Rheumatoid Arthritis (RA)Phase 3NCT03660059
A Study to Assess Safety and Efficacy of ASP015K in Participants With Rheumatoid Arthritis (RA) Who Had an Inadequate Response or Intolerance to Methotrexate (MTX)
A Phase 3 study testing Peficitinib, Plaebo and Disease-modifying antirheumatic drugs (DMARDs) in people with Rheumatoid Arthritis (RA), run by Astellas Pharma China, Inc. at 43 sites in 3 countries.
Trial summary
The purpose of this study is to verify the superiority of ASP015K in combination with MTX or with other disease-modifying antirheumatic drugs (DMARDs) over placebo in terms of efficacy in participants with rheumatoid arthritis (RA) who had an inadequate response or intolerance to MTX, as measured by the American… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis (RA)
- What is being tested?
- Peficitinib, Plaebo and Disease-modifying antirheumatic drugs (DMARDs)
- 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
- 385 participants
- Where
- 43 sitesin 3 countries
- Study dates
- 27 Sep 2018to 2 Nov 2021
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is a man or woman and considered to be an adult, according to the local legal definition, at the time of informed consent.
- Subject has RA diagnosed according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria.
- Subject did not receive the following drugs, or received the drugs with stable dosage for at least 28 days prior to the baseline (start of treatment) for RA treatment: Non-steroidal anti-inflammatory drugs (NSAIDs; excluding topical formulations), oral morphine or equivalent opioid analgesics (≤ 30 mg/day), acetaminophen, or oral corticosteroids (≤ 10 mg/day in prednisolone equivalent).
- Subject has active RA as evidenced by both of the following:
- ≥ 6 tender/painful joints (using 68-joint assessment)
- ≥ 6 swollen joints (using 66-joint assessment)
Show all 19Show fewer
- Subject has CRP > 0.50 mg/dL. The re-test of CRP will be allowed, if the subject's CRP value at the time of screening test is more than 0.30 mg/dL and also his/her most recent CRP value which was carried out up to 90 days before the date of screening test was more than 0.5 mg/dL.
- Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class I, II, or III.
- Subject has inadequate response or intolerance for MTX.
- For inadequate responder to MTX, subject has had regular use of MTX for at least 90 days prior to screening at a dose that, in accordance with local clinical practice, is considered acceptable to adequately assess clinical response. The dose of MTX must have been a stable, unchanging oral dose of 7.5 to 20 mg/week (or the equivalent injectable dose) for at least the 28 days prior to screening. Subject is able to continue stable dose of MTX from at least 28 days prior to screening until the end of the administration period of study drug.
- For subject who is intolerant of MTX, subject has had regular use of the following DMARDs, and when the following DMARDs are concomitantly administered to subject, the drugs must be administered for at least 90 days prior to screening, and must be stable from at least 28 days prior to screening until the end of the administration period of study drug.
- Hydroxychloroquine
- Salazosulfapyridine
- Gold
- D-penicillamine
- Lobenzarit
- Actarit
- Bucillamine
- Iguratimod
Who cannot join
- Subject has received a biologic DMARD within the specified period:
- Anakinra: within 28 days prior to baseline
- Etanercept: within 28 days prior to baseline
- Adalimumab, infliximab: within 56 days prior to baseline
- Golimumab, certolizumab pegol: within 70 days prior to baseline
- Abatacept, tocilizumab: within 84 days prior to baseline
Show all 60Show fewer
- Denosumab: within 150 days prior to baseline
- Rituximab: within 180 days prior to baseline
- Subject has inadequate response to at least 3 biologic DMARDs.
- Subject has received a non-biologic DMARD listed below or other drugs used in the treatment of RA within 28 days prior to baseline. Leflunomide is prohibited within 90 days prior to baseline. Alternatively, leflunomide is prohibited at least 28 days prior to baseline if washout with cholestyramine for at least 17 days is completed within 28 days prior to baseline. However, topical drugs other than those for the treatment of RA may be used concomitantly.
