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

Generalized Myasthenia Gravis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03971422
• Other study ID #: MG0003
• Secondary ID: 2019-000968-18
• Status: Completed
• Phase: Phase 3
• Start date: June 3, 2019
• Est. completion date: October 26, 2021

Study information

• Verified date: August 2023
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: October 26, 2021
• Est. primary completion date: August 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Generalized Myasthenia Gravis
• Muscle Weakness
• Myasthenia Gravis

Intervention

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

Other:
• Placebo
Subjects will receive placebo at pre-specified time points.

Locations

Country	Name	City	State
Belgium	Mg0003 40121	Bruxelles
Canada	Mg0003 50067	Calgary
Canada	Mg0003 50066	Montréal
Canada	Mg0003 50070	Québec
Canada	Mg0003 50069	Toronto
Czechia	Mg0003 40125	Ostrava
Czechia	Mg0003 40124	Praha 2
Denmark	Mg0003 40128	Aalborg
Denmark	Mg0003 40127	Aarhus n
Denmark	Mg0003 40126	Copenhagen
Denmark	Mg0003 40489	Odense
France	Mg0003 40129	Bordeaux
France	Mg0003 40070	Clermont-Ferrand
France	Mg0003 40512	Garches
France	Mg0003 40510	Le Kremlin-Bicêtre
France	Mg0003 40360	Limoges
France	Mg0003 40426	Lyon
France	Mg0003 40130	Marseille
France	Mg0003 40017	Nantes
France	Mg0003 40132	Nice Cedex 1
France	Mg0003 40133	Paris
France	Mg0003 40131	Strasbourg
Georgia	Mg0003 20160	Tbilisi
Georgia	Mg0003 20161	Tbilisi
Georgia	Mg0003 20163	Tbilisi
Georgia	Mg0003 20165	Tbilisi
Germany	Mg0003 40134	Essen
Germany	Mg0003 40140	Göttingen
Germany	Mg0003 40135	Gummersbach
Germany	Mg0003 40139	Jena
Germany	Mg0003 40078	Leipzig
Germany	Mg0003 40177	Münster
Hungary	Mg0003 40082	Kistarcsa
Hungary	Mg0003 40178	Nyiregyhaza
Italy	Mg0003 40283	Bologna
Italy	Mg0003 40149	Lazio
Italy	Mg0003 40144	Milano
Italy	Mg0003 40307	Napoli
Italy	Mg0003 40146	Pavia
Italy	Mg0003 40148	Roma
Italy	Mg0003 40150	Roma
Japan	Mg0003 20035	Bunkyo-Ku
Japan	Mg0003 20068	Chiba-Shi
Japan	Mg0003 20078	Hanamaki-Shi
Japan	Mg0003 20079	Hiroshima
Japan	Mg0003 20075	Kobe
Japan	Mg0003 20071	Nagasaki
Japan	Mg0003 20074	Osaka-sayama
Japan	Mg0003 20067	Sapporo
Japan	Mg0003 20077	Sendai
Japan	Mg0003 20070	Shinjuku-Ku
Japan	Mg0003 20076	Shinjuku-Ku
Japan	Mg0003 20032	Suita
Poland	Mg0003 40155	Gdansk
Poland	Mg0003 40154	Lódz
Poland	Mg0003 40151	Lublin
Poland	Mg0003 40153	Poznan
Russian Federation	Mg0003 20168	Krasnoyarsk
Russian Federation	Mg0003 20027	Moscow
Russian Federation	Mg0003 20169	Novosibirsk
Russian Federation	Mg0003 20001	Saint Petersburg
Russian Federation	Mg0003 20028	Saint Petersburg
Russian Federation	Mg0003 20029	Saint Petersburg
Russian Federation	Mg0003 20055	Saint Petersburg
Russian Federation	Mg0003 20197	Samara
Serbia	Mg0003 40468	Belgrade
Serbia	Mg0003 40467	Niš
Spain	Mg0003 40159	Barcelona
Spain	Mg0003 40160	Barcelona
Spain	Mg0003 40267	Barcelona
Spain	Mg0003 40157	Hospitalet de Llobregat
Spain	Mg0003 40161	Madrid
Spain	Mg0003 40162	Madrid
Spain	Mg0003 40341	Málaga
Spain	Mg0003 40350	Murcia
Spain	Mg0003 40308	San Sebastián De Los Reyes
Taiwan	Mg0003 20080	Taichung
Taiwan	Mg0003 20081	Taipei
Taiwan	Mg0003 20086	Taipei
Taiwan	Mg0003 20082	Taoyuan
United Kingdom	Mg0003 40175	London
United Kingdom	Mg0003 40168	Nottingham
United States	Mg0003 50110	Ann Arbor	Michigan
United States	Mg0003 50075	Augusta	Georgia
United States	Mg0003 50101	Aurora	Colorado
United States	Mg0003 50084	Charleston	South Carolina
United States	Mg0003 50086	Charlotte	North Carolina
United States	Mg0003 50117	Charlotte	North Carolina
United States	Mg0003 50109	Chicago	Illinois
United States	Mg0003 50076	Columbus	Ohio
United States	Mg0003 50102	Detroit	Michigan
United States	Mg0003 50074	Fairway	Kansas
United States	Mg0003 50323	Honolulu	Hawaii
United States	Mg0003 50113	Houston	Texas
United States	Mg0003 50114	Indianapolis	Indiana
United States	Mg0003 50121	Lexington	Kentucky
United States	Mg0003 50072	Los Angeles	California
United States	Mg0003 50120	Miami	Florida
United States	Mg0003 50122	Miami	Florida
United States	Mg0003 50077	New York	New York
United States	Mg0003 50092	Orange	California
United States	Mg0003 50089	Philadelphia	Pennsylvania
United States	Mg0003 50096	Philadelphia	Pennsylvania
United States	Mg0003 50081	Phoenix	Arizona
United States	Mg0003 50104	Rochester	Minnesota
United States	Mg0003 50105	Saint Louis	Missouri
United States	Mg0003 50097	San Francisco	California
United States	Mg0003 50099	San Francisco	California
United States	Mg0003 50082	Scottsdale	Arizona
United States	Mg0003 50073	Tampa	Florida
United States	Mg0003 50088	Washington	District of Columbia
United States	Mg0003 50090	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  Denmark,  France,  Georgia,  Germany,  Hungary,  Italy,  Japan,  Poland,  Russian Federation,  Serbia,  Spain,  Taiwan,  United Kingdom, 

References & Publications (1)

Bril V, Druzdz A, Grosskreutz J, Habib AA, Mantegazza R, Sacconi S, Utsugisawa K, Vissing J, Vu T, Boehnlein M, Bozorg A, Gayfieva M, Greve B, Woltering F, Kaminski HJ; MG0003 study team. Safety and efficacy of rozanolixizumab in patients with generalised — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Day 43 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score	The Myasthenia Gravis Activities of Daily Living (MG-ADL) is an 8-item patient-reported outcome (PRO) instrument developed on the basis of the Quantitative Myasthenia Gravis (QMG). The MG-ADL targeted symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The total MG-ADL score was obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3), where 0 represents no symptoms or impaired performance and 3 represents the most severe symptoms or impaired performance. The total score ranges from 0 to 24, with a higher score indicating more disability. A positive change in the score indicates worsening and a negative change indicates improvement.	Baseline and Day 43
Secondary	Percentage of Participants Achieving Myasthenia Gravis-Activities of Daily Living (MG-ADL) Response at Day 43	The MG-ADL is an 8-item PRO instrument developed on the basis of the QMG. The MG-ADL targeted symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The total MG-ADL score was obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3), where 0 represents no symptoms or impaired performance and 3 represents the most severe symptoms or impaired performance. The total score ranges from 0 to 24, with a higher score indicating more disability. A positive change in the score indicates worsening and a negative change indicates improvement. Study participants were classified as responders at Day 43 if the value was at least a 2-point improvement (decrease) from Baseline at Day 43.	Day 43
Secondary	Change From Baseline to Day 43 in Myasthenia Gravis-Composite (MG-C) Total Score	MG-C scale is a validated assessment and scale tests 10 items with individual item being weighted differently. The items included ptosis/upward gaze (range: 0 [>45 second] - 3 [Immediate]), double vision on lateral gaze (range: 0 [>45 second] - 4 [Immediate]), eye closure (range: 0 [Normal] - 2 [severe weakness]), talking (range: 0 [Normal] - 6 [difficult to understand speech]), chewing (range: 0 [Normal] - 6 [gastric tube]), swallowing (range: 0 [Normal] - 6 [gastric tube]), breathing (range: 0 [Normal] - 9 [ventilator dependence]), neck flexion (range: 0 [Normal] - 4 [severe weakness]), shoulder abduction (range: 0 [Normal] - 5 [severe weakness]) and hip flexion (range: 0 [Normal] - 5 [severe weakness]), lower scores= lower disease activity. Total MG-C score was obtained by summing responses to each individual item and score ranges from 0 to 50, with lower scores indicating lower disease activity. A positive change indicates worsening and a negative change indicates improvement.	Baseline and Day 43
Secondary	Change From Baseline to Day 43 in Quantitative Myasthenia Gravis (QMG) Total Score	The QMG is a validated assessment and the scale tested 13 items, including ocular and facial involvement, swallowing, speech, limb strength, and forced vital capacity. 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) and the score ranges from 0 to 39, with lower scores indicating lower disease activity. A positive change in the score indicates worsening and a negative change indicates improvement.	Baseline and Day 43
Secondary	Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Muscle Weakness Fatigability' Score	MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose response option that how frequently they experienced muscle weakness fatigability (items 34-42) over the past 7 days using a 5-point Likert scale (1="none of the time" to 5="all of the time") for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.	Baseline and Day 43
Secondary	Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Physical Fatigue' Score	The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose the response option that how frequently they experienced physical fatigue (items 19-33) over the past 7 days using a 5-point Likert scale (1="none of the time" to 5="all of the time") for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.	Baseline and Day 43
Secondary	Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Bulbar Symptoms' Score	The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose response option that best described severity of bulbar muscle weakness (items 6-15) symptoms over past 7 days using a 4-point Likert scale (1="none" to 4="severe") for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.	Baseline and Day 43
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	A TEAE is defined as an AE starting on or after the time of first administration of investigational medicinal product (IMP) up to and including 8 weeks after the last dose.	From Baseline until End of Study Visit (up to Week 14)
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal of Investigational Medicinal Product (IMP)	A TEAE is defined as an AE starting on or after the time of first administration of IMP up to and including 8 weeks after the last dose.	From Baseline until End of Study Visit (up to Week 14)