Clinical trial NCT04159805: A Study of TAK-079 in People With Generalized Myasthenia Gravis
Official title: A Phase 2, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Efficacy of TAK-079 in Patients With Generalized Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myasthenia Gravis
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-11-12
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Myasthenia gravis (MG) is an autoimmune disorder in which autoantibodies, such as those targeting the nicotinic acetylcholine receptor (AChR) or muscle specific kinase (MuSK), interfere with neuromuscular transmission, resulting in fatigue and weakness.

The drug being tested in this study is called TAK-079. TAK-079 is being tested to treat people who have generalized myasthenia gravis.

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.

Primary outcomes:
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Grade 3 or Higher TEAEs, and Adverse Event (AE) Leading to TAK-079 Discontinuation
timeFrame: From signing the informed consent form up to end of long-term follow-up (up to Week 32)
Secondary outcomes:
measure: Change From Baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale Score
timeFrame: Baseline up to Week 32
measure: Change From Baseline in Quantitative Myasthenia Gravis (QMG) Scale Score
timeFrame: Baseline up to Week 32
measure: Change From Baseline in Myasthenia Gravis Composite (MGC) Scale Score
timeFrame: Baseline up to Week 32
measure: Change From Baseline in Revised 15-item Myasthenia Gravis Quality of Life Scale (MG-QoL15r) Scale Score
timeFrame: Baseline up to Week 32
measure: Change From Baseline in Anti-acetylcholine Receptor (AChR) Antibody Levels
timeFrame: Baseline up to Week 32
measure: Change From Baseline in Anti- Muscle-specific Tyrosine Kinase (MuSK) Titer Levels
timeFrame: Baseline up to Week 32
measure: Percentage of Participants With 2-point Reduction in MG-ADL Total Score
timeFrame: At Weeks 4, 6, 8, 10, 12, 14, 16, 20, 24, 28 and 32
measure: Percentage of Participants With 3-point Reduction in QMG Total Score
timeFrame: At Weeks 4, 6, 8, 10, 12, 14, 16, 20, 24, 28 and 32
measure: Percentage of Participants With 3-point Reduction in MGC Total Score
timeFrame: At Weeks 4, 6, 8, 10, 12, 14, 16, 20, 24, 28 and 32
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Medical Center
state: Arizona
city: Palo Alto
country: United States
facility: Stanford Neuroscience Health Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Boca Raton
country: United States
facility: SFM Clinical Research, LLC
state: Florida
city: Maitland
country: United States
facility: Neurology Associates PA
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center Inc
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Northbrook
country: United States
facility: Consultants In Neurology
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Columbia
country: United States
facility: Neurology and Sleep Disorders Clinic
state: Missouri
city: New York
country: United States
facility: Hospital For Special Surgery
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas HealthCare System Neurosciences Institute-Neurology
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Austin
country: United States
facility: Austin Neuromuscular Center
state: Texas
city: Dallas
country: United States
facility: The University of Texas South Western Medical Center
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants PA
state: Texas
city: Milwaukee
country: United States
facility: Center for Neurological Disorders
state: Wisconsin
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin, Inc.
state: Wisconsin
city: Calgary
country: Canada
facility: The Governors of the University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital (VGH)
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
state: Lazio
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Genova
country: Italy
facility: IRCCS AOU San Martino
city: Milano
country: Italy
facility: Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
city: Rome
country: Italy
facility: Azienda Ospedaliera Sant'andrea
city: Bydgoszcz
country: Poland
facility: Neurocentrum Bydgoszcz sp. z o.o.
state: Kujawsko-pomorskie
city: Krakow
country: Poland
facility: Centrum Neurologii Klinicznej Sp. z o.o.
state: Malopolskie
city: Warsaw
country: Poland
facility: Centrum Medyczne NeuroProtect
city: Warszawa
country: Poland
facility: Centrum Medyczne Warszawa - PRATIA - PPDS
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia - PPDS
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Nis
country: Serbia
facility: Clinical Center Nis
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: