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Safety And Efficacy Of Tofacitinib In Patients With Refractory Myasthenia Gravis: A Pilot Study

Primary Purpose

Myasthenia Gravis, Generalized

Status

Recruiting

Phase

Early Phase 1

Locations

China

Study Type

Interventional

Intervention

Tofacitinib 5 MG

About this trial

This is an interventional treatment trial for Myasthenia Gravis, Generalized focused on measuring myasthenia gravis, tofacitinib

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

fluctuating muscle weakness and fatigability classified as the Myasthenia Gravis Foundation of America (MGFA) clinical classification Type IIa-IVa;
more than 10% amplitude decrement in low frequency repetitive nerve stimulation, and less than 10% amplitude increment in high frequency repetitive nerve stimulation;
understanding and assigning the informed consent form, and having a good compliance with treatment.

meet all of the criteria in above as well as at least one of the below:

refractory: insufficient response to full dose- and course- steroids treatment (0.75-1mg per kg per day for at least 3-6 months), failure to respond adequately to tacrolimus (no less than 3mg per day) for 3 months;
severe or intolerable adverse effects from conventional immunosuppressive therapy.

Exclusion Criteria:

positive for muscle-specific kinase (MuSK) antibodies;
a tumor history except for thymoma;
a history of Type B and Type C hepatitis;
a history of tuberculosis or T-SPOT.TB tset positivity;
hepatic, renal and cardial insufficiency (baseline: ALT/AST>50U/L;BNP>200pg/ml）;
severe allergy or infection, or chronic or recurrent infection;
pregnancy;
hyperlipidemia;
participating other clinical trials

Sites / Locations

Huashan HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

tofacitinib 5mg twice a day

Arm Description

Outcomes

Primary Outcome Measures

Change From Baseline in Quantitative Myasthenia Gravis (QMG) Scores at Month 6

A quantitative MG scoring system (QMG Score) is essential in the objective evaluation of therapy for MG.This scoring system is based on quantitative testing of sentinel muscle groups. Total QMG score range from 0 (extreme disease severity) to 39 (none), higher score indicated less disease severity.

Secondary Outcome Measures

Change From Baseline in Myasthenia Gravis-related Activities of Daily Living (MG-ADL) Scores at Month 6

The myasthenia gravis activities of daily living (MG-ADL) profile is an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities.Total MG-ADL score range from 0 (none) to 24 (extreme disease conditions), higher score indicated more disease severity.

Change From Baseline in Manual Muscle Testing (MMT) Scores at Month 6

The MMT score is the sum of strength or function values assigned by the examining physician to 30 muscle groups usually affected by MG. Total MMT score range from 0 (none) to 124 (extreme muscle weakness), higher score indicated more disease severity.

Change From Baseline in Myasthenia Gravis-Quality of Life Questionnaire-15 item (MG-QOL15) Scores at Month 6

The MG-QOL15 is helpful in informing the clinician about the patient's perception of the extent of and dissatisfaction with MG-related dysfunction. Total MG-QOL15 score range from 0 (none) to 60 (extreme disease severity), higher score indicated more disease severity.

Change From Baseline in Doses of Steroids at Month 6

Steroids is recommended as the first-line treatment for myasthenia gravis. Here we followed the combined doseage of steroids while administrating tofacitinib for enrolled participants.

Full Information

NCT ID

NCT04431895

First Posted

June 12, 2020

Last Updated

September 1, 2022

Sponsor

Huashan Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04431895

Brief Title

Safety And Efficacy Of Tofacitinib In Patients With Refractory Myasthenia Gravis: A Pilot Study

Official Title

A Prospective,Single-center,Single-Arm,Single-Blind Pilot Study To Investigate The Efficacy Of Tofacitinib In Patients With Refractory Myasthenia Gravis

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

June 11, 2020 (Actual)

Primary Completion Date

February 4, 2023 (Anticipated)

Study Completion Date

February 9, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Huashan Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a 6 month study that will evaluate the efficacy of 5mg tofacitinib tablet taken twice a day in patients with refractory myasthenia gravis. Twenty adult participants will receive a four month treatment of tofacitinib followed by elution for one month.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myasthenia Gravis, Generalized

Keywords

myasthenia gravis, tofacitinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

tofacitinib 5mg twice a day

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Tofacitinib 5 MG

Intervention Description

tofacitinib 5 mg tablet administered twice a day for 6 months

Primary Outcome Measure Information:

Title

Change From Baseline in Quantitative Myasthenia Gravis (QMG) Scores at Month 6

Description

Time Frame

Baseline, Month 6

Secondary Outcome Measure Information:

Title

Change From Baseline in Myasthenia Gravis-related Activities of Daily Living (MG-ADL) Scores at Month 6

Description

Time Frame

Baseline, Month 6

Title

Change From Baseline in Manual Muscle Testing (MMT) Scores at Month 6

Description

Time Frame

Baseline, Month 6

Title

Change From Baseline in Myasthenia Gravis-Quality of Life Questionnaire-15 item (MG-QOL15) Scores at Month 6

Description

Time Frame

Baseline, Month 6

Title

Change From Baseline in Doses of Steroids at Month 6

Description

Steroids is recommended as the first-line treatment for myasthenia gravis. Here we followed the combined doseage of steroids while administrating tofacitinib for enrolled participants.

Time Frame

Baseline, Month 6

Other Pre-specified Outcome Measures:

Title

Change From Baseline in Serum Titers of anti-acetylcholine receptor antibodies at Month 6

Description

Anti-acetylcholine receptor antibodies are the major pathological autoantibodies of MG. For anti-AChR antibodies-positive candidates, we followed the antibodies titers at Month 6.

Time Frame

Baseline, Month 6

Title

Change From Baseline in Inflammatory Cytokines at Month 6

Description

MG is an autoimmune disease manifested by impairment at the neuromuscular junction featured by weakness and fatigability. We compared the inflammatory cytokines (IL-1β,IL-2,IL-4,IL-5,IL-6,IL-9,IL-10,IL-12p70,IL-13,IL-17A,IL-18,IL-21,IL-22,IL-23,IL-27,IFN-gamma,TNF-α and GM-CSF) at Baseline and Month 6.

Time Frame

Baseline, Month 6

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: fluctuating muscle weakness and fatigability classified as the Myasthenia Gravis Foundation of America (MGFA) clinical classification Type IIa-IVa; more than 10% amplitude decrement in low frequency repetitive nerve stimulation, and less than 10% amplitude increment in high frequency repetitive nerve stimulation; understanding and assigning the informed consent form, and having a good compliance with treatment. meet all of the criteria in above as well as at least one of the below: refractory: insufficient response to full dose- and course- steroids treatment (0.75-1mg per kg per day for at least 3-6 months), failure to respond adequately to tacrolimus (no less than 3mg per day) for 3 months; severe or intolerable adverse effects from conventional immunosuppressive therapy. Exclusion Criteria: positive for muscle-specific kinase (MuSK) antibodies; a tumor history except for thymoma; a history of Type B and Type C hepatitis; a history of tuberculosis or T-SPOT.TB tset positivity; hepatic, renal and cardial insufficiency (baseline: ALT/AST>50U/L;BNP>200pg/ml）; severe allergy or infection, or chronic or recurrent infection; pregnancy; hyperlipidemia; participating other clinical trials

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Chongbo Zhao, MD

Phone

86-21-52889999

zhao_chongbo@fudan.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Chong Yan, MD

Phone

86-21-52889999

yanc_huashan@163.com

Facility Information:

Facility Name

Huashan Hospital

City

Shanghai

ZIP/Postal Code

200040

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Chongbo Zhao, MD

Phone

+86 21 52889999

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Individual participant data (IPD) are not available to other researchers.

Learn more about this trial

Safety And Efficacy Of Tofacitinib In Patients With Refractory Myasthenia Gravis: A Pilot Study

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