Clinical trial NCT02884635: A Study to Evaluate the Efficacy and Safety of ASP1707 in Postmenopausal Female Patients With Rheumatoid Arthritis Taking Methotrexate
Official title: Phase IIa Study of ASP1707 A Randomized, Placebo-Controlled, Double-Blind, Parallel Group Phase 2a Study of ASP1707 in Postmenopausal Female Patients With Rheumatoid Arthritis (RA) Taking Methotrexate (MTX)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Methotrexate
ASP1707
Rheumatoid arthritis
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2016-08-31
Enrollment: 72
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the efficacy, pharmacokinetics, pharmacodynamics and safety of ASP1707 in combination with MTX in postmenopausal female patients with RA.


Eligibility criteria: Inclusion Criteria:

* Subject has RA that was diagnosed according to the 1987 ACR criteria or the 2010 ACR/EULAR criteria.
* Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class I, II or, III.
* subject has active RA as evidenced by both of the followings:

  * ≥ 6 tender/painful joints (using 68-joint assessment)
  * ≥ 6 swollen joints (using 66-joint assessment)
* CRP (C-reactive protein) of \> 0.3 mg/dL or ESR (Erythrocyte sedimentation rate) of \> 28 mm/hr at screening.
* Subject who continuously received MTX and who is able to continue stable dose of MTX.
* Subject who did not receive the following drugs, or received the drugs with stable dosage:

Non-steroidal anti-inflammatory drugs, oral morphine or equivalent opioid analgesics, acetaminophen, or oral corticosteroids.

Exclusion Criteria:

* Inadequate responders to a biologic DMARD (Disease-modifying antirheumatic drug).
* Subject has taken other investigational research products are prohibited within 12 weeks (84 days) or within 5 half-lives, whichever is longer, prior to screening.
* Subject has undergone surgery which has residual effects on the assessed joints, or is scheduled to undergo surgery that may affect the study evaluation of the assessed joints.
* Subject has another type of inflammatory arthritis other than RA.
* Subject who meets any of the following criteria of laboratory values at screening:

  * White blood cell count \<4000/μL
  * Platelet count \<100000/μL
  * ALT (Alanine Aminotransferase) ≥ 2 x ULN (Upper Limit of Normal)
  * AST (Aspartate Aminotransferase) ≥ 2 x ULN
  * Total bilirubin ≥ 1.5 x ULN
  * Positive Hepatitis B surface antigen, Hepatitis B virus-DNA quantitation, or Hepatitis C virus antibody
* Subject has a positive QuantiFERON-TB Gold test or T-spot.
* Subject has a history of or concurrent malignant tumor.
* Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, infectious, or autoimmune disease except for RA, or diseases which preclude the subject's participation in the study.
* Subject has a history of clinically significant allergy.
* Subject has clinically significant abnormalities on the 12-lead Electrocardiogram.
* Subject has a history of positive Human Immunodeficiency Virus infection.

