UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000023989
Receipt number R000024831
Scientific Title Efficacy and safety of hydroxychloroquine for Japanese patients with rheumatoid arthritis
Date of disclosure of the study information 2017/01/01
Last modified on 2023/09/02 05:16:11

* This page includes information on clinical trials registered in UMIN clinical trial registed system.
* We don't aim to advertise certain products or treatments


Basic information

Public title

Efficacy and safety of hydroxychloroquine for Japanese patients with rheumatoid arthritis

Acronym

Efficacy and safety of hydroxychloroquine for Japanese patients with rheumatoid arthritis

Scientific Title

Efficacy and safety of hydroxychloroquine for Japanese patients with rheumatoid arthritis

Scientific Title:Acronym

Efficacy and safety of hydroxychloroquine for Japanese patients with rheumatoid arthritis

Region

Japan


Condition

Condition

rheumatoid arthritis

Classification by specialty

Clinical immunology

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To evaluate the efficacy and safety in Japanese patients with rheumatoid arthritis

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase II,III


Assessment

Primary outcomes

Achievement rate of ACR20 at week 24

Key secondary outcomes

Achievement rate of improving DAS28 category at weeks 4, 8, 12 and 24
Achievement rate of low disease activity in DAS 28 at weeks 4, 8, 12 and 24
Achievement rate of clinical remission in DAS 28 at weeks 4, 8, 12 and 24
Achievement rate of functional remission in HAQ at weeks 4, 8, 12 and 24
Achievement rate of structural remission in modified total Sharp score at week 24
Achievement rate of ACR 20 at at weeks 4, 8, and 12
Achievement rate of ACR 50/70 at weeks 4, 8, 12 and 24
Adverse effects during whole study


Base

Study type

Interventional


Study design

Basic design

Single arm

Randomization

Non-randomized

Randomization unit


Blinding

Open -no one is blinded

Control

Historical

Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Treatment with hydroxyxhloroquine for 24 weeks.

Interventions/Control_2


Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


Interventions/Control_6


Interventions/Control_7


Interventions/Control_8


Interventions/Control_9


Interventions/Control_10



Eligibility

Age-lower limit

18 years-old <=

Age-upper limit


Not applicable

Gender

Male and Female

Key inclusion criteria

Patients who fulfill the following four criteria in Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine
1) Age 18- years
2) RA satisfying either the 1987 ACR criteria or 2010 ACR/ EULAR criteria
3) active disease (DAS28 2.6-) with poor prognostic factors with methotrexate treatment for over 3 months (stable dose for at least 4 weeks) or active disease with two or more oral conventional synthetic DMARDs for over 3 months (stable dose for at least 4 weeks)
4) One or more swollen joints and one or more tender joints
5) Written informed consent provided
6) Prior use of biological agent is permitted

Key exclusion criteria

1) Pregnancy or hope to bear a child
2) Contraindication to HCQ, e.g. history of retinopathy and hypersensitivity to 4-aminoquinoline
3) Uncontrollable diabetes mellitus
4) Porphyria
5) Psoriasis
6) G6PD deficiency
7) Ineligible for the study judged by physicians

Target sample size

60


Research contact person

Name of lead principal investigator

1st name Tsutomu
Middle name
Last name Takeuchi

Organization

Keio University School of Medicine

Division name

Division of Rheumatology

Zip code

160-8582

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, Japan

TEL

03-5363-3786

Email

tsutake@z5.keio.jp


Public contact

Name of contact person

1st name Yuko
Middle name
Last name Kaneko

Organization

Keio University School of Medicine

Division name

Division of Rheumatology

Zip code

160-8582

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, Japan

TEL

03-5363-3786

Homepage URL


Email

ykaneko@z6.keio.jp


Sponsor or person

Institute

Division of Rheumatology, Keio University School of Medicine

Institute

Department

Personal name



Funding Source

Organization

Sanofi

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization



Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

Certified Clinical Research Review Board, Keio University

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, Japan

Tel

03-3353-1211

Email

med-nintei-jimu@adst.keio.ac.jp


Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions

慶應義塾大学病院(東京都)


Other administrative information

Date of disclosure of the study information

2017 Year 01 Month 01 Day


Related information

URL releasing protocol

https://jrct.niph.go.jp/latest-detail/jRCTs031180050

Publication of results

Published


Result

URL related to results and publications

https://academic.oup.com/mr/advance-article-abstract/doi/10.1093/mr/roac153/6885349?redirectedFrom=f

Number of participants that the trial has enrolled

60

Results

The addition of HCQ to csDMARDs was effective, with no new safety signal in patients with RA.

