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

Myasthenia Gravis, Generalized Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04431895
• Other study ID #: KY2020-019
• Status: Recruiting
• Phase: Early Phase 1
• Start date: June 11, 2020
• Est. completion date: February 9, 2023

Study information

• Verified date: September 2022
• Source: Huashan Hospital
• Contact: Chongbo Zhao, MD
• Phone: 86-21-52889999
• Email: zhao_chongbo[@]fudan.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: February 9, 2023
• Est. primary completion date: February 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis
• Myasthenia Gravis, Generalized

Intervention

Drug:
• Tofacitinib 5 MG
tofacitinib 5 mg tablet administered twice a day for 6 months

Locations

Country	Name	City	State
China	Huashan Hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Huashan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change From Baseline in Serum Titers of anti-acetylcholine receptor antibodies at Month 6	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.	Baseline, Month 6
Other	Change From Baseline in Inflammatory Cytokines at Month 6	MG is an autoimmune disease manifested by impairment at the neuromuscular junction featured by weakness and fatigability. We compared the inflammatory cytokines (IL-1ß,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-a and GM-CSF) at Baseline and Month 6.	Baseline, Month 6
Primary	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.	Baseline, Month 6
Secondary	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.	Baseline, Month 6
Secondary	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.	Baseline, Month 6
Secondary	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.	Baseline, Month 6
Secondary	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.	Baseline, Month 6