A Study of TAK-079 in People With Generalized Myasthenia Gravis
Condition: Myasthenia Gravis
MeSH terms: Myasthenia Gravis; Muscle Weakness
Intervention: TAK-079; TAK-079 Placebo
Intervention description: TAK-079 subcutaneous injection; TAK-079 placebo-matching subcutaneous injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      Myasthenia gravis is an autoimmune condition that causes muscle weakness. Autoimmune means
      the body makes antibodies that attack its own cells and tissues. These types of antibodies
      are also known as autoantibodies. People with generalized myasthenia gravis have a weakness
      in many muscles.

      TAK-079 is a medicine to help people with generalized myasthenia gravis.

      The main aim of this study is to check if people with generalized myasthenia gravis have side
      effects from 2 doses of TAK-079. Other aims are to learn if TAK-079 improves their clinical
      condition and lowers their autoantibody levels.

      At the first visit, the study doctor will check if each person can take part. For those who
      can take part, participants will continue with their standard medicines for this condition
      during the study. Each participant will have a check-up by the study doctor.

      Then, the participants will have 1 of 3 treatments:

        -  A low dose of TAK-079.

        -  A high dose of TAK-079.

        -  A placebo. In this study, a placebo looks like TAK-079 but does not have any medicine in
           it.

      Participants will not know which treatment they received, nor will their study doctors. This
      is to help make sure the results are more reliable.

      For each treatment, participants will receive injections just under the skin, once a week for
      8 weeks. The study doctors will check for side effects from the study treatments. The study
      doctors can stop or delay the injections in each participant if needed.

      Then, the study doctors will continue to check for side effects for up to 24 weeks after
      treatment. They will also check the clinical condition of the participants, including their
      autoantibody levels.
    

Eligibility criteria:

        Main Inclusion Criteria:

          1. Diagnosis of Myasthenia Gravis (MG) supported by a positive serologic test for
             anti-AChR or anti-MuSK antibodies at screening.

          2. Myasthenia Gravis Foundation of America (MGFA) clinical classification II to IV at
             screening.

          3. Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of 6 or greater at
             screening, with at least 4 points attributed to nonocular items.

          4. If receiving immunosuppressive drugs (ie, mycophenolate mofetil, methotrexate,
             cyclosporine, tacrolimus, cyclophosphamide), therapy must be ongoing for at least 6
             months, with stable dosing ongoing for at least 3 months before screening.
             Participants receiving azathioprine must be on a stable dose for at least 6 months
             before screening.

          5. 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.

          6. If receiving cholinesterase inhibitors, therapy with a stable dose is required at
             least 2 weeks before screening.

          7. 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 ± 1 steroid-sparing immunosuppressive drug (limited to azathioprine,
             mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus, or cyclophosphamide).
             Participants must be on at least one allowed background medication.

        Main Exclusion Criteria:

          1. Presence of a thymoma (previous history of a fully encapsulated thymoma removed ≥ 12
             months before screening is allowed) or history of invasive thymic malignancy unless
             deemed cured by adequate treatment with no evidence of recurrence for ≥ 5 years before
             screening.

          2. History of thymectomy within 12 months before screening.

          3. MGFA class I or V.

          4. Received intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), or
             plasmapheresis/plasma exchange within 4 weeks before screening, or an expectation that
             any therapy besides the participants standard background therapies may be used for
             treatment of MG (eg, a rescue therapy) between screening and dosing.

          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 participants suspected of having COPD or asthma.

          6. Received rituximab, belimumab, eculizumab, or any monoclonal antibody for
             immunomodulation within 6 months before first dosing. Participants with prior exposure
             to rituximab must have CD19 counts within the normal range at screening.

          7. Known autoimmune disease other than MG that could 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. Opportunistic infection ≤12 weeks before initial study dosing or 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
             prior to Day 1.