Results date posted

2023 Year 09 Month 02 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

Variables HCQ (n = 60)
Female 55 (91.7)
Age 63.7 (13.0)
Seropositive for RF or anti CCP 51 (85.0)
Disease duration, years 12.4 (10.4)
History of biological agent use 11 (18.3)
Methotrexate use 51 (85.0)
csDMARDs other than methotrexate 9 (15.0)
Concomitant glucocorticoid use 9 (15.0)
C reactive protein, mg per dL 0.7 (1.5)
Erythrocyte sedimentation rate, mm per hr 31.4 (26.4)
DAS28-ESR 4.4 (0.9)
DAS28-CRP 3.6 (0.8)
SDAI 17.9 (7.8)
CDAI 17.2 (7.4)
HAQ DI 0.7 (0.7)
DAS28-ESR low disease activity3 (5.0)
Swollen joint count 0-28 5.4 (3.3)
Tender joint count 0-28 4.6 (2.9)
Swollen joint count 0-66 7.0 (4.4)
Tender joint count 0-68 5.8 (4.0)
HAQ-DI remission 32 (53.3)
Patient global assessment, mm 32.4 (23.2)
Evaluator global assessment, mm 40.0 (22.8)
Pain visual analog scale, mm 32.3 (23.8)
HCQ dose
200 mg per day 24 (60.0)
200 mg and 400 mg on alternate days 34 (56.7)
400 mg per day 2 (3.3)

Participant flow

Sixty patients were enrolled and received HCQ. Seven patients withdrew during the 24-week period due to AEs (N = 6; skin rash in two patients, arthritis exacerbation in two patients, diarrhea in one patient, and tremor in one patient) and limited transportation to the hospital because of the Covid-19 pandemic (N = 1). Therefore, 53 patients completed HCQ therapy for 24 weeks and were considered candidates for propensity score matching.
As described in the Methods section, we identified 276 patients in our registry as candidates for propensity score matching for establishing a historical control group. By using propensity score matching, 46 patients in each group were selected for further analysis.

Adverse events

Fifty nine cases of Adverse events occurred in 36 patients . The most frequent adverse events were infections and infestations, which occurred in 15 patients, followed by gastrointestinal disorders in 11 patients. Although there were three events of bacterial pneumonia and one event of herpes zoster, they were treated without hospitalization and did not require HCQ cessation. Besides diarrhea, epigastralgia, stomatitis, loss of appetite, xerostomia and gingivitis were observed as non serious adverse events, all of which were cured with supportive treatment without reducing the dose of HCQ. Serious adverse events occurred in two patients (cataract operation with one-night hospitalization, and cerebral hemorrhage) during the 8 week post observation period. Six patients withdrew from the study before week 24 due to adverse events (one diarrhea, one tremor, two arthritis exacerbation, two drug-related eruptions). This Diarrhea and two drug-related eruptions which led to withdrawal occurred early after HCQ initiation (within 4 weeks). No HCQ retinopathy was observed during the study.

Outcome measures

Primary endpoint
 Rate of achieving ACR20

Secondary endpoint
 Achievement rate of improving more than one DAS28 category at week 4, week 8 and week 12
 Achievement rate of low disease activity with DAS 28 at week 4, week8, week 12 and week 24
 Achievement rate of clinical remission with DAS 28 at week 4, week8, week 12 and week 24
 Achievement rate of functional remission with HAQ (HAQ less than 0.5) at week 4, week8, week 12 and week 24
 Achievement rate of structural remission with modified total Sharp (TSS less than 0.5) score at week 4, week8, week 12 and week 24
 Achievement rate of ACR20, 50, 70 at week 4, week8, week 12 and week 24
 Rate of adverse effects during whole study

Exploratory endpoint
 Serum cytokine levels at week 4, week8, week 12 and week 24
 Peripheral blood cell surface markers at week 4, week8, week 12 and week 24

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2016 Year 08 Month 26 Day

Date of IRB

2015 Year 04 Month 14 Day

Anticipated trial start date

2016 Year 11 Month 01 Day

Last follow-up date

2019 Year 06 Month 30 Day

Date of closure to data entry

2019 Year 09 Month 30 Day

Date trial data considered complete

2019 Year 10 Month 30 Day

Date analysis concluded

2020 Year 04 Month 01 Day


Other

Other related information



Management information

Registered date

2016 Year 09 Month 09 Day

Last modified on

2023 Year 09 Month 02 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024831


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name