Primary outcomes:
measure: ACR20 response rate
timeFrame: Week 12
Secondary outcomes:
measure: ACR20 response rate
timeFrame: Up to Week 8
measure: ACR50 response rate
timeFrame: Up to Week 12
measure: ACR70 response rate
timeFrame: Up to Week 12
measure: Change from baseline in DAS28-CRP score
timeFrame: Baseline and Up to Week 12
measure: Change from baseline in DAS28-ESR score
timeFrame: Baseline and Up to Week 12
measure: Change from baseline in Tender Joint Count (68 joints)
timeFrame: Baseline and Up to Week 12
measure: Change from baseline in Swollen Joint Count (66 joints)
timeFrame: Baseline and Up to Week 12
measure: Percentage of subjects achieving DAS28-CRP score and DAS28-ESR score for remission (<2.6)
timeFrame: Up to Week 12
measure: Percentage of subjects achieving DAS28-CRP score and DAS28-ESR score for low disease activity (≤3.2)
timeFrame: Up to Week 12
measure: Change from baseline in CRP
timeFrame: Baseline and Up to Week 12
measure: Change from baseline in ESR
timeFrame: Baseline and Up to Week 12
measure: Percentage of subjects achieving EULAR response criterion of "Good Response"
timeFrame: Up to Week 12
measure: Percentage of subjects achieving EULAR response criterion of "Good Response" or "Moderate Response"
timeFrame: Up to Week 12
measure: Percentage of subjects achieving ACR/EULAR score for remission
timeFrame: Up to Week 12
measure: Percentage of subjects achieving SDAI score ≦ 3.3 (SDAI remission)
timeFrame: Up to Week 12
measure: Change from baseline in the SDAI score
timeFrame: Baseline and Up to Week 12
measure: Change from baseline for the HAQ-DI
timeFrame: Baseline and Up to Week 12
measure: Safety assessed by incidence of adverse events
timeFrame: Up to Week 13
measure: Safety assessed by body temperature
timeFrame: Up to Week 13
measure: Safety assessed by pulse rate
timeFrame: Up to Week 13
measure: Safety assessed by blood pressure in sitting position
timeFrame: Up to Week 13
measure: Safety assessed by laboratory tests: Hematology
timeFrame: Up to Week 13
measure: Safety assessed by laboratory tests: Biochemistry
timeFrame: Up to Week 13
measure: Safety assessed by laboratory tests: Urinalysis
timeFrame: Up to Week 13
measure: Safety assessed by standard 12-lead electrocardiogram
timeFrame: Up to Week 13
measure: Safety assessed by weight
timeFrame: Up to Week 13
measure: Plasma concentration of ASP1707
timeFrame: Up to Week 12
measure: Plasma concentration of metabolite of ASP1707
timeFrame: Up to Week 12
measure: Pharmacodynamics assessed by endocrinology tests
timeFrame: Up to Week 13
measure: Pharmacodynamics assessed by plasma concentration of TNF-α
timeFrame: Up to Week 13
measure: Pharmacodynamics assessed by plasma concentration of MMP3
timeFrame: Up to Week 13
measure: Pharmacodynamics assessed by plasma concentration of IL-6
timeFrame: Up to Week 13
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Site JP00022
city: Aichi
country: Japan
facility: Site JP00023
city: Chiba
country: Japan
facility: Site JP00017
city: Ehime
country: Japan
facility: Site JP00026
city: Fukui
country: Japan
facility: Site JP00025
city: Fukuoka
country: Japan
facility: Site JP00012
city: Fukuoka
country: Japan
facility: Site JP00018
city: Fukuoka
country: Japan
facility: Site JP00019
city: Gunma
country: Japan
facility: Site JP00006
city: Gunma
country: Japan
facility: Site JP00024
city: Hiroshima
country: Japan
facility: Site JP00010
city: Hiroshima
country: Japan
facility: Site JP00011
city: Hokkaido
country: Japan
facility: Site JP00001
city: Hokkaido
country: Japan
facility: Site JP00002
city: Hokkaido
country: Japan
facility: Site JP00003
city: Iwate
country: Japan
facility: Site JP00004
city: Iwate
country: Japan
facility: Site JP00005
city: Kagoshima
country: Japan
facility: Site JP00016
city: Kanagawa
country: Japan
facility: Site JP00007
city: Kanagawa
country: Japan
facility: Site JP00021
city: Kumamoto
country: Japan
facility: Site JP00014
city: Kumamoto
country: Japan
facility: Site JP00015
city: Nagasaki
country: Japan
facility: Site JP00013
city: Oita
country: Japan
facility: Site JP00020
city: Shizuoka
country: Japan
facility: Site JP00008
city: Shizuoka
country: Japan
facility: Site JP00009
city: Tokyo
country: Japan
facility: Site JP00027
Study officials:
affiliation: Astellas Pharma Inc
name: Medical Director
role: STUDY_DIRECTOR
References: