An Extension Study of MOM-M281-004 to Evaluate the Safety, Tolerability, and Efficacy of M281 Administered to Patients With Generalized Myasthenia Gravis

NCT03896295 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: MOM-M281-0052018-003618-41
• Study Type: interventional
• Target: 37
• Locations: 8 countries
• Sites: 54

Brief Summary

The purpose of this study is to evaluate the long-term safety and tolerability of M281 in participants with generalized myasthenia gravis (gMG)

Conditions

Generalized Myasthenia Gravis

Keywords

M281; Generalized Myasthenia Gravis

Outcome Measures

Primary Outcomes (21)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Number of participants with TEAEs were reported. An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are defined as any AE occurring during or after the initiation of the first infusion of study drug in this study.

  Up to 257 days post-baseline (Baseline is Day 1)

• Number of Participants With Serious Adverse Events (SAEs)

  An adverse event (AE) is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. SAE is defined as any AE occurring at any dose that results in any of the following outcomes: death, life-threatening AE, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect.

  Up to 257 days post-baseline

• Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESIs)

  Number of participants with treatment-emergent AESIs were reported. Severe infections and hypoalbuminemia (Grade 3 or higher according to the Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) were considered as AESIs.

  Up to 257 days post-baseline

• Number of Participants With Treatment-emergent Abnormal Vital Signs

  Number of participants with treatment-emergent abnormal vital signs including pulse rate (less than or equal to \[\<=\] 50 beats per minutes \[bpm\] with greater than or equal to \[\>=\] 15 bpm decrease from baseline, \>= 120 bpm with \>=15 bpm increase from baseline), systolic blood pressure (SBP) (\<= 90 millimeters of mercury \[mmHg\] with \>= 20 mmHg decrease from baseline, \>= 160 mmHg with \>= 20 mmHg increase from baseline) and diastolic blood pressure (DBP) (\<= 50 mmHg with \>=15 mmHg decrease from baseline, \>=100 mmHg with \>=15 mmHg decrease from baseline) were reported.

  Up to 257 days post-baseline

• Number of Participants With Abnormalities in Physical Examinations

  Number of participants with abnormalities in physical examinations (abdomen, head, ears, eyes, nose, throat, and sinuses, lungs, neurological, skin, blood and lymphatic system, cardiovascular, chest, gastrointestinal, general appearance and musculoskeletal) were reported.

  Week 12

• Change From Baseline in Chemistry Laboratory Parameters: Albumin and Protein

  Change from baseline in chemistry laboratory parameters: albumin and protein were reported.

  Baseline up to Week 12

• Change From Baseline in Chemistry Laboratory Parameters: Bicarbonate, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglycerides, Urate and Urea Nitrogen

  Change from baseline in chemistry laboratory parameters: bicarbonate, calcium, chloride, cholesterol, glucose, phosphate, potassium, sodium, triglycerides, urate and urea nitrogen were reported.

  Baseline up to Week 12

• Change From Baseline in Chemistry Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase

  Change from baseline in chemistry laboratory parameters alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), creatine kinase, gamma glutamyl transferase, lactate dehydrogenase were reported.

  Baseline up to Week 12

• Change From Baseline in Chemistry Laboratory Parameters: Bilirubin, Creatinine and Direct Bilirubin

  Change from baseline in chemistry laboratory parameters: bilirubin, creatinine and direct bilirubin were reported.

  Baseline up to Week 12

• Change From Baseline in Hematology Laboratory Parameter: Erythrocytes (Red Blood Cell)

  Change from baseline in erythrocytes (red blood cells) (hematology laboratory parameter) was reported.

  Baseline up to Week 12

• Change From Baseline in Hematology Laboratory Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes

  Change from baseline in hematology laboratory parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes were reported.

  Baseline up to Week 12

• Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration

  Change from baseline in erythrocytes mean corpuscular hemoglobin (HGB) concentration (hematology laboratory parameter) were reported.

  Baseline up to Week 12

• Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (HGB)

  Change from baseline in erythrocytes mean corpuscular HGB (hematology laboratory parameter) was reported.

  Baseline up to Week 12

• Change From Baseline in Hematology Laboratory Parameter: Erythrocytes Mean Corpuscular Volume

  Change from baseline in erythrocytes mean corpuscular volume (hematology laboratory parameter) was reported.

  Baseline up to Week 12

• Change From Baseline in Hematology Laboratory Parameter: Hematocrit

  Change from baseline in hematocrit (hematology laboratory parameter) was reported.

  Baseline up to Week 12

• Change From Baseline in Hematology Laboratory Parameter: Hemoglobin

  Change from baseline in hemoglobin (hematology laboratory parameter) was reported.

  Baseline up to Week 12

• Change From Baseline in Urinalysis Laboratory Parameter: pH

  Change from baseline in pH (urinalysis laboratory parameter) was reported.

  Baseline up to Week 12

• Change From Baseline in Urinalysis Laboratory Parameter: Specific Gravity

  Change from baseline in specific gravity (urinalysis laboratory parameter) was reported.

  Baseline up to Week 12

• Number of Participants With Treatment-emergent Abnormal Electrocardiograms (ECG) Values

  Number of participants with treatment-emergent abnormal ECG values for variables including mean heart rate (abnormally low refers to less than or equal to \[\<=\] 50 beats per minute \[bpm\], abnormally high refers greater than or equal to \[\>=\] 120 bpm), PR interval (abnormally low refers to \< 120 and abnormally high refers to \>200 milliseconds \[msec\]), RR interval (abnormally low refers to \<600 msec and abnormally high refers to \>1200 msec) and QRS duration (abnormally \> 120) were reported.

  Up to 257 days post-baseline

• Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Scores

  Number of participants with C-SSRS scores were reported. C-SSRS is a clinician-administered questionnaire designed to solicit occurrence, severity, and frequency of suicide-related ideation and behaviors. Total score ranges from 1 to 10, score of 0 was assigned (0="no event that can be assessed based on C-SSRS"). Higher total scores indicate greater severity. Maximum score assigned for each participant was summarized into one of 3 categories: no suicidal ideation or behavior (0), suicidal ideation (1 to 5): higher score indicates more suicidal ideation, suicidal behavior (6 to 10): higher score indicates more suicidal behavior. Suicidal ideation includes participants who did not have suicidal ideation or behavior at baseline and had suicidal ideation without behavior at some time point post-baseline. Suicidal behavior includes participants who did not have suicidal ideation or behavior at baseline and had suicidal behavior at some time point post-baseline (baseline=Day 1).

  Up to 257 days post-baseline

• Number of Participants With Below/Above Normal Values of Coagulation Laboratory Parameter

  Number of participants with at least one value above upper limit of normal (\>ULN) or below the lower limit of normal (\< LLN) value of coagulation parameters (activated partial thromboplastin time \[APTT\] and prothrombin time \[PT\]) were reported. The lab reference range for APTT is 25.1 to 36.5 seconds. The lab reference range for PT is 9.4 to 12.5 seconds.

  Up to 257 days post-baseline

Secondary Outcomes (10)

• Change From Baseline in Total Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score Over Time

  Baseline up to Weeks 4, 8, 12, 24, End of treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline)

• Number of Participants With a 2-, 3-, 4-, 5-, 6-, 7-, or Greater Than or Equal to (>=) 8-point Improvement in Total MG-ADL Score Over Time

  Weeks 4, 8, 12, 24, End of treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline)

• Change From Baseline in Total Quantitative Myasthenia Gravis (QMG) Score Over Time

  Baseline up to Weeks 4, 8, 12, 24, End of Treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline)

• Change From Baseline in Total Revised Myasthenia Gravis Quality of Life - 15 Scale (MG-QoL15r) Score Over Time

  Baseline up to Weeks 4, 8, 12, 24, End of Treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline)

• Change From Baseline in Clinical Global Impression of Severity (CGI-S) Rating Score Over Time

  Baseline up to Weeks 4, 8, 12, 24, End of Treatment (EoT) (up to 253 days post-baseline), Follow-up (up to 257 days post-baseline)

Study Arms (1)

M281

EXPERIMENTAL

Drug: M281

Interventions

M281 DRUG

M281 injection administered as intravenous infusion

M281

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Participants must be ≥18 years of age with a documented history of Generalized Myasthenia Gravis (gMG) and clinical signs/symptoms of gMG, not pregnant or breastfeeding, previously participated in the MOM-281-004 study, had no major eligibility deviations or other major protocol deviations or not met any of the stopping criteria or discontinued study drug in the MOM-M281-004 study for any reason other than the need for rescue therapy as specified in the MOM-M281-004 study. Additional, more specific criteria are defined in the protocol.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Momenta Pharmaceuticals, Inc.: lead

Study Sites (54)

Momenta Investigational Site

Phoenix, Arizona, 85013, United States

Location

Momenta Investigational Site

Los Angeles, California, 90048, United States

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Momenta Investigational Site

