A Study of Nipocalimab in Children Aged 2 to Less Than 18 Years With Generalized Myasthenia Gravis

• ClinicalTrials.gov Identifier: NCT05265273
• Recruitment Status: Recruiting
• First Posted: March 3, 2022
• Last Update Posted: May 31, 2023
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

The purpose of this study is to determine the effect of nipocalimab on total serum immunoglobulin G (IgG) in pediatric participants 2 to less than (<) 18 years of age, the safety and tolerability of treatment with nipocalimab in children and adolescents and to evaluate the pharmacokinetics (PK) of nipocalimab in children and adolescents with generalized myasthenia gravis (gMG) who have an insufficient clinical response to ongoing, stable standard-of-care therapy.

Condition or disease	Intervention/treatment	Phase
Myasthenia Gravis	Drug: Nipocalimab	Phase 2; Phase 3

Expanded Access : An investigational treatment associated with this study is temporarily not available outside the clinical trial.   More info ...

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Uncontrolled Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Activity of Nipocalimab in Children Aged 2 to Less Than 18 Years With Generalized Myasthenia Gravis
• Actual Study Start Date: July 20, 2022
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nipocalimab; Participants aged 2 to less than [<] 18 years of age will receive nipocalimab once every two weeks for 24 weeks. After Week 24, all participants will have the option to enroll in long term extension (LTE).	Drug: Nipocalimab; Nipocalimab will be administered as an IV infusion.; Other Name: M281/JNJ-80202135

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in Total Serum Immunoglobulin-G (IgG) Antibodies Levels [ Time Frame: Up to 3 years ]
   Change from baseline in total serum IgG antibodies levels were reported.
2. Number of Participants with Infectious Adverse Events (AEs) [ Time Frame: Up to 3 years ]
   Number of participants with infectious AEs will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
3. Number of Participants with Serious AEs (SAEs) [ Time Frame: Up to 3 years ]
   Number of participants with SAEs will be reported. A SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important to prevent one of the outcomes listed above.
4. Number of Participants with Adverse Events of Special Interests (AESIs) [ Time Frame: Up to 3 years ]
   Number of participants with AESIs will be reported. Treatment-emergent AEs associated with the following situations are considered an AESI: a) infections that are severe or require intravenous (IV) anti-infective or operative/invasive intervention; b) hypoalbuminemia with albumin less than (<)20 grams per liter (g/L) [<] 2.0 grams per deciliter [g/dL]) and c) opportunistic infections. Any AE occurring at or after the initial administration of study intervention through end of study is treatment emergent.
5. Number of Participants with Abnormalities in Clinical Laboratory Tests [ Time Frame: Up to 3 years ]
   Number of participants with abnormalities in clinical laboratory tests (including chemistry, hematology, coagulation, and urinalysis) will be reported.
6. Number of Participants with Abnormalities in Vital Signs [ Time Frame: Up to 3 years ]
   Number of participants with abnormalities in vital signs including sitting pulse/heart rate, sitting systolic and diastolic blood pressure, and oral temperature (degrees Celsius) will be reported.
7. Number of Participants with Abnormalities in Physical Examination [ Time Frame: Up to 3 years ]
   Number of participants with abnormalities in physical examinations including height, weight, assessments of the skin, head, eyes, ears, nose, throat, neck, thyroid, lungs, heart, abdomen, lymph nodes and extremities will be reported.
8. Serum Concentration of Nipocalimab over Time [ Time Frame: Up to 3 years ]
   Serum samples will be analyzed to determine concentrations of nipocalimab using a validated, specific, and sensitive immunoassay method.
9. Clearance (CL) of Nipocalimab [ Time Frame: Up to 3 years ]
   CL is defined as the volume of serum from which nipocalimab is completely removed per unit time.
10. Volume of Distribution (V) of Nipocalimab [ Time Frame: Up to 3 years ]
    V is defined as the representation of nipocalimab's propensity to either remain in the serum or redistribute to other tissue compartments.
11. Half-life (t1/2) of Nipocalimab [ Time Frame: Up to 3 years ]
    t1/2 is defined as the time it takes for nipocalimab's active substance in the body to reduce by half.
12. Steady-state Peak Concentration (Cpeak,ss) of Nipocalimab [ Time Frame: Up to 3 years ]
    Cpeak,ss is defined as the peak serum concentration of nipocalimab at steady state.
13. Steady-state Trough concentration (Ctrough,ss) of Nipocalimab [ Time Frame: Up to 3 years ]
    Ctrough,ss will be reported. It is defined as the observed serum concentration of nipocalimab just prior to the beginning of a dosing interval at steady state.
14. Steady-state Area Under the Curve (AUCss) of Nipocalimab [ Time Frame: Up to 3 years ]
    AUCss is defined as the area under the curve for nipocalimab at steady state.

Secondary Outcome Measures :

1. Change from Baseline in Myasthenia Gravis -Activities of Daily Living (MG-ADL) Score [ Time Frame: Up to 3 years ]
   Change from baseline in MG-ADL score will be reported. The MG-ADL score provides a rapid assessment of the participant's myasthenia gravis (MG) symptom severity. Eight functions (talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, double vision, eyelid droop) are rated on a 4-point scale: 0 (no impairment) to 3 (severe impairment). The total score will be sum of eight function scores and can range from 0 to 24. A higher score indicates greater symptom severity.
2. Change in the Quantitative Myasthenia Gravis (QMG) Score [ Time Frame: Up to 3 years ]
   The QMG score is a standardized quantitative strength assessment comprising 13 components (and is administered by a trained qualified healthcare professional [HCP] eg, physician, physician assistant, nurse practitioner, nurse). The quantitative results of each strength component are mapped to the following 4-point scale: 0 equals to (=) none, 1 = mild, 2 = moderate and 3 = severe. The total score will be sum of 13 components scores and can range from 0 to 39. A higher score indicates greater weakness.
3. European Quality of Life 5-Dimension Youth (EQ-5D-Y) Tool Score [ Time Frame: Up to 3 years ]
   The EQ-5D-Y is a standardized child friendly instrument for use as a measure of health status, primarily designed for self-completion by children and adolescents, or via a proxy version to be completed by the child's caregiver. The EQ-5D-Y descriptive system comprises the following 5 dimensions: Mobility, looking after myself (washing and dressing), usual activities, pain or discomfort and feeling worried or unhappy. Each of the 5 dimensions is divided into 3 levels of perceived problems (Level 1 indicating no problem, Level 2 indicating some problems, Level 3 a lot of problems).
4. Neurological Quality of Life (Neuro-QoL) Pediatric Fatigue Score [ Time Frame: Up to 3 years ]
   The Neuro-QoL pediatric fatigue score will be used to assess the impact of fatigue in participants aged 10 to less than (<) 18 years. The participant will rate each of the 11 items on a 5-point scale. Higher scores indicate greater fatigue.
5. Patient Global Impression of Severity (PGI-S) Score [ Time Frame: Up to 3 years ]
   The PGI-S score will be used to assess the severity of fatigue due to generalized myasthenia gravis (gMG) in participants aged 10 to < 18 years. Participants will be asked to rate their fatigue over the past 7 days using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe. Higher scores indicate greater severity of fatigue.
6. Patient Global Impression of Change (PGI-C) Score [ Time Frame: Up to 3 years ]
   The PGI-C score will be used to assess if there has been an improvement or decline in patient-reported fatigue since the beginning of the treatment in participants aged 10 to <18 years. Participants will be asked to rate their current fatigue as compared to when they started the study, using the following 7-point scale: 1 = Much better, 2 = Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately worse, and 7 = Much worse. Higher scores indicate greater change in overall fatigue.
7. Number of Participants with Anti-Drug Antibodies [ADAs] to Nipocalimab [ Time Frame: Up to 3 years ]
   Number of participants with ADAs to nipocalimab will be reported.
8. Number of Participants with Neutralizing Antibodies (NAbs) to Nipocalimab [ Time Frame: Up to 3 years ]
   Number of participants with NAbs to nipocalimab will be reported.
9. Number of Participants with Vaccine Antibody Titers to Diphtheria or Tetanus [ Time Frame: Up to 3 years ]
   Number of participants with vaccine antibody titers to diphtheria or tetanus will be reported.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of myasthenia gravis (MG) with generalized muscle weakness meeting the clinical criteria for generalized myasthenia gravis (gMG) as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class IIa/b, IIIa/b, or IVa/b at screening
• Has a positive serologic test for acetylcholine receptor (anti-AChR) antibodies or muscle-specific tyrosine kinase (anti-MuSK) antibodies at screening
• A participant using herbal, naturopathic, traditional Chinese remedies, ayurvedic or nutritional supplements, or medical marijuana (with a doctor's prescription) is eligible if the use of these medications is acceptable to the Investigator. These remedies must remain at a stable dose and regimen throughout the study
• Has sufficient venous access to allow drug administration by infusion and blood sampling as per the protocol
• Participants should have a body weight and body mass index between 5th and 95th percentile for age and sex. Obese participants greater than 95th percentile and underweight participants below 5th percentile may participate following medical clearance
• A female of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at Screening and a negative urine pregnancy test at Day 1 prior to administration of study intervention

