Myasthenia Gravis
Conditions
Keywords
UCB7665, Myasthenia Gravis
Brief summary
The purpose of the study is to evaluate the clinical efficacy of UCB7665 as a chronic-intermittent treatment in subjects with generalized myasthenia gravis (MG) who are classified as moderate to severe.
Interventions
DRUGUCB7665
UCB7665 will be administered in 2 different dosages (dose 1 and dose 2). UCB7665 (INN: Rozanolixizumab) is a humanized monoclonal antibody that is being developed for treatment of IgG autoantibody-mediated conditions such as myasthenia gravis (MG)
OTHERPlacebo
Placebo will be administered in period 1 of dosage regimen 2.
Sponsors
UCB Biopharma S.P.R.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is an Investigator- and Subject-Blind study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has a well-documented diagnosis of myasthenia gravis (MG) at Visit 1 (Screening), based on subject history and supported by previous evaluations * Subject would currently be considered for treatment with immunological therapy (immunoglobulin/plasma exchange (IVIG/PLEX)) by the investigator * Subject has a well-documented record of autoantibodies against anti-acetylcholine receptor (Anti-AChR) or anti-muscle specific kinase (Anti-MuSK) prior to Screening * Female subjects must either be: postmenopausal, permanently sterilized or if childbearing potential applicable will use a highly effective method of birth control * Male subjects must be willing to use a method of contraception
Exclusion criteria
* Subject has previously received treatment in this study or subject has previously been exposed to UCB7665 * Subject has participated in another study of an investigational medicinal product (IMP; or a medical device) within the previous 30 days of Screening or is currently participating in another study of an investigational medicinal product (IMP; or a medical device) * Subject has a known hypersensitivity to any components of the IMP * Subject has a history of hyperprolinemia, since L-proline is a constituent of the UCB7665 IMP * Subjects with Myasthenia Gravis (MG) only affecting the ocular muscles * Subjects with severe weakness affecting oropharyngeal or respiratory muscles, or who have myasthenic crisis at Screening or impending crisis * Subject has quantitative myasthenia gravis (QMG) score of \<11 at Baseline * Subject has a serum total immunoglobulin G (IgG) level \<= 6g/L at Screening * Absolute neutrophil count \<1500 cells/mm\^3 * Subject has any medical condition (acute or chronic illness) or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study * Subject has any laboratory abnormality that, in the opinion of the investigator, is clinically significant, has not resolved at randomization, and could jeopardize or would compromise the subject's ability to participate in this study * Subject has received a live vaccination within 8 weeks prior to the Baseline Visit; or intends to have a live vaccination during the course of the study or within 7 weeks following the final dose of IMP * Subject has received any experimental biological agent within or outside of a clinical study in the past 3 months or within 5 half-lives prior to Baseline (whichever is longer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score to Visit 9 | From Baseline to Visit 9 (up to Day 29) | The total QMG score was obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3). The score ranges from 0 to 39, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Myasthenia Gravis-Composite Score to Visit 9 | From Baseline to Visit 9 (up to Day 29) | The total Myasthenia Gravis (MG)-composite score was obtained by summing the responses to each individual item (10 items; Grade: 0-9 depending on item). The score ranges from 0 to 50, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
| Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MGADL) Score to Visit 9 | From Baseline to Visit 9 (up to Day 29) | The total MGDAL score was obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3). The score ranges from 0 to 24, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. |
Countries
Belgium, Canada, Czechia, Denmark, Germany, Spain, United States
Participant flow
Recruitment details
The study started to enroll patients in May 2017 and concluded in August 2018.
Pre-assignment details
The Participant Flow refers to the Randomized Set (RS) which consisted of all participants randomized into the study at the first randomization visit.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received 3 doses of placebo in Dosing Period 1 and then were re-randomized into Dosing Period 2 to receive 3 doses of UCB7665 (7 mg/kg or 4 mg/kg). | 22 |
| UCB7665 (7 mg/kg) Participants received 3 doses of UCB7665 (7 mg/kg) in Dosing Period 1 and then were re-randomized into Dosing Period 2 to receive 3 doses of UCB7665 (7 mg/kg or 4 mg/kg). | 21 |
| Total Title | 43 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Dosing Period 1 | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
| Dosing Period 2 | Adverse Event | 0 | 0 | 3 | 0 | 0 | 0 |
| Observation Period | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | UCB7665 (7 mg/kg) | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 3 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 18 Participants | 32 Participants |
| Age, Continuous | 53.3 years STANDARD_DEVIATION 15.7 | 50.5 years STANDARD_DEVIATION 14.7 | 51.9 years STANDARD_DEVIATION 15.1 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other/mixed | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 19 Participants | 20 Participants | 39 Participants |
| Sex: Female, Male Female | 14 Participants | 13 Participants | 27 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 21 | 0 / 11 | 0 / 11 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 7 / 22 | 13 / 21 | 7 / 11 | 9 / 11 | 8 / 10 | 9 / 10 |
| serious Total, serious adverse events | 2 / 22 | 0 / 21 | 3 / 11 | 1 / 11 | 1 / 10 | 0 / 10 |
Outcome results
Primary
Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score to Visit 9
The total QMG score was obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3). The score ranges from 0 to 39, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Visit 9 (up to Day 29)
Population: The FAS consisted of all participants in the SS who had a Baseline and at least 1 post-Baseline QMG measurement during Dosing Period 1 (up to and including Visit 9, ie, Day 29).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score to Visit 9 | -1.2 scores on a scale | Standard Error 0.6 |
| UCB7665 (7 mg/kg) (FAS) | Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score to Visit 9 | -1.8 scores on a scale | Standard Error 0.6 |
Comparison: Mixed Model Repeated Measures (MMRM) Analysis of Covariance (ANCOVA) model included fixed terms for treatment group, visit, interaction between treatment group and visit, covariate of Baseline QMG score, and random effect for participant.~The differences presented was 'UCB7665 (7 mg/kg) minus Placebo'.p-value: =0.221MMRM
Secondary
Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MGADL) Score to Visit 9
The total MGDAL score was obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3). The score ranges from 0 to 24, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Visit 9 (up to Day 29)
Population: The FAS consisted of all participants in the SS who had a Baseline and at least 1 post-Baseline QMG measurement during Dosing Period 1 (up to and including Visit 9, ie, Day 29).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MGADL) Score to Visit 9 | -0.4 scores on a scale | Standard Error 0.5 |
| UCB7665 (7 mg/kg) (FAS) | Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MGADL) Score to Visit 9 | -1.8 scores on a scale | Standard Error 0.5 |
Comparison: ANCOVA model included fixed terms for treatment group, covariate of Baseline MGADL score.p-value: =0.036ANCOVA
Secondary
Change From Baseline in Myasthenia Gravis-Composite Score to Visit 9
The total Myasthenia Gravis (MG)-composite score was obtained by summing the responses to each individual item (10 items; Grade: 0-9 depending on item). The score ranges from 0 to 50, with lower scores indicating lower disease activity. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening.
Time frame: From Baseline to Visit 9 (up to Day 29)
Population: The FAS consisted of all participants in the SS who had a Baseline and at least 1 post-Baseline QMG measurement during Dosing Period 1 (up to and including Visit 9, ie, Day 29).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (FAS) | Change From Baseline in Myasthenia Gravis-Composite Score to Visit 9 | -1.2 scores on a scale | Standard Error 0.9 |
| UCB7665 (7 mg/kg) (FAS) | Change From Baseline in Myasthenia Gravis-Composite Score to Visit 9 | -3.1 scores on a scale | Standard Error 0.9 |
Comparison: MMRM ANCOVA model included fixed terms for treatment group, visit, interaction between treatment group and visit, covariate of Baseline MG-composite score, and random effect for participant.~The differences presented was 'UCB7665 (7 mg/kg) minus Placebo'.p-value: =0.089MMRM