- Leflunomide
- Tacrolimus
- Cyclosporine
- Cyclophosphamide
- Azathioprine
- Minocycline
- Mizoribine
- Subject has received Chinese herbal medicines listed below or other herbal drugs used in the treatment of RA within 28 days prior to baseline.
- Tripterygium wilfordii
- Total glucosides of paeony
- Tsuduranine
- Subject has received tofacitinib, baricitinib or other JAK inhibitor (including other investigational drugs).
- Subject has received intra-articular, intravenous, intramuscular, or endorectal (including suppositories for anal diseases) corticosteroid within 28 days prior to baseline.
- Subject has participated in any study of ASP015K and has received ASP015K or placebo.
- Subject has received other investigational drugs within 90 days or within 5 half-lives, whichever is longer, prior to baseline.
- Subject has received plasma exchange therapy within 60 days prior to baseline.
- Subject has undergone joint drainage, has received local anesthesia and nerve block, or has received articular cartilage protectant (such as glucosamine sulfate, chondroitin sulfate these DMORD medicine) at the assessed joint within 28 days prior to baseline.
- Subject has undergone surgery and has residual effects in the assessed joints or is scheduled to undergo surgery that may affect the study evaluation of the assessed joints.
- Subject is diagnosed as inflammatory arthritis (psoriatic arthritis, ankylosing spondylitis, SLE, sarcoidosis, etc.) other than RA.
- Subject has any of the following laboratory values:
- Hemoglobin < 9.0 g/dL
- Absolute neutrophil count < 1000/μL
- Absolute lymphocyte count < 800/μL
- Platelet count < 75000/μL
- Alanine aminotransferase (ALT) ≥ 2 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≥ 2 × ULN
- Total bilirubin (TBL) ≥ 1.5 × ULN
- Estimated glomerular filtration rate (eGFR) ≤ 40 mL/min as measured by the MDRD method
- β-D-glucan > ULN
- Subject has a history of or concurrent active tuberculosis (TB). Eligibility criteria for TB are tabulated below:
- Subject meets any of the following in terms of infection except for TB:
- History of or concurrent severe herpes zoster (associated with Hunt syndrome or having ulcerative lesions) or disseminated herpes zoster
- History of multiple recurrences (at least twice) of localized herpes zoster
- Serious infection requiring hospitalization within 90 days prior to baseline
- Subject has received intravenous antibiotics within 90 days prior to baseline. (However, prophylactic antibiotics are allowed.)
- Subject with high risk of infection (e.g., subject with urinary catheter)
- Subject has a history of or concurrent interstitial pneumonia and inappropriate to participate in this study.
- Subject has a history of or concurrent malignant tumor (except for successfully treated basal cell carcinoma).
- Subject has received live or live attenuated virus vaccination within 56 days prior to baseline. (Inactivated vaccines including influenza and pneumococcal vaccines are allowed.)
- Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, infectious, or autoimmune disease except for RA (excluding Sjogren's syndrome and chronic thyroiditis), or any ongoing illness which would make the subject unsuitable for the study.
- Subject has a history of clinically significant allergy. (Clinically significant allergy includes allergies such as systemic urticaria induced by specific antigens and drugs, anaphylaxis, and allergy associated with shock necessitating hospitalized treatment.)
- Subject has received medications that are CYP3A substrates with narrow therapeutic range within 14 days prior to baseline. These medications include: dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, temsirolimus, and disopyramide.
- Subject has concurrent cardiac failure, defined as New York Heart Association (NYHA) classification Class III or higher, or a history of it.
- Subject has concurrent prolonged QT syndrome or a history of it. Subject has prolonged QT interval (defined as QTc ≥ 500 msec. Subject has QTc ≥ 500 msec at retest will be excluded).
- Subject has congenital short QT syndrome or a history of it. Subject has shortened QT interval (defined as QTc < 330 msec. Subject has QTc < 330 msec at retest will be excluded).
- Subject has a history of positive HIV infection.
- Female subject is pregnant or might be pregnant, is nursing, wishes to conceive for a period running from the time informed consent is given within 60 days after end of treatment, or for whom the possibility of pregnancy cannot be ruled out as a result of the serum pregnancy test given at the time of screening.
- Male subject cannot practice at least 2 types of contraception from the time of informed consent to 90 days after end of treatment, or subject is a woman with childbearing potential who cannot practice at least 2 types of contraception from the time of informed consent to 60 days after end of treatment.
- Male subject does not agree not to donate sperm starting at informed consent and through the treatment period and for at least 90 days after final study drug administration. Female subject who do not agree not to donate ova starting at informed consent through the treatment period and for 60 days after final study drug administration.
- Subject has a history or complication of lymphatic diseases such as lymphoproliferative disorder, lymphoma, and leukemia.
Trial locations and contacts
43 sites in 3 countries.
43 sites in 3 countries
China33 sites
Site CN00048
Anhui
Site CN00045
Beijing
Site CN00054
Beijing
Site CN00050
Bengbu
Site CN00061
Changchun
Site CN00032
Changsha
Site CN00076
Chenzhou
Site CN00071
Guangdong
Site CN00016
Guangzhou
Site CN00052
Guangzhou
Site CN00063
Guangzhou
Site CN00072
Guangzhou
Site CN00058
Inner Mongolia
Site CN00074
Jieyang
Site CN00028
Jilin City
Site CN00069
Jining
Site CN00064
Jiujiang
Site CN00046
Kunming
Site CN00060
Nanjing
Site CN00070
Nanjing
Site CN00068
Ningbo
Site CN00075
Pingxiang
Site CN00066
Qingdao
Site CN00056
Shanghai
Site CN00047
Shantou
Site CN00053
Sichuan
Site CN00057
Tianjin
Site CN00062
Tianjin
Site CN00059
Wuhan
Site CN00067
Xining
Site CN00065
Xuzhou
Site CN00073
Zhengzhou
Site CN00049
Zhuzhou
South Korea5 sites
Site KR00037
Gwangju
Site KR00036
Incheon
Site KR00033
Seoul
Site KR00034
Seoul
Site KR00035
Seoul
Taiwan5 sites
Site TW00022
Taichung
Site TW00023
Taichung
Site TW00024
Taichung
Site TW00025
Taipei
Site TW00026
Taipei
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Confirmatory Study of the Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response or Intolerance to MTX
The purpose of this study is to verify the superiority of ASP015K in combination with MTX or with other disease-modifying antirheumatic drugs (DMARDs) over placebo in terms of efficacy in participants with rheumatoid arthritis (RA) who had an inadequate response or intolerance to MTX, as measured by the American College of Rheumatology (ACR) 20 response rate at Week 24.
This study will also evaluate the pharmacokinetics and safety of ASP015K as well as efficacy and safety of long-term treatment with ASP015K (52 weeks).
Read the detailed description
Participants will be randomized in a 1:1:1 ratio to the ASP015K dose-A group, ASP015K dose-B group or placebo group at Week 0.
- Conditions
- Rheumatoid Arthritis (RA)
- Being tested
- Peficitinib, Plaebo, Disease-modifying antirheumatic drugs (DMARDs)
- Keywords
- rheumatoid arthritis (RA), efficacy, ASP015K, Peficitinib, safety
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PeficitinibDrug
Also called ASP015K
Oral
PlaeboDrug
Oral
Disease-modifying antirheumatic drugs (DMARDs)Drug
As necessary concomitant medications, DMARDs listed below will be administered orally unless specified.
For subjects who are inadequate responders to methotrexate (MTX): MTX. For subjects who are intolerant of MTX: either of DMARDs listed; hydroxychloroquine, salazosulfapyridine, gold (injection or oral), D-penicillamine, lobenzarit, actarit, bucillamine and iguratimod.
| Study group | Role | What they receive |
|---|---|---|
| ASP015K 100 mg | Experimental | Participants will receive 100 milligrams (mg) of ASP015K once daily after breakfast for 52 weeks. Receives: Drug: Peficitinib; Drug: Disease-modifying antirheumatic drugs (DMARDs) |
| ASP015K 150 mg | Experimental | Participants will receive 150 mg of ASP015K once daily after breakfast for 52 weeks. Receives: Drug: Peficitinib; Drug: Disease-modifying antirheumatic drugs (DMARDs) |
| Placebo/ASP015K | Placebo comparator | Participants will receive placebo for 24 weeks, then either 100 mg or 150 mg of ASP015K for 28 weeks as determined randomly at Week 0 in advance. Receives: Drug: Peficitinib; Drug: Plaebo; Drug: Disease-modifying antirheumatic drugs (DMARDs) |
What is being measured
The primary outcome is the main question the study is designed to answer.
American College of Rheumatology (ACR)20 response rate at Week 24
The ACR20 response requires that all criteria from (1) to (3) be met compared with Week 0 (baseline); (1), Tender Joint Count (TJC) >= 20% reduction; (2), Swollen Joint Count (SJC) >= 20% reduction;(3) >= 20% improvement in three or more of the following five parameters - [1] subject's assessment of pain, [2] Subject's Global Assessment of Arthritis (SGA), [3] Physician's Global Assessment of Arthritis (PGA), [4] health assessment questionnaire-disability index (HAQ-DI), [5] acute phase reactant (C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)).
Measured: At Week 24
Secondary outcomes (33)
ACR20 response rate
The ACR20 response requires that all criteria from (1) to (3) be met compared with Week 0 (baseline); (1), Tender Joint Count (TJC) >= 20% reduction; (2), Swollen Joint Count (SJC) >= 20% reduction;(3) >= 20% improvement in three or more of the following five parameters - [1] subject's assessment of pain, [2] Subject's Global Assessment of Arthritis (SGA), [3] Physician's Global Assessment of Arthritis (PGA), [4] health assessment questionnaire-disability index (HAQ-DI), [5] acute phase reactant (C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)).
Measured: Up to Week 52
ACR50 response rate
The ACR50 response indicates a 50% improvement in all criteria used in the ACR20 assessment.
Measured: Up to Week 52
ACR70 response rate
The ACR70 response indicates a 70% improvement in all criteria used in the ACR70 assessment.
Measured: Up to Week 52
Change from baseline in disease activity score (DAS) 28-C-reactive protein (CRP) scores
DAS28-CRP will be calculated using data from TJC (28 joints), SJC (28 joints), CRP and SGA with the formula; DAS28-CRP = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 x SGA + 0.96
Measured: From baseline (Week 0) to Week 52
Change from baseline in DAS28- erythrocyte sedimentation rate (ESR) scores
DAS28-ESR will be calculated using data from TJC (28 joints), SJC (28 joints), ESR and SGA with the formula; DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x SGA
Measured: From baseline (Week 0) to Week 52
Change from baseline in Tender Joint Count (TJC) (68 joints)
The investigator/sub-investigator will examine the participant for tender joints, assessing the 68 joints and confirm the location of each tender joint.
Measured: From baseline (Week 0) to Week 52
Change from baseline in Swollen Joint Count (SJC) (66 joints)
The investigator/sub-investigator will examine the participants for swollen joints, assessing the 66 joints, where hip joints are excluded from 68 joints, and confirm the location of the swollen joints.
Measured: From baseline (Week 0) to Week 52
Percentage of participants achieving DAS28-CRP scores for remission
Percentage of participants with DAS28 scores less than 2.6.
Measured: Up to Week 52
Percentage of participants achieving DAS28-ESR scores for remission
Percentage of participants with DAS28 scores less than 2.6.
Measured: Up to Week 52
Percentage of participants achieving low disease activity by DAS28-CRP
DAS28 score exceeding 5.1 is considered high disease activity; 3.2 to 5.1, moderate disease activity; less than 3.2, low disease activity.