Exclusion Criteria:

• Has a history of severe and/or uncontrolled hepatic (example, viral/alcoholic/ autoimmune hepatitis/ cirrhosis/ and/or metabolic liver disease), gastrointestinal, renal, pulmonary, cardiovascular (including congenital heart diseases), psychiatric, neurological musculoskeletal disorder, any other medical disorder(s) (example, diabetes mellitus), or clinically significant abnormalities in screening laboratory, that might interfere with participant's full participation in the study, and/ or might jeopardize the safety of the participant or the validity of the study results
• Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her generalized myasthenia gravis (gMG), or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant
• Has had a thymectomy within 12 months prior to screening, or thymectomy is planned during the Active treatment Phase of the study
• Has shown a previous severe immediate hypersensitivity reaction, such as anaphylaxis to therapeutic proteins (example, monoclonal antibodies)
• Has experienced myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks of screening

Contacts and Locations

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

Locations

United States, Arizona

Phoenix Children's Hospital; Recruiting

Phoenix, Arizona, United States, 85016

United States, California

Lucile Packard Children's Hospital Stanford; Recruiting

Palo Alto, California, United States, 94304

UCSF Benioff Children's Hospital; Recruiting

San Francisco, California, United States, 94158

United States, Colorado

Children's Hospital Colorado; Recruiting

Aurora, Colorado, United States, 80045

United States, Florida

University of South Florida Morsani Center for Advanced Healthcare; Recruiting

Tampa, Florida, United States, 33613

United States, Kansas

University of Kansas Medical Center; Recruiting

Lawrence, Kansas, United States, 66045

United States, Michigan

C.S. Mott Children's Hospital; Recruiting

Ann Arbor, Michigan, United States, 48109

United States, Pennsylvania

Childrens Hospital Of Philadelphia; Recruiting

Philadelphia, Pennsylvania, United States, 19106

Japan

Nagano Children's Hospital; Recruiting

Azumino-shi, Nagano, Japan, 399-8288

Chiba University Hospital; Recruiting

Chiba, Japan, 260-8677

University of Miyazaki Hospital; Recruiting

Miyazaki, Japan, 889-1692

Saitama Prefecture Children's Medical Center; Recruiting

Saitama-shi, Japan, 330-8777

Tokyo Women's Medical University Hospital; Recruiting

Shinjuku-ku, Japan, 162-8666

Netherlands

Leiden University Medical Center; Recruiting

Leiden, Netherlands, 2333 ZA

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT05265273
• Other Study ID Numbers: CR109137; 2021-002479-20 ( EudraCT Number ); 80202135MYG2001 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: March 3, 2022
• Last Update Posted: May 31, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:

Pediatric

Additional relevant MeSH terms:

Myasthenia Gravis; Muscle Weakness; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases