Efficacy and Safety Evaluation of Inebilizumab in Adults with Acetylcholine Receptor or Muscle-Specific Kinase Antibody-Positive Myasthenia Gravis
- Trial ID
- 2023-510006-40-00
- Protocol
- VIB0551.P3.S1
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess whether **inebilizumab** can reduce disability related to **Myasthenia Gravis** (MG), a chronic autoimmune neuromuscular disorder characterized by weakness and rapid fatigue of voluntary muscles. This is clinically relevant as reducing disability can significantly improve the daily functioning and quality of life for patients with MG.
Secondary objectives include:
- Evaluating whether inebilizumab can reduce the frequency of MG exacerbations.
- Assessing whether inebilizumab can improve MG-related quality of life.
- Evaluating the safety and tolerability of inebilizumab in MG patients.
- Characterizing the pharmacokinetic profile and immunogenicity of inebilizumab in patients with MG.
- Evaluating the effect of inebilizumab on corticosteroid usage.
- Assessing the ability of inebilizumab to elicit minimal symptom expression.
Participants
The clinical trial involves a total of **105 participants** diagnosed with **Myasthenia Gravis** due to either acetylcholine receptor antibodies (AChR) or muscle-specific kinase antibodies (MuSK). The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a diagnosis of Myasthenia Gravis with anti-AChR or anti-MuSK antibodies and a classification within the MGFA Clinical Classification Class II, III, or IV. The trial population is characterized by a requirement for stable medication regimens, including corticosteroids or non-steroidal immunosuppressive therapies, with no recent dose increases. Lifestyle considerations such as diet and physical activity are not specified, but females of childbearing potential are required to use effective contraception. The study does not exclude vulnerable populations, indicating a broad inclusion strategy to assess the impact of inebilizumab on reducing MG-related disability.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, placebo-controlled Phase 3 study designed to evaluate the efficacy and safety of **inebilizumab** in adults diagnosed with **myasthenia gravis**. The trial aims to assess whether inebilizumab can reduce disability related to myasthenia gravis, specifically in patients with antibodies against acetylcholine receptors (AChR) or muscle-specific kinase (MuSK). The study is structured to include an open-label period following the initial double-blind phase. The trial is expected to run from August 2020 to November 2027, with a maximum treatment period of 48 weeks for each participant.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as MGFA Clinical Classification and MG-ADL scores. Following randomization, participants will receive either inebilizumab or placebo via **intravenous use**. The primary endpoint is the change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at Week 26. Secondary endpoints include changes in the Quantitative Myasthenia Gravis (QMG) score and other measures of clinical improvement and quality of life at Weeks 26 and 52.
Study visits will include regular follow-up assessments to monitor efficacy and safety, with key evaluations at Weeks 26 and 52. The end-of-study visit will conclude the participant's involvement, unless early termination is warranted due to adverse events, lack of efficacy, or withdrawal of consent. Participants are expected to be involved in the study for up to 48 weeks, with conditions for early termination including significant adverse reactions or non-compliance with study protocols.
Treatment
The clinical trial involves the administration of **Inebilizumab**, an experimental medication, to evaluate its efficacy and safety in adults with **Myasthenia Gravis**. **Inebilizumab** is provided as a **solution for injection** and is administered via **intravenous use**. The dosage regimen includes a maximum daily dose of 300 mg, with a total maximum dose of 3000 mg over the treatment period. The treatment duration is set for a maximum of 48 weeks. **Inebilizumab** is a protein-based therapeutic agent, specifically categorized under "Protein - Other". The product is identified by the sponsor product code **MEDI-551** and is not formulated for pediatric use.
In addition to the experimental treatment, the study includes a **placebo** comparator. The placebo is a 10 mL nominal solution containing 10 mM histidine/histidine hydrochloride, 75 mM sodium chloride, 106 mM (4% [w/v]) trehalose dihydrate, and 0.02% (w/v) polysorbate 80, with a pH of 6.0. This solution is also administered via **intravenous use**. The placebo is designed to match the experimental treatment in appearance and administration schedule to maintain the study's double-blind design. The placebo does not contain any active pharmaceutical ingredients and serves as a control to assess the efficacy of **Inebilizumab**.
Efficacy
The efficacy of **inebilizumab** in the treatment of Myasthenia Gravis will be assessed through a series of primary and secondary endpoints. The primary endpoint is the change from baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at Week 26 in the overall study population, which includes both AChR-Ab+ and MuSK-Ab+ populations. Secondary endpoints include key measures such as the change from baseline in the Quantitative Myasthenia Gravis (QMG) score at Week 26, both in the overall study population and specifically in the AChR-Ab+ and MuSK-Ab+ populations.
Additional secondary endpoints will evaluate various aspects of patient outcomes, including the proportion of subjects with a ≥3-point improvement in MG-ADL score at Week 26 without the use of rescue therapy, changes in MG-ADL and QMG scores at Week 52, and changes in the Myasthenia Gravis Composite (MGC) score and Myasthenia Gravis Quality of Life-15, revised score at Weeks 26 and 52. The Patient Global Impression of Change score and time to first MG exacerbation will also be assessed. Safety and tolerability will be monitored through the incidence of treatment-emergent adverse events and laboratory measurements. The study will also track the proportion of subjects achieving minimal symptom expression and those with steroid dose reductions.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Diagnosis of MG with anti-AChR or anti-MuSK antibody
- MGFA Clinical Classification Class II, III, or IV.
- MG-ADL score at the time of screening and randomization between 6 and 10 with > 50% of this score attributed to non-ocular items, or an MG-ADL score ≥ 11.
- QMG score ≥ 11 or greater at the time of screening and at randomizatio
- Subjects must be on: a. Corticosteroids only, with no dose increase within 4 weeks prior to randomization, or b. One allowed non-steroidal IST, with continuous use for ≥ 6 months prior to randomization and no dose increase within 4 months prior to randomization, or c. Combination of (1) corticosteroids with no dose increase within 4 weeks prior to randomization and (2) one allowed non-steroidal IST with continuous use for ≥ 6 months prior to randomization and no dose increase within 4 months prior to randomization. Allowed ISTs, alone or in combination with corticosteroids, are azathioprine, mycophenolate mofetil, and mycophenolic acid.
- Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective contraception method from the time of screening and for 6 months after the final dose of IP. Periodic abstinence, the rhythm method, or the withdrawal method is not an acceptable methods of contraception
Exclusion Criteria
- Thymectomy within the 12 months prior to baseline (Day 1) visit or planned thymectomy during the duration of the RCP.
- Receipt of the following medications or treatments at any time prior to randomization: a. Alemtuzumab, b. Total lymphoid irradiation, c. Bone marrow transplant, d. T-cell vaccination therapy, e. Natalizumab, 10. Receipt of rituximab, ocrelizumab, ofatumumab, obinutuzumab, inebilizumab, or any experimental B-cell depleting agent within the 6 months prior to Day 1, unless the subject has a CD19+ B-cell count ≥ 40 cells/μL according to the central laboratory at screening. 11. Receipt of Leflunomide within 1 year prior to Day 1. 12. Receipt of the following within the 3 months prior to Day 1: a. Tocilizumab, b. Belimumab, c. Eculizumab, d. Cyclophosphamide, e. Ravulizumab, f. Neonatal Fc receptor blockers (efgartigimod alfa) g. Abatacept, h. Etanercept, i. Mitoxantrone, j. Sirolimus
- Receipt of the following within the 4 weeks prior to Day 1: a. Cyclosporine (except eye drops) b. Tacrolimus (except topical) (tacrolimus ≤ 3 mg/day is allowed in Japan only; see inclusion criterion 7C) c. Methotrexate d. Intravenous immunoglobulin (IVIg) or SC Ig e. PLEX treatment f. Thalidomide g. Tofacitinib
- Current use of: a. Corticosteroids (prednisone > 40 mg/day or > 80 mg over a 2-day period, or equivalent dose of other corticosteroids) b. Acetylcholinesterase inhibitors (pyridostigmine > 480 mg/day) or unstable dose in the 2 weeks prior to Day 1 c. Azathioprine > 3 mg/kg/day d. Mycophenolate mofetil > 3 g/day or mycophenolic acid > 1440 mg/day e. Any IST, alone or in combination with corticosteroids, except for azathioprine, mycophenolate mofetil, and mycophenolic acid.
- Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 half-lives of the investigational treatment, whichever is longer, prior to Day 1.
- Receipt of a live attenuated vaccine within 4 weeks prior to randomization. Administration of inactivated (killed) vaccines is acceptable.
- History of untreated hepatitis C infection, or positive antibody test for hepatitis C virus (HCV) unless patient is considered to be cured following antiviral therapy and has a HCV viral load below the limit of detection ≥ 24 weeks after completion of treatment at site or central lab
- Hospitalization for any reason < 30 days prior to randomization
- Current or recent myasthenia gravis exacerbationdeterioration that has not returned to baseline/resolved within at least 30 days prior to randomization.
- History of untreated hepatitis C infection, or positive antibody test for hepatitis C virus (HCV) unless the subject is considered to be cured following antiviral therapy and has an HCV viral load below the limit of detection ≥ 24 weeks after completion of treatment at site or central lab.
- Hospitalization for any reason < 30 days prior to randomization.
- Current or recent MG deterioration that has not returned to baseline/resolved within ≥ 30 days prior to randomization.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 03 Aug 2020 | 25 |
 Germany | Not Recruiting | 03 Aug 2020 | 25 |
 Italy | Not Recruiting | 03 Aug 2020 | 25 |
 Poland | Not Recruiting | 03 Aug 2020 | 25 |
 Spain | Not Recruiting | 03 Aug 2020 | 25 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
INEBILIZUMAB | Test | — | INTRAVENOUS USE | 300 | 48 | SUB189141 |
10 mL (nominal) solution containing 10 mM histidine/histidine hydrochloride, 75 mM sodium chloride, 106 mM (4% [w/v]) trehalose dihydrate, and 0.02% (w/v) polysorbate 80, pH 6.0 | Placebo | N/A | INTRAVENOUS USE | 300 | 48 | N/A |