A Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Patients with Generalized Myasthenia Gravis

• Register: EUCTR
• Last refreshed on: 30 August 2021
• Main ID: EUCTR2020-004436-21-IT
• Date of registration: 08/06/2021
• Prospective Registration: No
• Primary sponsor: F. HOFFMANN - LA ROCHE LTD.
• Public title: A Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Satralizumab in Patients with Generalized Myasthenia Gravis
• Scientific title: A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE EFFICACY, SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SATRALIZUMAB IN PATIENTS WITH GENERALIZED MYASTHENIA GRAVIS - -
• Date of first enrolment: 21/05/2021
• Target sample size: 240
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004436-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Brazil, Canada, China, Czechia, Denmark, France, Germany, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Turkey, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: Genentech Inc. c/o F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
• Age >=12 years at time of signing Informed Consent Form
• Confirmed diagnosis of gMG
• MGFA class II, III or IV at screening
• A total MG-ADL score of >=5 points at screening with more than 50% of this score attributed to non-ocular items
• Ongoing gMG treatment at a stable dose
• For female patients of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception during the treatment period and for at least 3 months after the final dose of satralizumab

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 208
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion criteria:
Excl Criteria Related to Myasthenia Gravis(MG):
•History of thymic cysts, thymoma, thymic carcinoma or other neoplasm of the thymus as defined by the 2015 WHO classification of tumors of the thymus unless deemed cured by adequate treatment with no evidence of recurrence for >=5 years before screen
•History of thymectomy within 12 months prior to screen
•Ocular MG (Myasthenia Gravis Foundation of America[MGFA] Class I)
•Myasthenic crisis within the last 3 months prior to screen(MGFA Class V)
•Known disease other than gMG that would interfere with the course and conduct of the study
Excl Criteria Related to Previous or Concomitant Therapy:
•Use of IVIg within 8 weeks prior to randomization(Day 1)
•Use of PE within 8 weeks prior to randomization(Day 1)
•Treat with IL-6 inhibitory therapy(e.g., tocilizumab)at any time
•Treat with total body irradiation,or bone marrow transplantation at any time
•Treat with B and/or T cell-depleting agents
•For pt with prior exposure to anti-CD20 agents, CD19 counts below the normal range, as assessed by the central laboratory at screen or <6 months since last anti-CD20 treat till screen
•Treat with eculizumab within 6 months prior to screen
•Treat with neonatal Fc receptor antagonists or anti-B-lymphocyte stimulator monoclonal antibody at any time
•Treat with cyclophosphamide IV within 6 months prior to screen
•Treatment with oral cyclophosphamide at any time
•Treat with methotrexate within 8 weeks prior to screen
•Treat with any investigational agent within 24 weeks prior to screen or 5 drug-elimination half-lives of the investigational drug (whichever is longer)
•Use of more than one IST as background therapy except for the combination of an oral corticosteroids (OCS) with another permitted IST drug
General Safety Excl Criteria:
•Any surgical procedure (except for minor surgeries) within 4 weeks prior to baseline
•Planned surgical procedure (except minor surgeries) during the study
•Evidence of progressive multifocal leukoencephalopathy
•Evidence of serious uncontrolled concomitant diseases that may preclude pt participation
•Congenital or acquired immunodeficiency,including human immunodeficiency virus (HIV)infection
•Active or presence of recurrent bacterial,viral,fungal,mycobacterial infection or other infection,excluding fungal infection of nail beds or dental caries
•Infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks prior to baseline visit or oral anti-infective agents within 2 weeks prior to baseline visit
•Pos screening tests for hepatitis B and C
•History of drug or alcohol abuse within 1 year prior to baseline
•History of diverticulitis or concurrent severe gastrointestinal (GI) disorders that, in the investigator’s opinion,may lead to increased risk of complications such as GI perforation
•Evidence of latent or active tuberculosis
•Receipt of live or live attenuated vaccine within 6 weeks prior to baseline
•History of blood donation (1 unit or more),plasma donation or platelet donation within 90 days prior to screening and Day 1
•History of malignancy within the last 5 years,including solid tumors,hematologic malignancies and in situ carcinoma
•History of severe allergic reaction to a biologic agent
•Active suicidal ideation within 6 months prior to screening or history of suicide attempt within 3 years prior to screening
•Any serious medical condition or abnormality in clinical laboratory tests that,in the investigator's judgment,precludes the pt's s

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Generalized Myasthenia Gravis (gMG)
MedDRA version: 21.1 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: Satralizumab
Product Code: [RO5333787]
Pharmaceutical Form: Injection
INN or Proposed INN: SATRALIZUMAB
Current Sponsor code: RO5333787
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. From baseline to Week 24

Primary end point(s): 1. Mean change from baseline in total MG-ADL score (AChR+ population) Week 24

Main Objective: • To evaluate the efficacy of satralizumab versus placebo on function in daily life in the acetylcholine receptor antibody seropositive (AChR+) population

Secondary Objective: • To evaluate the efficacy of satralizumab versus placebo on function in daily life in the overall population (OP)
• To evaluate the efficacy of satralizumab versus placebo in the AChR+ and OP on QMG, QoL, Fatigue, Clinical status and Disease severity
• To evaluate the durability of the efficacy of satralizumab versus placebo in the AChR+ population and the OP
• To evaluate the safety of satralizumab versus placebo
• To confirm target engagement and pathway inhibition in response to satralizumab
• To investigate the pharmacokinetics (PK) of satralizumab
• To evaluate the immune response to satralizumab

Secondary Outcome(s)

Secondary end point(s): 1. Mean change from baseline in total MG-ADL score (OP population)
2. Mean change from baseline in QMG score, MG-QOL 15r total score and Neuro-QoL Fatigue Subscale total score
3. Mean change from baseline in total Myasthenia Gravis Composite (MGC) score
4. Percentage of patients with a >=2-point reduction from baseline in total MG-ADL score
5. Percentage of patients with a >=3-point reduction from baseline in QMG score
6. Percentage of patients with a >=3-point reduction from baseline in total MGC score
7. Proportion of patients who have achieved minimal disease manifestation (total MG-ADL score of 0 or 1)
8. Proportion of patients with at least one gMG-related exacerbation and receiving rescue therapy between baseline and Week 24
9. Annualized rate of gMG-related exacerbations
10. Duration (average number of consecutive months) of meaningful improvement, defined as >=2-point reduction from baseline in total MG-ADL score
11. Absolute values of biomarkers interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R)
12. Serum concentrations of satralizumab at specified timepoints
13. Apparent clearance (CL/F) of satralizumab at specified timepoints
14. Volume of distribution (V/F) of satralizumab at specified timepoints
15. Area under the concentration-time curve (AUC) of satralizumab at specified timepoints
16. Incidence of ADAs against satralizumab during the study
17. Prevalence of anti-drug antibodies (ADAs) against satralizumab at baseline
18. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0 grading
19. Change from baseline in targeted vital signs, ECG results, physical examination findings, targeted clinical laboratory test results, and suicidality

Timepoint(s) of evaluation of this end point: 1-3. Baseline and Week 24
4-8. At Week 24
9. Baseline to Week 24
10-11. Baseline to Week 24
12-16. At Day 1, Weeks 2, 4, 8, 12, 16, 20, and 24
17. Predefined timepoints
18-19. Baseline to 24 weeks

Secondary ID(s)

2020-004436-21-DK

WN42636

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 14/04/2021
Contact: