A Study of TAK-079 in People With Generalized Myasthenia Gravis

Myasthenia Gravis Clinical Trial

Official title:

A Phase 2, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Efficacy of TAK-079 in Patients With Generalized Myasthenia Gravis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04159805
• Other study ID #: TAK-079-1005
• Secondary ID: 2019-003383-47
• Status: Completed
• Phase: Phase 2
• Start date: January 14, 2020
• Est. completion date: July 12, 2022

Study information

• Verified date: May 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: July 12, 2022
• Est. primary completion date: July 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis

Intervention

Drug:
• TAK-079
TAK-079 subcutaneous injection
• TAK-079 Placebo
TAK-079 placebo-matching subcutaneous injection

Locations

Country	Name	City	State
Canada	The Governors of the University of Calgary	Calgary	Alberta
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Vancouver General Hospital (VGH)	Vancouver	British Columbia
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	IRCCS AOU San Martino	Genova
Italy	Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta	Milano
Italy	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio
Italy	Azienda Ospedaliera Sant'andrea	Rome
Poland	Neurocentrum Bydgoszcz sp. z o.o.	Bydgoszcz	Kujawsko-pomorskie
Poland	Centrum Neurologii Klinicznej Sp. z o.o.	Krakow	Malopolskie
Poland	Centrum Medyczne NeuroProtect	Warsaw
Poland	Centrum Medyczne Warszawa - PRATIA - PPDS	Warszawa
Serbia	Clinical Center of Serbia - PPDS	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Clinical Center Nis	Nis
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario La Paz - PPDS	Madrid
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
United States	Augusta University	Augusta	Georgia
United States	University of Colorado Hospital	Aurora	Colorado
United States	Austin Neuromuscular Center	Austin	Texas
United States	SFM Clinical Research, LLC	Boca Raton	Florida
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Carolinas HealthCare System Neurosciences Institute-Neurology	Charlotte	North Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Neurology and Sleep Disorders Clinic	Columbia	Missouri
United States	Ohio State University Medical Center	Columbus	Ohio
United States	The University of Texas South Western Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Wayne State University	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Michigan State University	East Lansing	Michigan
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Neurology Associates PA	Maitland	Florida
United States	Center for Neurological Disorders	Milwaukee	Wisconsin
United States	The Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin
United States	Hospital For Special Surgery	New York	New York
United States	Consultants In Neurology	Northbrook	Illinois
United States	Stanford Neuroscience Health Center	Palo Alto	California
United States	Medsol Clinical Research Center Inc	Port Charlotte	Florida
United States	Central Texas Neurology Consultants PA	Round Rock	Texas
United States	University of California Davis Medical Center	Sacramento	California
United States	University of California Davis Medical Center	Sacramento	California
United States	The University of Arizona Medical Center	Tucson	Arizona
United States	George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

United States,  Canada,  Italy,  Poland,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	AE is defined as any untoward medical occurrence in clinical investigation participant administered drug; it does not necessarily have to have causal relationship with this treatment. TEAE is defined as AE with onset that occurs after receiving study drug. SAE is an adverse event resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Severity of TEAEs was graded using National cancer institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 definitions of Grade 1 through Grade 5 wherein Grade 1=mild symptoms, Grade 2=moderate symptoms, Grade 3=Severe or medically significant but not immediately life-threatening, Grade 4=life-threatening consequences and Grade 5=death related to AEs. Percentages are rounded off to whole number at single decimal.	From signing the informed consent form up to end of long-term follow-up (up to Week 32)
Secondary	Change From Baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale Score	Participant-reported scale to assess MG symptoms to evaluate capacity to perform activities of daily living. Each question is graded on a 4-point scale from 0=normal to 3=severe with a total score of 0 to 24; the higher score indicates greater functional impairment and disability. Negative change indicates improvement. Mixed-effects model for repeated measures (MMRM) was used for the analysis.	Baseline up to Week 32
Secondary	Change From Baseline in Quantitative Myasthenia Gravis (QMG) Scale Score	Physician-reported scale to assess MG disease severity by quantifying several body functions by physical exam. Each question is graded on a 4-point scale from 0=normal to 3=severe with a total score of 0 to 39; the higher score indicates greater disease burden. Negative change indicates improvement. MMRM was used for the analysis.	Baseline up to Week 32
Secondary	Change From Baseline in Myasthenia Gravis Composite (MGC) Scale Score	An assessment scale of MG disease activity based on a combination of participant- and physician-reported items. Items are scored based on 4 potential levels of impact: normal, mild, moderate, or severe with a total score of 0 to 50; the higher score indicates worse MG disease activity. Negative change indicates improvement. MMRM was used for the analysis.	Baseline up to Week 32
Secondary	Change From Baseline in Revised 15-item Myasthenia Gravis Quality of Life Scale (MG-QoL15r) Scale Score	A participant-reported score that assesses the participant's perception of impairment and disability and the degree to which the participant tolerates disease manifestations. Each question is graded on a 3-point scale from 0=normal to 2=severe with a total score of 0 to 30; the higher score indicates worse MG disease activity. Negative change indicates improvement. MMRM was used for the analysis.	Baseline up to Week 32
Secondary	Change From Baseline in Anti-acetylcholine Receptor (AChR) Antibody Levels	Clinical laboratory evaluations of anti-AChR antibodies were tested to monitor disease activity. MMRM was used for the analysis.	Baseline up to Week 32
Secondary	Change From Baseline in Anti- Muscle-specific Tyrosine Kinase (MuSK) Titer Levels	Clinical laboratory evaluations of anti-MuSK antibodies were tested to monitor disease activity. Data is reported for participants who were positive for anti-MuSK antibodies at baseline.	Baseline up to Week 32
Secondary	Percentage of Participants With 2-point Reduction in MG-ADL Total Score	The percentage of responders with at least a 2-point reduction in MG-ADL total score from baseline is reported. MG-ADL is a participant-reported scale to assess MG symptoms to evaluate capacity to perform activities of daily living. Each question is graded on a 4-point scale from 0=normal to 3=severe with a total score of 0 to 24; the higher score indicates greater functional impairment and disability. Percentages are rounded off to whole number at the nearest decimal.	At Weeks 4, 6, 8, 10, 12, 14, 16, 20, 24, 28 and 32
Secondary	Percentage of Participants With 3-point Reduction in QMG Total Score	The percentage of responders with at least a 3-point reduction in QMG total score from baseline is reported. QMG is a physician-reported scale to assess MG disease severity by quantifying several body functions by physical exam. Each question is graded on a 4-point scale from 0=normal to 3=severe with a total score of 0 to 39; the higher score indicates greater disease burden. Percentages are rounded off to whole number at the nearest decimal.	At Weeks 4, 6, 8, 10, 12, 14, 16, 20, 24, 28 and 32
Secondary	Percentage of Participants With 3-point Reduction in MGC Total Score	The percentage of responders with at least a 3-point reduction in MGC total score from baseline is reported. MGC is an assessment scale of MG disease activity based on a combination of participant- and physician-reported items. Items are scored based on 4 potential levels of impact: normal, mild, moderate, or severe with a total score of 0 to 50; the higher score indicates worse MG disease activity. Percentages are rounded off to whole number at the nearest decimal.	At Weeks 4, 6, 8, 10, 12, 14, 16, 20, 24, 28 and 32

External Links

•   To obtain more information on the study, click here/on this link