Arthritis, RheumatoidPhase 4NCT02837978

The Efficacy and Safety of Tacrolimus in Refractory Rheumatoid Arthritis Patients for 6 Months and Long-term Treatment

A Phase 4 study testing Tacrolimus and MTX in people with Arthritis, Rheumatoid, run by Qiang Shu at 1 site in China.

Completed

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

Trial summary

This study is designed to observed prospectively the efficacy and safety of 6 months and long-term treatment of Tacrolimus alone or with methotrexate (MTX) in moderate and severe Chinese RA patients who shown insufficiency response or intolerance to DMARDs Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Arthritis, Rheumatoid
What is being tested?: Tacrolimus and MTX
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 150 participants
Where: 1 siteChina
Study dates: Jan 2015to 30 Dec 2022
Phase: Phase 4
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 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients diagnosed based on 1987 ACR classification criteria for rheumatoid arthritis;
Age ≥18 years;
Patients have a history of DMARDs including csDMARDs（methotrexate，leflunomide, hydroxychloroquine, iguratimod, sulfasalazine) or any biologic DMARDs（TNFi，tocilizumab or Tofacitinib），prednisone or Chinese traditional Medicine（tripterygium Glycosides，Sinomenine）for 3 months, but couldn't achieve clinical remission， or couldn't tolerate one or more DMARDs;
Medium or high disease activity (DAS28≥3.2);
Extra-articular manifestations (such as pulmonary fibrosis, proteinuria, leukopenia and peripheral neuropathy ) of RA patients are stable or no significant progress;
Dose of prednisone and NSAIDs remain stable for at least one month.

Who cannot join

Patients with acute or chronic infections such as active bacterial, viral, fungal, tuberculosis infection or active hepatitis B;
Platelet counts(PLT) <80 x 10^9 / L, or white blood cell (WBC) <3 x 10^9 / L;
Propionate acid aminotransferase (ALT) or aspartate aminotransferase (AST) is two times higher than the upper limit of normal;
Renal insufficiency: serum Cr ≥ 176 umol / L;
Pregnant or nursing women (breastfeeding) ；
Patients has a history of malignancy (cure time in less than 5 years);
Patients with severe or poorly controlled hypertension, diabetes or cardiac dysfunction;
Other comorbidities that cannot be treated with immune suppressants. In addition, once patients experience severe adverse drug reactions、ineffective treatment or rapid progression of rheumatoid arthritis, then quit this research.

Trial locations and contacts

1 site in 1 country.

China1 site

Qilu Hospital
Jinan, Shandong, 250012

Other trials in China

About this study

Official title: Prospective Clinical Study to Observe the Efficacy and Safety of Tacrolimus in Refractory Rheumatoid Arthritis Patients for 6 Months Treatment in China

Read the detailed description

This study will enroll 150 cases of refractory rheumatoid arthritis (RA) patients in Chinese，who are in moderate or severe disease activity and insufficiency response or intolerance to DMARDs. The participants plan to be treated with Tacrolimus alone, or along with methotrexate (MTX) if participants were tolerant to MTX. The efficacy and safety of 6 month Tacrolimus treatment in RA patients will be evaluated with DAS28 and other disease activity indices.

Conditions: Arthritis, Rheumatoid
Being tested: Tacrolimus, MTX
Keywords: Arthritis, Rheumatoid, Tacrolimus, Treatment outcome, 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.

TacrolimusDrug
Also called FK506
Tacrolimus capsule: 0.5mg to 1mg, po, twice per day (Bid)，adjusted by its concentration in blood or due to patient response. Then may titer down until the endpoint.
MTXDrug
Also called methotrexate
MTX：5mg to 15mg, po, once per week (Qw) until the endpoint or adjusted due to unacceptable toxicity develops.

Study groups in NCT02837978
Study group	Role	What they receive
Tacrolimus group	Experimental	RA patients treated with tacrolimus, without MTX Receives: Drug: Tacrolimus
Tacrolimus + MTX group	Active comparator	RA patients treated with tacrolimus and MTX Receives: Drug: Tacrolimus; Drug: MTX

What is being measured

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

Change from baseline Disease Activity Score 28 (DAS28-ESR) at 24 and longer weeks.
Change from baseline Disease Activity Score 28 (DAS28) erythrocyte sedimentation rate (ESR) at 24 and longer weeks.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week

Secondary outcomes (14)

Change from baseline ACR20 response rate at 24 and longer weeks.
Change from baseline ACR20 response rate at 24 and longer weeks.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
The clinical remission rate at 24 and longer weeks.
The percentage of patients who achieve clinical remission patients at the endpoint or withdraw timepoint.
High disease activity: DAS28 score exceeding 5.1, Moderate disease activity: DAS28 score of exceeding 3.2 to 5.1, Low disease activity (LDA): DAS28 score of less than or equal to 3.2, Remission: DAS28 score is less than 2.6. clinical remission means Low disease activity or remission.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Clinical response was analyzed using the European League Against Rheumatism (EULAR) improvement criteria.
Good response: ΔDAS28 > 1.2 and DAS28 ≤3.2； Moderate response: 1.2 ≥ΔDAS28 > 0.6 and 3.2<DAS28 ≤5.1； or ΔDAS28 > 1.2 and still DAS28>3.2； No response:ΔDAS28≤0.6； or 1.2≥ΔDAS28 > 0.6 and DAS28>5.1。
Measured: 12 week,3 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline Simplified Disease Activity Index (SDAI) at 24 and longer weeks.
Change from baseline Simplified Disease Activity Index (SDAI) at 24 and longer weeks.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline Clinical disease activity index (CDAI) at 24 and longer weeks.
Change from baseline Clinical disease activity index (CDAI) at 24 and longer weeks.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline Erythrocyte Sedimentation Rate (ESR) at 24 and longer weeks.
Change from baseline Erythrocyte Sedimentation Rate (ESR) at 24 and longer weeks.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline C-Reactive Protein (CRP) at 24 and longer weeks.
Change from baseline C-Reactive Protein (CRP) at 24 and longer weeks.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline swollen joint number (SW28) at 24 and longer weeks.
Change from baseline swollen joint number (SW28) at 24 and longer weeks. SW28 means the number of joints with swelling counted in 28 synovial joints, including proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2) and knees (2) bilateral.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline tenderness joint number (T28) at 24 and longer weeks.
Change from baseline tenderness joint number (T28) at 24 and longer weeks. T28 means the number of joints with tenderness upon touching counted in 28 synovial joints, including proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2) and knees (2) bilateral.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline patient global assessment(PGA) at 24 and longer weeks.
Change from baseline patient global assessment(PGA) at 24 and longer weeks.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline physician global assessment(PHGA) at 24 and longer weeks.
Change from baseline physician global assessment(PHGA) at 24 and longer weeks.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline Health Assessment Questionnaire (HAQ) at 24 and longer weeks.
Change from baseline Health Assessment Questionnaire (HAQ) at 24 and longer weeks.
Measured: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Safety assessed by Adverse Events (AEs)
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product
Measured: Up to 144 weeks
Safety assessed by incidence of serious adverse events (SAE)
Adverse Event is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event.
Measured: Up to 144 weeks

Timeline

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

Jan 201530 Dec 2022

First posted20 Jul 2016 (estimated)
Study startJan 2015
Primary completion30 Sep 2022
Study completion30 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Arthritis, RheumatoidStudies 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 4
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 150 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02837978
Sponsor's protocol ID: Tacrolimus RA QiluH
Status last verified: Nov 2023
First submitted: 13 Jul 2016
Last updated: 18 Nov 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: De-identified individual participant data for all primary and secondary outcome measures will be made available within 12 months of study completion.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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R-2487 in Patients With Sjogren's Syndrome (SjD)
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RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
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Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis

All Arthritis, Rheumatoid trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Prospective Clinical Study to Observe the Efficacy and Safety of Tacrolimus in Refractory Rheumatoid Arthritis Patients for 6 Months Treatment in China
ClinicalTrials.gov ID: NCT02837978
Acronym / sponsor ID: Tacrolimus RA QiluH
Conditions: Arthritis, Rheumatoid
Keywords: Arthritis, Rheumatoid, Tacrolimus, Treatment outcome, Safety
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 150 participants (actual)
Lead sponsor: Qiang ShuUniversity, hospital or other
Study start: Jan 2015 (actual)
Primary completion: 30 Sep 2022 (actual)
Study completion: 30 Dec 2022 (actual)
First posted: 20 Jul 2016 (estimated)
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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Tacrolimus group	Experimental	Drug: TacrolimusRA patients treated with tacrolimus, without MTX
Tacrolimus + MTX group	Active comparator	Drug: Tacrolimus, Drug: MTXRA patients treated with tacrolimus and MTX

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Patients diagnosed based on 1987 ACR classification criteria for rheumatoid arthritis;
Age ≥18 years;
Patients have a history of DMARDs including csDMARDs（methotrexate，leflunomide, hydroxychloroquine, iguratimod, sulfasalazine) or any biologic DMARDs（TNFi，tocilizumab or Tofacitinib），prednisone or Chinese traditional Medicine（tripterygium Glycosides，Sinomenine）for 3 months, but couldn't achieve clinical remission， or couldn't tolerate one or more DMARDs;
Medium or high disease activity (DAS28≥3.2);
Extra-articular manifestations (such as pulmonary fibrosis, proteinuria, leukopenia and peripheral neuropathy ) of RA patients are stable or no significant progress;

Key exclusion criteria (8 listed)

Patients with acute or chronic infections such as active bacterial, viral, fungal, tuberculosis infection or active hepatitis B;
Platelet counts(PLT) <80 x 10^9 / L, or white blood cell (WBC) <3 x 10^9 / L;
Propionate acid aminotransferase (ALT) or aspartate aminotransferase (AST) is two times higher than the upper limit of normal;
Renal insufficiency: serum Cr ≥ 176 umol / L;
Pregnant or nursing women (breastfeeding) ；

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
TacrolimusAlso: FK506Tacrolimus capsule: 0.5mg to 1mg, po, twice per day (Bid)，adjusted by its concentration in blood or due to patient response. Then may titer down until the endpoint.	Drug	Tacrolimus + MTX group, Tacrolimus group
MTXAlso: methotrexateMTX：5mg to 15mg, po, once per week (Qw) until the endpoint or adjusted due to unacceptable toxicity develops.	Drug	Tacrolimus + MTX group

Primary outcome

Change from baseline Disease Activity Score 28 (DAS28-ESR) at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline Disease Activity Score 28 (DAS28) erythrocyte sedimentation rate (ESR) at 24 and longer weeks.

14 secondary outcomes

Change from baseline ACR20 response rate at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
The clinical remission rate at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Clinical response was analyzed using the European League Against Rheumatism (EULAR) improvement criteria.
Time frame: 12 week,3 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline Simplified Disease Activity Index (SDAI) at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline Clinical disease activity index (CDAI) at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline Erythrocyte Sedimentation Rate (ESR) at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline C-Reactive Protein (CRP) at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline swollen joint number (SW28) at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline tenderness joint number (T28) at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline patient global assessment(PGA) at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline physician global assessment(PHGA) at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Change from baseline Health Assessment Questionnaire (HAQ) at 24 and longer weeks.
Time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week
Safety assessed by Adverse Events (AEs)
Time frame: Up to 144 weeks
Safety assessed by incidence of serious adverse events (SAE)
Time frame: Up to 144 weeks

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 18 Nov 2023.
Individual participant dataSharing planned: No. De-identified individual participant data for all primary and secondary outcome measures will be made available within 12 months of study completion.

Related trials for Arthritis, Rheumatoid

RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
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RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis

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.

Qiang Shu, Dr. principal investigator

Qilu Hospital of Shandong University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tacrolimus and MTX in people with Arthritis, Rheumatoid, run by Qiang Shu at 1 site in China.

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 6 inclusion and 8 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 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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?

Change from baseline Disease Activity Score 28 (DAS28-ESR) at 24 and longer weeks. (time frame: 12 week, 24week,36 week,48 week,72 week,96 week,120 week,144 week). 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 NCT02837978.

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 18 Nov 2023.