Measured: Up to Week 52
Percentage of participants achieving low disease activity by DAS28-ESR
DAS28 score exceeding 5.1 is considered high disease activity; 3.2 to 5.1, moderate disease activity; less than 3.2, low disease activity.
Measured: Up to Week 52
Change from baseline in CRP
CRP will be measured with blood samples.
Measured: From baseline (Week 0) to Week 52
Change from baseline in ESR
ESR will be measured with blood samples.
Measured: From baseline (Week 0) to Week 52
Percentage of participants with good European League Against Rheumatism (EULAR) response
Based on DAS28 scores and changes in DAS28 scores before and after treatment with the study drug, EULAR Response Criteria categorize response to treatment as "No response", "Moderate response," or "Good response."
Measured: Up to Week 52
Percentage of participants with good or moderate EULAR response
Based on DAS28 scores and changes in DAS28 scores before and after treatment with the study drug, EULAR Response Criteria categorize response to treatment as "No response", "Moderate response," or "Good response."
Measured: At Week 52
Percentage of participants achieving ACR/EULAR remission
If all of the following 4 parameters are fulfilled, it is defined as remission: TJC ≤ 1, SJC ≤ 1, CRP ≤ 1 mg/dL, SGA ≤ 1 cm (on a visual analog scale (VAS) of 0 - 100 mm).
Measured: At Week 52
Percentage of participants achieving Simplified Disease Activity Index (SDAI) remission (SDAI score ≤ 3.3)
SDAI score will be calculated with formula SDAI = TJC + SJC + SGA + PGA + CRP. SDAI score exceeding 26 is considered high disease activity; exceeding 11 and not greater than 26, moderate disease activity; exceeding 3.3 and not greater than 11, low disease activity.
Measured: Up to Week 52
Change from baseline in SDAI score
Change from baseline (Week 0) in SDAI score will be calculated.
Measured: From baseline (Week 0) to Week 52
Change from baseline in Physician's Global Assessment of Arthritis (PGA) (VAS)
The investigator/sub-investigator assesses the participant's disease activity on a VAS of 0 - 100 mm on the physician assessment table.
Measured: From baseline (Week 0) to Week 52
Change from baseline in SGA (VAS)
The participant assesses his/her own disease activity on a VAS of 0 - 100 mm on the questionnaire form.
Measured: From baseline (Week 0) to Week 52
Change from baseline in participant's assessment of pain (VAS)
The participant assesses his/her own pain severity on a VAS of 0 - 100 mm on the questionnaire form.
Measured: From baseline (Week 0) to Week 52
Incidence of participant withdrawal due to the lack of efficacy
Number of participants who withdraw from this study due to the lack of efficacy.
Measured: Up to Week 56
Change from baseline in health assessment questionnaire-disability index (HAQ-DI) score
The HAQ-DI measure shave eight dimensions of functional activity: pruning, dressing, rising, eating, walking, personal hygiene, reach, grip, and other routine activities. Each item has 4 degrees ranging from 0 to 3. "0" refers to "no functional difficulty", "1" to a bit of functional difficulty, "2" to very much functional difficulty, and "3" to no ability to work. HAQ-DI score 0-1 means mild to moderate functional difficulty; 1-2 means moderate to severe disability; and 2-3 means generally severe disability.
Measured: From baseline (Week 0) to Week 52
Change from baseline in Short Form Health Survey - 36 questions, version 2 (SF-36v2)® score
SF-36v2 is a validated instrument used to measure general physical and mental health status via assessment of 8 domains - physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental. The SF-36 is scored using norm-based scoring procedures and scores ranging from 0-100; higher scores represent better health-related quality of life.
Measured: From baseline (Week 0) to Week 52
Change from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) score
WPAI produces four types of scores: absenteeism (work time missed), presenteeism (impairment at work/reduced on-the-job effectiveness), work productivity loss (overall work impairment/absenteeism plus presenteeism), and activity impairment. The WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, that is, worse outcomes.
Measured: From baseline (Week 0) to Week 52
Pharmacokinetics (PK) of ASP015K in plasma: post-dose concentration
Post-dose concentration will be derived from the PK plasma samples collected.
Measured: 2 hours post-dose at either Week 4 or Week 8
PK of ASP015K in plasma: trough concentration (Ctrough)
Ctrough will be derived from the PK plasma samples collected.
Measured: Up to Week 52
Safety assessed by incidence of adverse events (AEs)
An AE is defined as any untoward medical occurrence after the signing of informed consent form in a participant administered a study drug or who has undergone study procedures and which does not necessarily have a causal relationship with this treatment.
Measured: Up to Week 56
Number of participants with vital sign abnormalities and/or AEs
Number of participants with potentially clinically significant vital sign values.
Measured: Up to Week 56
Number of participants with body weight abnormalities and/or AEs
Number of participants with potentially clinically significant body weight values.
Measured: Up to Week 56
Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs
Number of participants with potentially clinically significant 12-ECG values.
Measured: Up to Week 52
Number of participants with central ECG abnormalities and/or AEs
Number of participants with potentially clinically significant central ECG observations. Central ECG will be measured before and 2 hours after study drug administration.
Measured: Up to Week 8
Number of participants with chest radiography abnormalities and/or AEs
Number of participants with potentially clinically significant chest radiography observations.
Measured: Up to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2018
- Study start27 Sep 2018
- Primary completion1 Apr 2021
- Study completion2 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid Arthritis (RA)Studies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 385 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma China, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Astellas Pharma Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03660059
- Sponsor's protocol ID
- 015K-CL-CNA3
- Other IDs
- CTR20181199
- Status last verified
- Oct 2024
- First submitted
- 26 Aug 2018
- Last updated
- 21 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Publications
Yang Y, Li J, Liu J, Liu L, Wang Y, Hu J, Li Z, Gu J, Zhang X, Xiao Z, Zheng J, Liu L, Li Z, Wei JC. Safety and efficacy of peficitinib in Asian patients with rheumatoid arthritis who had an inadequate response or intolerance to methotrexate: results of a multicenter, randomized, double-blind, placebo-controlled phase 3 study. Lancet Reg Health West Pac. 2023 Oct 18;42:100925. doi: 10.1016/j.lanwpc.2023.100925. eCollection 2024 Jan.
PubMed 38357391
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Confirmatory Study of the Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response or Intolerance to MTX
- ClinicalTrials.gov ID
- NCT03660059
- Acronym / sponsor ID
- 015K-CL-CNA3
- Conditions
- Rheumatoid Arthritis (RA)
- Keywords
- rheumatoid arthritis (RA), efficacy, ASP015K, Peficitinib, safety
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 385 participants (actual)
- Lead sponsor
- Astellas Pharma China, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Sep 2018 (actual)
- Primary completion
- 1 Apr 2021 (actual)
- Study completion
- 2 Nov 2021 (actual)
- First posted
- 6 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to verify the superiority of ASP015K in combination with MTX or with other disease-modifying antirheumatic drugs (DMARDs) over placebo in terms of efficacy in participants with rheumatoid arthritis (RA) who had an inadequate response or intolerance to MTX, as measured by the American College of Rheumatology (ACR) 20 response rate at Week 24.
This study will also evaluate the pharmacokinetics and safety of ASP015K as well as efficacy and safety of long-term treatment with ASP015K (52 weeks).
Detailed description
Participants will be randomized in a 1:1:1 ratio to the ASP015K dose-A group, ASP015K dose-B group or placebo group at Week 0.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ASP015K 100 mg | Experimental | Drug: Peficitinib, Drug: Disease-modifying antirheumatic drugs (DMARDs)Participants will receive 100 milligrams (mg) of ASP015K once daily after breakfast for 52 weeks. |
| ASP015K 150 mg | Experimental | Drug: Peficitinib, Drug: Disease-modifying antirheumatic drugs (DMARDs)Participants will receive 150 mg of ASP015K once daily after breakfast for 52 weeks. |
| Placebo/ASP015K | Placebo comparator | Drug: Peficitinib, Drug: Plaebo, Drug: Disease-modifying antirheumatic drugs (DMARDs)Participants will receive placebo for 24 weeks, then either 100 mg or 150 mg of ASP015K for 28 weeks as determined randomly at Week 0 in advance. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Subject is a man or woman and considered to be an adult, according to the local legal definition, at the time of informed consent.
- Subject has RA diagnosed according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria.
- Subject did not receive the following drugs, or received the drugs with stable dosage for at least 28 days prior to the baseline (start of treatment) for RA treatment: Non-steroidal anti-inflammatory drugs (NSAIDs; excluding topical formulations), oral morphine or equivalent opioid analgesics (≤ 30 mg/day), acetaminophen, or oral corticosteroids (≤ 10 mg/day in prednisolone equivalent).
- Subject has active RA as evidenced by both of the following:
- Subject has CRP > 0.50 mg/dL. The re-test of CRP will be allowed, if the subject's CRP value at the time of screening test is more than 0.30 mg/dL and also his/her most recent CRP value which was carried out up to 90 days before the date of screening test was more than 0.5 mg/dL.
Key exclusion criteria (60 listed)
- Subject has received a biologic DMARD within the specified period:
- Subject has inadequate response to at least 3 biologic DMARDs.
- Subject has received a non-biologic DMARD listed below or other drugs used in the treatment of RA within 28 days prior to baseline. Leflunomide is prohibited within 90 days prior to baseline. Alternatively, leflunomide is prohibited at least 28 days prior to baseline if washout with cholestyramine for at least 17 days is completed within 28 days prior to baseline. However, topical drugs other than those for the treatment of RA may be used concomitantly.
- Subject has received Chinese herbal medicines listed below or other herbal drugs used in the treatment of RA within 28 days prior to baseline.
- Subject has received tofacitinib, baricitinib or other JAK inhibitor (including other investigational drugs).
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 |
|---|---|---|
| PeficitinibAlso: ASP015KOral | Drug | ASP015K 100 mg, ASP015K 150 mg, Placebo/ASP015K |
| PlaeboOral | Drug | Placebo/ASP015K |
| Disease-modifying antirheumatic drugs (DMARDs)As necessary concomitant medications, DMARDs listed below will be administered orally unless specified. For subjects who are inadequate responders to methotrexate (MTX): MTX. For subjects who are intolerant of MTX: either of DMARDs listed; hydroxychloroquine, salazosulfapyridine, gold (injection or oral), D-penicillamine, lobenzarit, actarit, bucillamine and iguratimod. | Drug | ASP015K 100 mg, ASP015K 150 mg, Placebo/ASP015K |
Primary outcome
American College of Rheumatology (ACR)20 response rate at Week 24
Time frame: At Week 24
The ACR20 response requires that all criteria from (1) to (3) be met compared with Week 0 (baseline); (1), Tender Joint Count (TJC) >= 20% reduction; (2), Swollen Joint Count (SJC) >= 20% reduction;(3) >= 20% improvement in three or more of the following five parameters - [1] subject's assessment of pain, [2] Subject's Global Assessment of Arthritis (SGA), [3] Physician's Global Assessment of Arthritis (PGA), [4] health assessment questionnaire-disability index (HAQ-DI), [5] acute phase reactant (C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)).
33 secondary outcomes
ACR20 response rate
Time frame: Up to Week 52
ACR50 response rate
Time frame: Up to Week 52
ACR70 response rate
Time frame: Up to Week 52
Change from baseline in disease activity score (DAS) 28-C-reactive protein (CRP) scores
Time frame: From baseline (Week 0) to Week 52
Change from baseline in DAS28- erythrocyte sedimentation rate (ESR) scores
Time frame: From baseline (Week 0) to Week 52
Change from baseline in Tender Joint Count (TJC) (68 joints)
Time frame: From baseline (Week 0) to Week 52
Change from baseline in Swollen Joint Count (SJC) (66 joints)
Time frame: From baseline (Week 0) to Week 52
Percentage of participants achieving DAS28-CRP scores for remission
Time frame: Up to Week 52
Percentage of participants achieving DAS28-ESR scores for remission
Time frame: Up to Week 52
Percentage of participants achieving low disease activity by DAS28-CRP
Time frame: Up to Week 52
Percentage of participants achieving low disease activity by DAS28-ESR
Time frame: Up to Week 52
Change from baseline in CRP
Time frame: From baseline (Week 0) to Week 52
Change from baseline in ESR
Time frame: From baseline (Week 0) to Week 52
Percentage of participants with good European League Against Rheumatism (EULAR) response
Time frame: Up to Week 52
Percentage of participants with good or moderate EULAR response
Time frame: At Week 52
Percentage of participants achieving ACR/EULAR remission
Time frame: At Week 52
Percentage of participants achieving Simplified Disease Activity Index (SDAI) remission (SDAI score ≤ 3.3)
Time frame: Up to Week 52
Change from baseline in SDAI score
Time frame: From baseline (Week 0) to Week 52
Change from baseline in Physician's Global Assessment of Arthritis (PGA) (VAS)
Time frame: From baseline (Week 0) to Week 52
Change from baseline in SGA (VAS)
Time frame: From baseline (Week 0) to Week 52
Change from baseline in participant's assessment of pain (VAS)
Time frame: From baseline (Week 0) to Week 52
Incidence of participant withdrawal due to the lack of efficacy
Time frame: Up to Week 56
Change from baseline in health assessment questionnaire-disability index (HAQ-DI) score
Time frame: From baseline (Week 0) to Week 52
Change from baseline in Short Form Health Survey - 36 questions, version 2 (SF-36v2)® score
Time frame: From baseline (Week 0) to Week 52
Change from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) score
Time frame: From baseline (Week 0) to Week 52
Pharmacokinetics (PK) of ASP015K in plasma: post-dose concentration
Time frame: 2 hours post-dose at either Week 4 or Week 8
PK of ASP015K in plasma: trough concentration (Ctrough)
Time frame: Up to Week 52
Safety assessed by incidence of adverse events (AEs)
Time frame: Up to Week 56
Number of participants with vital sign abnormalities and/or AEs
Time frame: Up to Week 56
Number of participants with body weight abnormalities and/or AEs
Time frame: Up to Week 56
Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs
Time frame: Up to Week 52
Number of participants with central ECG abnormalities and/or AEs
Time frame: Up to Week 8
Number of participants with chest radiography abnormalities and/or AEs
Time frame: Up to Week 52
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2024.
- Derived from this study: PubMed 38357391Yang Y, Li J, Liu J, Liu L, Wang Y, Hu J, Li Z, Gu J, Zhang X, Xiao Z, Zheng J, Liu L, Li Z, Wei JC. Safety and efficacy of peficitinib in Asian patients with rheumatoid arthritis who had an inadequate response or intolerance to methotrexate: results of a multicenter, randomized, double-blind, placebo-controlled phase 3 study. Lancet Reg Health West Pac. 2023 Oct 18;42:100925. doi: 10.1016/j.lanwpc.2023.100925. eCollection 2024 Jan.
- Link to results on the Astellas Clinical Study Results websiteLink provided by the sponsor.
- Link to plain language summary of the study on the Trial Results Summaries websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
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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.
Medical Monitor study director
Astellas Pharma Inc
43 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Peficitinib, Plaebo and Disease-modifying antirheumatic drugs (DMARDs) in people with Rheumatoid Arthritis (RA), run by Astellas Pharma China, Inc. at 43 sites in 3 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 19 inclusion and 60 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 21 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in China, South Korea, Taiwan. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
American College of Rheumatology (ACR)20 response rate at Week 24 (time frame: At Week 24). 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 NCT03660059, 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 21 Oct 2024.