Orange, California, 92868, United States

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Momenta Investigational Site

Stanford, California, 94305, United States

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Momenta Investigational Site

Aurora, Colorado, 80045, United States

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Momenta Investigational Site

New Haven, Connecticut, 06511, United States

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Momenta Investigational Site

Boca Raton, Florida, 33487, United States

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Momenta Investigational Site

Maitland, Florida, 32751, United States

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Momenta Investigational Site

Port Charlotte, Florida, 33952, United States

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Momenta Investigational Site

St. Petersburg, Florida, 33713, United States

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Momenta Investigational Site

Augusta, Georgia, 30912, United States

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Momenta Investigational Site

Fairway, Kansas, 66205, United States

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Momenta Investigational Site

Boston, Massachusetts, 02114, United States

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Momenta Investigational Site

Boston, Massachusetts, 02115, United States

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Momenta Investigational Site

Boston, Massachusetts, 02215, United States

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Momenta Investigational Site

New Brunswick, New Jersey, 08550, United States

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Momenta Investigational Site

New York, New York, 10021, United States

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Momenta Investigational Site

Charlotte, North Carolina, 28207, United States

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Momenta Investigational Site

Durham, North Carolina, 27710, United States

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Momenta Investigational Site

Raleigh, North Carolina, 27607, United States

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Momenta Investigational Site

Cincinnati, Ohio, 45267, United States

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Momenta Investigational Site

Columbus, Ohio, 43210, United States

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Momenta Investigational Site

Cordova, Tennessee, 38106, United States

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Momenta Investigational Site

Austin, Texas, 78756, United States

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Momenta Investigational Site

Round Rock, Texas, 78681, United States

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Momenta Investigational Site

Leuven, Vlaams Brabant, 3000, Belgium

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Momenta Investigational Site

Antwerp, 2650, Belgium

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Momenta Investigational Site

Brussels, 1070, Belgium

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Momenta Investigational Site

Edmonton, Alberta, T6G 2G3, Canada

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Momenta Investigational Site

London, Ontario, N6A 5A5, Canada

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Momenta Investigational Site

Toronto, Ontario, M5G 2C4, Canada

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Momenta Investigational Site

Québec, Quebec, G1J 1Z4, Canada

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Momenta Investigational Site

Göttingen, Lower Saxony, 37075, Germany

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Momenta Investigational Site

Düsseldorf, 40225, Germany

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Momenta Investigational Site

Gummersbach, 51643, Germany

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Momenta Investigational Site

Münster, 48149, Germany

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Momenta Investigational Site

Cefalù, 90015, Italy

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Momenta Investigational Site

Messina, 98125, Italy

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Momenta Investigational Site

Milan, 20133, Italy

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Momenta Investigational Site

Krakow, 31-505, Poland

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Momenta Investigational Site

Lodz, 90-324, Poland

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Momenta Investigational Site

Warsaw, 01-684, Poland

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Momenta Investigational Site

Warsaw, 01-868, Poland

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Momenta Investigational Site

Barcelona, Catalan, 08035, Spain

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Momenta Investigational Site

Barcelona, Catalan, 08041, Spain

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Momenta Investigational Site

Barcelona, Catalonia, 08036, Spain

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Momenta Investigational Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Momenta Investigational Site

Donostia / San Sebastian, Gipuzkoa, 20014, Spain

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Momenta Investigational Site

Madrid, 28007, Spain

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Momenta Investigational Site

Madrid, 28040, Spain

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Momenta Investigational Site

Seville, 41013, Spain

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Momenta Investigational Site

Valencia, 46026, Spain

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Momenta Investigational Site

Birmingham, B15 2TH, United Kingdom

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Momenta Investigational Site

Sheffield, S11 9NE, United Kingdom

Location

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Study was originally halted due to the COVID-19 pandemic. The study was later terminated prematurely due to the continuing COVID-19 pandemic, and because the participants will have the option to enter into an open-label extension portion of a planned future study. It was not due to safety concerns.

Results Point of Contact

• Title: DIRECTOR CLINICAL RESEARCH
• Organization: Momenta Pharmaceuticals, Inc.

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: March 29, 2019
• Study Start: August 6, 2019
• Primary Completion: December 9, 2020
• Study Completion: December 9, 2020
• Last Updated: June 27, 2023
• Results First Posted: February 16, 2022

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); DE (4); IT (3); BE (3); CA (4); PL (4); ES (9); US (25)