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
A Study of Nipocalimab in Children Aged 2 to less than 18 Years with Generalized Myasthenia Gravis
Tominaga Yushin
Janssen Pharmaceutical K.K.
5-2, Nishi-kanda 3-chome, Chiyoda-ku, Tokyo
+81-120-183-275
DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com
Medical Information Center
Janssen Pharmaceutical K.K.
5-2, Nishi-kanda 3-chome, Chiyoda-ku, Tokyo
+81-120-183-275
DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com
Recruiting
Oct. 28, 2022
Aug. 17, 2022
12
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
- Age: For US sites only: 8 to <18 years
- 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
- 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 or musculoskeletal disorder or 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
2age old over
17age old under
Both
Myasthenia Gravis
Experimental: Nipocalimab
Participants age 2 to less than (<) 18 years of age (globally) and 8 to <18 years of age (for US sites only) will be divided into 2 cohorts as per their ageadolescents 12 to <18 years and children 2 to <12 years and 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 Names: M281/JNJ-80202135
1. Change from Baseline in Total Serum Immunoglobulin-G (IgG) Levels
Change from baseline in total serum IgG levels were reported.
[Time Frame: Up to 3 years]
2. Number of Participants with Infectious Adverse Events (AEs)
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.
[Time Frame: Up to 3 years]
3. Number of Participants with Serious AEs (SAEs)
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.
[Time Frame: Up to 3 years]
4. Number of Participants with Adverse Events of Special Interests (AESIs)
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]) c)
opportunistic infections and d) Serious and non-serious deep-vein thrombosis (DVT) and/or pulmonary embolism (PE). Any AE occurring at or after the initial administration of study intervention through end of study is treatment emergent.
[Time Frame: Up to 3 years]
5. Number of Participants with Abnormalities in Clinical Laboratory Tests
Number of participants with abnormalities in clinical laboratory tests (including chemistry, hematology, coagulation, and urinalysis) will be reported.
[Time Frame: Up to 3 years]
6. Number of Participants with Abnormalities in Vital Signs
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.
[Time Frame: Up to 3 years]
7. Number of Participants with Abnormalities in Physical Examination
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.
[Time Frame: Up to 3 years]
8. Serum Concentration of Nipocalimab over Time
Serum samples will be analyzed to determine concentrations of nipocalimab using a validated, specific, and sensitive immunoassay method.
[Time Frame: Up to 3 years]
9. Clearance (CL) of Nipocalimab
CL is defined as the volume of serum from which nipocalimab is completely removed per unit time.
[Time Frame: Up to 3 years]
10. Volume of Distribution (V) of Nipocalimab
V is defined as the representation of nipocalimab's propensity to either remain in the serum or redistribute to other tissue compartments.
[Time Frame: Up to 3 years]
11. Half-life (t1/2) of Nipocalimab
t1/2 is defined as the time it takes for nipocalimab's active substance in the body to reduce by half.
[Time Frame: Up to 3 years]
12. Steady-state Peak Concentration (Cpeak,ss) of Nipocalimab
Cpeak,ss is defined as the peak serum concentration of nipocalimab at steady state.
[Time Frame: Up to 3 years]
13. Steady-state Trough concentration (Ctrough,ss) of Nipocalimab
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.
[Time Frame: Up to 3 years]
14. Steady-state Area Under the Curve (AUCss) of Nipocalimab
AUCss is defined as the area under the curve for nipocalimab at steady state.
[Time Frame: Up to 3 years]
15. Change from Baseline in Myasthenia Gravis -Activities of Daily Living (MG-ADL) Score
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.
[Time Frame: Up to 3 years]
16. Change in the Quantitative Myasthenia Gravis (QMG) Score
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.
[Time Frame: Up to 3 years]
17. European Quality of Life 5-Dimension Youth (EQ-5D-Y) Tool Score
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).
[Time Frame: Up to 3 years]
18. Neurological Quality of Life (Neuro-QoL) Pediatric Fatigue Score
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.
[Time Frame: Up to 3 years]
19. Patient Global Impression of Severity (PGI-S) Score
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.
[Time Frame: Up to 3 years]
20. Patient Global Impression of Change (PGI-C) Score
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.
[Time Frame: Up to 3 years]
21. Number of Participants with Anti-Drug Antibodies [ADAs] to Nipocalimab
Number of participants with ADAs to nipocalimab will be reported.
[Time Frame: Up to 3 years]
22. Number of Participants with Neutralizing Antibodies (NAbs) to Nipocalimab
Number of participants with NAbs to nipocalimab will be reported.
[Time Frame: Up to 3 years]
23. Number of Participants with Vaccine Antibody Titers to Diphtheria or Tetanus
Number of participants with vaccine antibody titers to diphtheria or tetanus will be reported.
[Time Frame: Up to 3 years]
Janssen Pharmaceutical K.K.
Chiba University Hospital Institutional Review Board
1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba
Approval
April. 11, 2022
Yes
The data sharing policy of Johnson & Johnson Innovative Medicine is available at www.innovativemedicine.jnj.com/our-innovation/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
