Clinical trial NCT05067348: Efficacy and Safety of Tocilizumab in the Treatment of Generalized Myasthenia Gravis
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial of the Efficacy and Safety of Tocilizumab in the Treatment of Generalized Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myasthenia Gravis, Generalized
Keywords: Generalized Myasthenia Gravis
Tocilizumab
Lead sponsor: Tang-Du Hospital
Sponsor class: OTHER
First posted: 2021-10-05
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized, double-blind, placebo-controlled, parallel-group study with optional open-label extension.

Detailed description: This study is a randomized, double-blind, placebo-controlled study, to be conducted at 6 study sites. Approximately 64 subjects will be enrolled. Patients with MG who are positive for anti-AChR antibodies will be enrolled. Patients who do not have anti-AChR or anti-MuSK antibodies will not be enrolled. Patients with MGFA classification II, III, or IV disease, MG-ADL score ≥ 5, QMG score ≥ 11, and use of a corticosteroid and/or non-steroidal immunosuppressant will be included in the study.

All subjects who complete the randomized controlled period will have the option to enroll in a 1-year open-label period.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of MG with anti-AChRantibody.
2. MGFA Clinical Classification Class II, III, or IV.
3. MG-ADL score of 5 or greater at screening and at randomization with \> 50% of this score attributed to non-ocular items.
4. QMG score of 11 or greater.
5. Subjects must be on:

   1. Cholinesterase inhibitor, with no dose increase within 4 weeks prior to randomization;
   2. Corticosteroids, with no dose increase within 4 weeks prior to randomization; or/and c. non-steroidal IST (including azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine A), with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization.

Exclusion Criteria:

1. Participants had clinically relevant active infections (such as sepsis, pneumonia, or abscess) or severe infections (resulting in hospitalization or requiring antibiotic treatment) in the 4 weeks before randomization;
2. Those with a history of high-risk tuberculosis infection, acquired tuberculosis infection, and chronic hepatitis;
3. Human immunodeficiency virus (HIV) infection;
4. Thymomas that have received thymectomy or planned thymectomy during RCP within 6 months before randomization, or require chemotherapy and/or radiotherapy at any time;
5. Received rituximab treatment in the past 6 months before randomization;
6. Received tocilizumab or eculizumab treatment within 3 months before randomization;
7. Received IVIG or plasma exchange within 4 weeks before randomization;
8. Unresected thymoma.
9. History of other tumor diseases.

Primary outcomes:
measure: Change in Quantitative Myasthenia Gravis (QMG) scores.
timeFrame: 16 weeks
Secondary outcomes:
measure: Proportion of subjects with both (1) ≥ 3-point improvement in QMG and (2) lasts ≥4 weeks
timeFrame: 16 weeks
measure: Proportion of subjects with both (1) ≥ 2-point improvement in MG-ADL and (2) lasts ≥4 weeks
timeFrame: 16 weeks
measure: Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Profile score.
timeFrame: 16 weeks
measure: Change in Myasthenia Gravis Composite (MGC) score
timeFrame: 16 weeks
measure: Change in Myasthenia Gravis Quality of Life-15, revised (MGQOL-15r) score.
timeFrame: 16 weeks
measure: Change in Myasthenia Gravis Impairment Index (MGII) score.
timeFrame: 16 weeks
measure: Number of participants with treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and treatment-emergent serious adverse events (TESAEs) during the randomized controlled period and open-label period.
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Xi'an
country: China
facility: Tangdu Hospital, The Fourth Military Medical University
state: Shaanxi
city: Shanghai
country: China
facility: Huashan Hospital
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin medical university general hospital
state: Tianjin
Study officials:
affiliation: The Second Affiliated Hospital of Air Force Medical University
name: Ting Chang, MD,PHD
role: STUDY_DIRECTOR
References: