A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis

Sponsor

UCB Biopharma SRL (Industry)

Overall Status

Completed

CT.gov ID

NCT03971422

Collaborator

(none)

200

Enrollment

Locations

Arms

28.8

Actual Duration (Months)

2.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the MycarinGstudy is to demonstrate the clinical efficacy and to assess safety and tolerability of rozanolixizumab in patients with generalized myasthenia gravis (MG).

Condition or Disease	Intervention/Treatment	Phase
Generalized Myasthenia Gravis	Drug: Rozanolixizumab Other: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis

Actual Study Start Date :

Jun 3, 2019

Actual Primary Completion Date :

Aug 31, 2021

Actual Study Completion Date :

Oct 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dosage Regimen 1 Study participants randomized to dosage regimen 1 will receive assigned dosage of rozanolixizumab at pre-specified time points during Treatment Period.	Drug: Rozanolixizumab Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2. Other Names: UCB7665
Experimental: Dosage Regimen 2 Study participants randomized to dosage regimen 2 will receive assigned dosage of rozanolixizumab at pre-specified time points during Treatment Period.	Drug: Rozanolixizumab Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2. Other Names: UCB7665
Placebo Comparator: Placebo Study participants randomized to this arm will receive placebo.	Other: Placebo Subjects will receive placebo at pre-specified time points. Other Names: PBO

Arm

Intervention/Treatment

Experimental: Dosage Regimen 1

Study participants randomized to dosage regimen 1 will receive assigned dosage of rozanolixizumab at pre-specified time points during Treatment Period.

Drug: Rozanolixizumab

Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.

Other Names:

UCB7665

Experimental: Dosage Regimen 2

Study participants randomized to dosage regimen 2 will receive assigned dosage of rozanolixizumab at pre-specified time points during Treatment Period.

Drug: Rozanolixizumab

Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.

Other Names:

UCB7665

Placebo Comparator: Placebo

Study participants randomized to this arm will receive placebo.

Other: Placebo

Subjects will receive placebo at pre-specified time points.

Other Names:

PBO

Outcome Measures

Primary Outcome Measures

Change from Baseline to Day 43 (Visit 10) in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score [Baseline and Visit 10 (Day 43)]
The total MG-ADL score is obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3). The score ranges from 0 to 24, with a higher score indicating more disability.

Secondary Outcome Measures

Percentage of participants achieving Myasthenia Gravis-Activities of Daily Living (MG-ADL) response at Visit 10 [Visit 10 (Day 43)]
The total MG-ADL score is obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3). The score ranges from 0 to 24, with a higher score indicating more disability.
Change from Baseline to Day 43 (Visit 10) in Myasthenia Gravis-Composite (MG-C) score [Baseline and Visit 10 (Day 43)]
The total Myasthenia Gravis-Composite (MG-C) score is 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.
Change from Baseline to Day 43 (Visit 10) in Quantitative Myasthenia Gravis (QMG) score [Baseline and Visit 10 (Day 43)]
The total QMG score is 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.
Change from Baseline to Day 43 (Visit 10) in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Muscle Weakness Fatigability' score [Baseline and Visit 10 (Day 43)]
The MG symptoms PRO instrument consists of 42 items across 5 scales: ocular symptoms (items 1-5); bulbar symptoms (items 6-15); respiratory symptoms (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). The study participant will be asked to choose the response option that best describes the severity of ocular, bulbar, and respiratory symptoms over the past 7 days using a 4-point Likert scale ("none" to "severe") and how frequently they experience physical fatigue and muscle weakness fatigability over the past 7 days using a 5-point Likert scale ("none of the time" to "all of the time"), respectively.
Change from Baseline to Day 43 (Visit 10) in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Physical Fatigue' score [Baseline and Visit 10 (Day 43)]
The MG symptoms PRO instrument consists of 42 items across 5 scales: ocular symptoms (items 1-5); bulbar symptoms (items 6-15); respiratory symptoms (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). The study participant will be asked to choose the response option that best describes the severity of ocular, bulbar, and respiratory symptoms over the past 7 days using a 4-point Likert scale ("none" to "severe") and how frequently they experience physical fatigue and muscle weakness fatigability over the past 7 days using a 5-point Likert scale ("none of the time" to "all of the time"), respectively.
Change from Baseline to Day 43 (Visit 10) in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Bulbar Symptoms' score [Baseline and Visit 10 (Day 43)]
The MG symptoms PRO instrument consists of 42 items across 5 scales: ocular symptoms (items 1-5); bulbar symptoms (items 6-15); respiratory symptoms (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). The study participant will be asked to choose the response option that best describes the severity of ocular, bulbar, and respiratory symptoms over the past 7 days using a 4-point Likert scale ("none" to "severe") and how frequently they experience physical fatigue and muscle weakness fatigability over the past 7 days using a 5-point Likert scale ("none of the time" to "all of the time"), respectively.
Occurrence of treatment-emergent adverse events (TEAEs) [From Baseline until End of Study Visit (up to Week 14)]
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A treatment-emergent adverse event (TEAE) is defined as any event that was not present prior to the first administration of IMP or any unresolved event already present before the first administration of IMP that worsens in intensity following exposure to treatment.
Treatment-emergent adverse events (TEAEs) leading to withdrawal of investigational medicinal product (IMP) [From Baseline until End of Study Visit (up to Week 14)]
One of the secondary outcome measures is to assess safety and tolerability of the IMP in the MG patients. This can be measured by treatment-emergent adverse events (TEAEs) leading to withdrawal of IMP. A TEAE is defined as any event that was not present prior to the first administration of IMP or any unresolved event already present before the first administration of IMP that worsens in intensity following exposure to treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Study participant must be ≥18 years of age, at the time of signing the informed consent
Study participant has documented diagnosis of generalized myasthenia gravis (gMG) at Visit 1, based on study participant's history and supported by previous evaluations
Study participant has a confirmed positive record of autoantibodies against acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) at Screening (Visit 1).The presence of autoantibodies may be confirmed with repeat testing at Visit 1
Study participant has Myasthenia Gravis Foundation of America (MGFA) Class II to IVa at Visit 1
Study participant with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of at least 3 (with ≥3 points from non-ocular symptom) AND a quantitative myasthenia gravis (QMG) score of at least 11 at Visit 1 and at Baseline (Visit 2)
Study participant is considered for additional treatment such as intravenous immunoglobulin g (IVIg) or plasma exchange (PEX) by the Investigator

Exclusion Criteria:

Study participant has a known history of hyperprolinemia
Study participant has a clinically relevant active infection (eg, sepsis, pneumonia, or abscess) in the opinion of the Investigator, or had a serious infection (resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks prior to the first dose of investigational medicinal product (IMP)
Study participant with a known tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent tuberculosis infection (LTBI), or current/history of nontuberculous mycobacterial infection (NTMBI) will be excluded
Study participant has experienced hypersensitivity reaction after exposure to other anti-neonatal Fc receptor (FcRn) drugs
Study participant with severe (defined as Grade 3 on the Myasthenia Gravis-Activities of Daily Living (MG-ADL) scale) weakness affecting oropharyngeal or respiratory muscles, or who has myasthenic crisis or impending crisis at Visit 1 or Visit 2
Study participant has a history of a solid organ transplant or hematopoietic stem cell/marrow transplant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mg0003 50081	Phoenix	Arizona	United States	85013
2	Mg0003 50082	Scottsdale	Arizona	United States	85251
3	Mg0003 50072	Los Angeles	California	United States	90033
4	Mg0003 50092	Orange	California	United States	92868
5	Mg0003 50099	San Francisco	California	United States	94117
6	Mg0003 50088	Washington	District of Columbia	United States	20037
7	Mg0003 50122	Miami	Florida	United States	33136
8	Mg0003 50120	Miami	Florida	United States	33144
9	Mg0003 50073	Tampa	Florida	United States	33612
10	Mg0003 50075	Augusta	Georgia	United States	30912
11	Mg0003 50323	Honolulu	Hawaii	United States	96817
12	Mg0003 50109	Chicago	Illinois	United States	60637
13	Mg0003 50114	Indianapolis	Indiana	United States	46202
14	Mg0003 50074	Fairway	Kansas	United States	66205
15	Mg0003 50121	Lexington	Kentucky	United States	40536
16	Mg0003 50104	Rochester	Minnesota	United States	55905
17	Mg0003 50077	New York	New York	United States	10021
18	Mg0003 50117	Charlotte	North Carolina	United States	28204
19	Mg0003 50090	Winston-Salem	North Carolina	United States	27157
20	Mg0003 50076	Columbus	Ohio	United States	43210
21	Mg0003 50096	Philadelphia	Pennsylvania	United States	19104
22	Mg0003 50113	Houston	Texas	United States	77030
23	Mg0003 40121	Bruxelles		Belgium
24	Mg0003 50071	Edmonton		Canada
25	Mg0003 50066	Montréal		Canada
26	Mg0003 50124	Montréal		Canada
27	Mg0003 50070	Québec		Canada
28	Mg0003 50069	Toronto		Canada
29	Mg0003 40125	Ostrava		Czechia
30	Mg0003 40124	Praha 2		Czechia
31	Mg0003 40128	Aalborg		Denmark
32	Mg0003 40127	Aarhus n		Denmark
33	Mg0003 40126	Copenhagen		Denmark
34	Mg0003 40489	Odense		Denmark
35	Mg0003 40129	Bordeaux		France
36	Mg0003 40360	Limoges		France
37	Mg0003 40426	Lyon		France
38	Mg0003 40130	Marseille		France
39	Mg0003 40132	Nice Cedex 1		France
40	Mg0003 40133	Paris		France
41	Mg0003 40131	Strasbourg		France
42	Mg0003 20160	Tbilisi		Georgia
43	Mg0003 20161	Tbilisi		Georgia
44	Mg0003 20163	Tbilisi		Georgia
45	Mg0003 20164	Tbilisi		Georgia
46	Mg0003 20165	Tbilisi		Georgia
47	Mg0003 40134	Essen		Germany
48	Mg0003 40135	Gummersbach		Germany
49	Mg0003 40140	Göttingen		Germany
50	Mg0003 40139	Jena		Germany
51	Mg0003 40078	Leipzig		Germany
52	Mg0003 40177	Münster		Germany
53	Mg0003 40082	Kistarcsa		Hungary
54	Mg0003 40178	Nyiregyhaza		Hungary
55	Mg0003 40283	Bologna		Italy
56	Mg0003 40144	Milano		Italy
57	Mg0003 40307	Napoli		Italy
58	Mg0003 40146	Pavia		Italy
59	Mg0003 40148	Roma		Italy
60	Mg0003 40150	Roma		Italy
61	Mg0003 20035	Bunkyō-Ku		Japan
62	Mg0003 20068	Chiba-Shi		Japan
63	Mg0003 20078	Hanamaki-Shi		Japan
64	Mg0003 20079	Hiroshima		Japan
65	Mg0003 20075	Kobe		Japan
66	Mg0003 20071	Nagasaki		Japan
67	Mg0003 20067	Sapporo		Japan
68	Mg0003 20077	Sendai		Japan
69	Mg0003 20070	Shinjuku-Ku		Japan
70	Mg0003 20076	Shinjuku-Ku		Japan
71	Mg0003 20032	Suita		Japan
72	Mg0003 40155	Gdańsk		Poland
73	Mg0003 40151	Lublin		Poland
74	Mg0003 40153	Poznań		Poland
75	Mg0003 40154	Łódź		Poland
76	Mg0003 20027	Moscow		Russian Federation
77	Mg0003 20169	Novosibirsk		Russian Federation
78	Mg0003 20001	Saint Petersburg		Russian Federation
79	Mg0003 20028	Saint Petersburg		Russian Federation
80	Mg0003 20055	Saint Petersburg		Russian Federation
81	Mg0003 40468	Belgrade		Serbia
82	Mg0003 40467	Niš		Serbia
83	Mg0003 40159	Barcelona		Spain
84	Mg0003 40160	Barcelona		Spain
85	Mg0003 40267	Barcelona		Spain
86	Mg0003 40157	Hospitalet de Llobregat		Spain
87	Mg0003 40350	Murcia		Spain
88	Mg0003 40308	San Sebastián De Los Reyes		Spain
89	Mg0003 20080	Taichung		Taiwan
90	Mg0003 20081	Taipei		Taiwan
91	Mg0003 20086	Taipei		Taiwan
92	Mg0003 40175	London		United Kingdom