A Study to Investigate the Safety, Tolerability, and Efficacy of TAK-079 in Participants With Generalized Myasthenia Gravis
- Conditions
- Generalized Myasthenia GravisMedDRA version: 21.1Level: PTClassification code 10028417Term: Myasthenia gravisSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-003383-47-IT
- Lead Sponsor
- MILLENNIUM PHARMACEUTICALS, INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 36
Each patient must meet all the following inclusion criteria to be randomized to treatment:
1. The patient understands and agrees to study participation by providing a signed and dated written informed consent form (ICF) and any required privacy authorization before the initiation of any study procedures (as applicable, the patient’s legally acceptable representative may provide written informed consent in accordance with local and regional regulatory requirements) and, in the opinion of the investigator, is capable of complying with protocol requirements.
2. Aged 18 years or older.
3. Diagnosis of MG supported by a positive serologic test for anti-AChR or anti-MuSK antibodies at screening.
4. MGFA clinical classification class II to IV at screening.
5. MG-ADL total score of 6 or greater at screening, with at least 4 points of this score attributed to nonocular items.
6. If receiving immunosuppressive drugs (ie, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, cyclophosphamide), therapy must be ongoing for at least 6 months, with a stable dosing ongoing for at least 3 months before screening. Patients receiving azathioprine must be on a stable dose for at least 6 months before screening.
7. If receiving oral corticosteroids, therapy must be ongoing for at least 3 months, with a stable dose at least 1 month before screening. Corticosteroids, including dexamethasone, must be given as oral, daily or every-other-day therapy, as opposed to pulse therapy.
8. If receiving cholinesterase inhibitors, therapy with a stable dose is required at least 2 weeks before screening.
9. The doses of concomitant standard background therapy must be expected to remain stable throughout the study unless dose reduction is required due to toxicities. Allowed background therapy is defined as no more than a cholinesterase inhibitor ± corticosteroid ± one steroid-sparing immunosuppressive drug (limited to azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, or cyclophosphamide). Patients must be on at least one allowed background medication.
10. Female patients of childbearing potential are required to have a negative pregnancy test. Both male and female patients must practice an effective, reliable and approved contraceptive regimen during the study and for up to 90 days or 5 half-lives, whichever is longer, after discontinuation of treatment.
11. Patients must be able and willing to comply with study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11
Patients meeting any of the following exclusion criteria are not to be randomized to treatment:
1. History of thymoma or other thymic neoplasms.
2. History of thymectomy within 12 months before screening.
3. MGFA class I or V.
4. Received IVIg, SCIg (subcutaneous immunoglobulin), or plasmapheresis/plasma exchange within 4 weeks before screening.
5. Chronic obstructive pulmonary disease (COPD) or asthma with a pre-bronchodilatory forced expiratory volume in 1 second (FEV1) <50% of predicted normal.
Note: FEV1 testing is required for patients suspected of having COPD or asthma.
6. Received rituximab, belimumab, eculizumab, or any monoclonal antibody for immunomodulation within 6 months before first dosing. Patients with prior exposure to rituximab must have CD19 counts within the normal range at screening.
Known autoimmune disease other than MG that would interfere with the course and conduct of the study.
8. Received a live vaccine within 4 weeks before screening or has any live vaccination planned during the study.
9. Any medical condition that, in the opinion of the investigator, might interfere with the patient’s participation in the study (such as significant cardiovascular, pulmonary, hematologic, gastrointestinal, endocrinologic, hepatic, renal, neurologic, malignancy, or infectious disease), poses added risk for the patient, or could confound the
assessment of the patient.
10. Pregnancy or lactation during the screening period or on Day 1 before first dose of study drug.
11. Participation in any other investigational drug study or exposure to other investigational agent within 4 weeks or 5 half-lives, whichever is longer, before Day 1.
12. An opportunistic infection =12 weeks before initial study dosing or is currently receiving treatment for a chronic opportunistic infection, such as tuberculosis (TB), pneumocystis pneumonia, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria. A mild, localized herpes simplex infection within 12 weeks of study dosing is allowed, as long as the lesion has resolved without systemic therapy before Day 1.
13. Inadequate organ and bone marrow function:
a) Alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal (ULN).
b) Total bilirubin >1.5 times ULN (Note: Patients with a confirmed and documented diagnosis of Gilbert
syndrome are not excluded based on this criterion).
c) Platelets <75,000/mm3.
d) Absolute neutrophil count <1500/mm3.
e) Hemoglobin <8 g/dL.
f) IgG less than 5 g/L (500 mg/dL).
g) Lymphocyte count <500/mm3.
14. A positive T-cell interferon-¿ release assay (TIGRA) (result through QuantiFERON-TB Gold test or T-Spot/Elispot) at the screening visit, noting the following:
a) A purified protein derivative (PPD) skin test may be used if TIGRA testing is not available.
b) Patients with an indeterminate TIGRA result must meet the following criteria:
i. Negative PPD skin test (defined as <5 mm induration).
ii. At low risk of acquiring TB (eg, avoids close contact with TB-positive individual[s]) and/or chest x-ray =6 months before the screening visit that is consistent with no evidence of latent or active TB.
15. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the
completion of treatment according to this protocol.
16. A positive test result for hepatitis B surface antigen, or hepatitis B core antibody, hepatitis C antibody, or HIV antibody/antigen, at screening. However,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and tolerability of TAK-079 in patients with generalized MG who are receiving stable background therapy for MG.;Secondary Objective: To assess the effects of TAK-079 on MG disease activity using clinical rating scales and autoantibody levels.<br>;Primary end point(s): Percentage of patients with TEAEs, including Grade 3 or higher events, SAEs, and AEs leading to TAK-079 discontinuation.;Timepoint(s) of evaluation of this end point: TEAEs that occur after administration of the first dose of TAK-079 and through the end of the SFU period will be tabulated.
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: Throughout the study. Please refer to protocol Appendix A Schedule of Events;Secondary end point(s): 1. Score change from baseline in the following:<br>a) MG Activities of Daily Living (MG-ADL) score.<br>b) Quantitative Myasthenia Gravis (QMG) score.<br>c) Myasthenia Gravis Composite (MGC) score.<br>d) Revised 15-item Myasthenia Gravis Quality of Life scale (MG -QoL15r).<br>2. Change from baseline in anti-AChR antibody or anti-MuSK antibody levels.<br>3. The percentage of patients meeting minimal clinically important difference criteria in the respective MG clinical impairment scales (MG-ADL, QMG, MGC, MG-QoL15r).