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

• Register: EUCTR
• Last refreshed on: 14 October 2024
• Main ID: EUCTR2020-004436-21-DK
• Date of registration: 11/03/2021
• Prospective Registration: Yes
• 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: 11/08/2021
• Target sample size: 185
• Recruitment status: Not Recruiting
• 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 (or >= 18 years in France) at time of signing Informed Consent Form
• Confirmed diagnosis of gMG meeting the following criteria:
- Documented history of myasthenic weakness
- MG severity of MGFA Class II, III, or IV (Patients with MG Class IV at participating sites in France are excluded from the study) at screening
- The confirmation of the diagnosis has to be documented and supported by positive serologic test for one of the three antibody types: anti- AChR, anti- MuSK or anti- LRP4 at screening (antibody status must be confirmed by the central laboratory for all antibody types). For sites in Germany and the Netherlands, confirmation of the diagnosis has to be documented and supported by pre-existing positive serologic test results for one of the three antibody types (anti-AChR, anti-MuSK, or anti-LRP4), which must have been ordered by a health care professional (HCP) for the patient as part of the patient’s historical SOC
• 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 and not exceeding the maximum protocol allowed doses
• No contraindication to at least one of the rescue treatments: IVIg, PE, or high dose corticosteroids
• 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: 6
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 147
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion criteria:
Exclusion 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 screening
• History of thymectomy within 6 months prior to screening
• Ocular MG (Myasthenia Gravis Foundation of America [MGFA] Class I). In France, MGFA Class IV MG at screening
• Use of IVIg or subcutaneous immunoglobulin (SCIg) within 6 weeks prior to randomization/Day 1
• Use of PE within 8 weeks prior to randomization/Day 1
• Any surgical procedure (except for non-ophthalmic minor surgeries) within 4 weeks prior to screening and planned surgical procedure (except non-ophthalmic minor surgeries) during the study




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: Solution for injection in pre-filled syringe
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

Product Name: Satralizumab
Product Code: Ro 533-3787/F01-06
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: SATRALIZUMAB
Current Sponsor code: RO5333787
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-

Primary Outcome(s)

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

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

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

Secondary Objective: • Evaluate the efficacy of satralizumab vs placebo on function in daily life in the overall population (OP)
• Evaluate the efficacy of satralizumab vs placebo in the AChR+ population and OP on function in daily life, QMG, QoL, Fatigue, Clinical status and Disease severity
• Evaluate the durability of the efficacy of satralizumab vs placebo in the AChR+ population and the OP
• Evaluate the safety of satralizumab vs placebo
• Confirm target engagement and pathway inhibition in response to satralizumab
• Investigate the PK of satralizumab by evaluating plasma exposure over 24 weeks
• Evaluate the immune response to satralizumab
• Evaluate the long-term safety and tolerability of satralizumab
• Assess the efficacy of satralizumab in the AChR + population and OP
• Assess the effect of satralizumab on steroid/IST/AChEI dose modification in the AChR + population and OP
• Investigate the pharmacokinetics of satralizumab by evaluating plasma exposure in the OLE

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 at Week 24
7. Proportion of patients who have achieved minimal disease manifestation (total MG-ADL score of 0 or 1) at Week 24
8. Proportion of patients with at least one gMG-related exacerbation and receiving rescue therapy between baseline and Week 24
9. Proportion of patients receiving rescue therapy between baseline and Week 24
10. Annualized rate of gMG-related exacerbations
11. Duration (average number of consecutive months) of meaningful improvement, defined as >=2-point reduction from baseline in total MG-ADL score
12. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0 grading
13. Change from baseline in targeted vital signs, ECG results, physical examination findings, targeted clinical laboratory test results, and suicidality
14. Absolute values and change from baseline in serum levels of biomarkers IL- 6 and sIL- 6R
15. Serum concentrations of satralizumab (mean and SD of Ctrough) at specified timepoints
16. Estimates of primary PK parameters (e.g., CL/F and V/F) and secondary PK parameters (e.g., AUC) derived using population-PK modeling
17. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study
18. Mean change from active treatment baseline in:
• MG ADL total score
• QMG score
• MGC score
• MG QOL 15r score
19. Percentage of responders based on:
• >= 2-point reduction in total MG ADL score or
• >= 3-point reduction in QMG score or
• >= 3-point reduction in total MGC score
20. Proportion of time and duration that patients show a meaningful improvement, defined as a = 2 point reduction from active treatment baseline in total MG ADL score
21. Number and severity of gMG-related exacerbations
22. The proportion of patients who maintain clinical response without increase in symptomatic medication dose and are able to reduce corticosteroid dose or withdraw from corticosteroid or IST during the OLE
23. Serum concentrations of satralizumab (mean and SD of Ctrough) during the OLE
24. Estimates of primary PK parameters (e.g., CL/F and V/F) and secondary PK parameters (e.g., AUC) derived using population-PK modeling during the OLE
25. Prevalence of ADAs at baseline and incidence of ADAs during the OLE
26. Absolute values and change from baseline in serum levels of PD biomarkers IL- 6 and sIL- 6R

Timepoint(s) of evaluation of this end point: 1-3, 8-9. Baseline and Week 24.
4-7, 18-20. At Week 24.
10-14, 21-22, 26: Baseline to Week 24.
15-16, 23-24. At Day 1, Weeks 2, 4, 8, 12, 16, 20, and 24.
17, 25. Predefined timepoints.

Secondary ID(s)

WN42636

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 11/08/2021
Contact: