28(CRP) at Week 12 (time frame: Baseline; Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Jun 2018.