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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

21 Oct 2022 → ongoing

Decision date (initial)

2023-07-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Janssen Research & Development, LLC

External identifiers

EU CT number

2022-502539-21-00

EudraCT number

2021-002479-20

ClinicalTrials.gov

NCT05265273

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Pharmacodynamic

To evaluate the efficacy, safety, tolerability, and pharmacokinetics of nipocalimab in children and adolescents (2 to 17) with gMG who have an insufficient clinical response to ongoing, stable standard-of-care therapy

Conditions and MedDRA coding

Myasthenia gravis (MG)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002559-PIP02-19

Plan to share IPD

Yes

IPD 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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 2 to <18 years of age.
2. Diagnosis of MG with generalized muscle weakness meeting the clinical criteria for gMG as defined by the MGFA Clinical Classification Class IIa/b, IIIa/b, or IVa/b at screening
3. Has a positive serologic test for acetylcholine receptor (anti-AChR) antibodies or muscle-specific tyrosine kinase (anti-MuSK) antibodies at screening.
4. Has suboptimal response to current stable therapy(as defined in the protocol) for gMG according to the investigator.
5. Participants who have undergone splenectomy (if local regulatory authority has not requested exclusion of participants with splenectomy) must be at least 3 months post resection prior to screening and must be vaccinated as per the United States Center for Disease Control and Prevention annual Recommended Immunization Schedule for ages 18 years or younger, United States OR must be vaccinated as per country/territory-specific guidelines or local regulations. Note: This criterion is not applicable if splenectomy is excluded by the local authority.
6. Is recommended to be up to date on all age-appropriate vaccinations (eg diphtheria and tetanus) prior to screening as per routine local medical guidelines. It is strongly recommended that participants, as applicable, will have completed a locally approved (or emergency useauthorized) COVID-19 vaccination regimen and it should be at least 2 weeks prior to study related visits or procedures. Study participants should follow applicable local vaccine labeling, guidelines, and standards-of-care for patients receiving immune-targeted therapy when determining an appropriate interval between vaccination and study enrollment
7. A female of childbearing potential must have a negative highly sensitive serum at Screening and a negative urine pregnancy test at Day 1 prior to administration of study intervention.
8. Additional Inclusion criteria are included in the protocol

Exclusion criteria 21

1. Has a history of severe and/or uncontrolled hepatic (eg, 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) (eg, diabetes mellitus), risk factors for thrombosis events (eg, a history of VTE or antiphospholipid syndrome, or a personal or family history of heritable coagulation disorder such as Factor V Leiden, Protein S or Protein C deficiency, atrial fibrillation/flutter, major orthopedic surgery or significant trauma that may increase the risk of VTE, is expected to be immobilized for prolonged periods of time), or has 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.
2. Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her gMG, or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant. (Note: Participants should not be actively deteriorating at the screening or baseline visit such that they meet the criteria for Clinical Deterioration)
3. Has MGFA Class I disease or presence of MG crisis (MGFA Class V) at screening, history of MG crisis within 1 month of screening, or fixed weakness (and/or 'burnt out' MG).
4. Is dependent on gastric tube for nutritional needs or is ventilator dependent.
5. Is actively undergoing radiation or chemotherapy for an unresected thymoma/malignant thymoma. Participants with stable, benign thymoma (stage I or IIa, for example) for which no treatment has been undertaken in the past 3 years may be allowed following discussion with the sponsor's medical monitor.
6. Has had a thymectomy within 12 months prior to screening, or thymectomy is planned during the Active treatment Phase of the study.
7. Has current or a history of any neurologic disorder other than MG that might interfere with the accuracy of study assessments, including but not limited to any chronic neurodegenerative disease, altered level of consciousness, dementia, abnormal mental status, major congenital neurologic defect, Lambert-Eaton myasthenic syndrome, drug induced MG, or hereditary forms of myasthenia syndrome.
8. Currently has a malignancy or has a history of malignancy within 3 years before screening (with the exception of localized basal cell carcinoma and/or squamous cell carcinoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months [defined as a minimum of 12 weeks] before the first study intervention administration or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study intervention administration).
9. Has known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients (refer to the IB).
10. Has shown a previous severe immediate hypersensitivity reaction, such as anaphylaxis to therapeutic proteins (eg, monoclonal antibodies).
11. Has experienced myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks of screening
12. History of moderate or severe substance or alcohol use disorder according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) criteria, except nicotine or caffeine, within 1 year before Screening.
13. Is currently taking eculizumab or other novel immune agents, IgG Fcrelated protein therapeutics, or Fc- conjugated therapeutic agents, including factor or enzyme replacement.
14. Has received, rituximab within 6 months prior to first administration of study intervention.
15. Has received or is expected to receive a live vaccine within 4 weeks prior to screening or has a known need to receive a live vaccine during the study, or within 8 weeks after the last administration of study intervention. For the Bacille Calmette-Guerin (BCG) vaccine, see exclusion criterion 33. Participants are allowed to receive a vaccine conditionally approved by their regional health advisory for emergency use for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), unless it is a live vaccine. Concomitant enrollment in an investigational trial for any SARS-CoV-2 (COVID-19) vaccine while participating in this study is not permitted.
16. Has received plasmapheresis, immunoadsorption therapy, or IVIg within 4 weeks prior to baseline.
17. Has another medical condition that requires oral or parenteral corticosteroids unless the dose has been stable for at least 4 weeks prior to baseline and is expected to remain stable during the study. Inhaled, intra-articular, topical or ocular corticosteroids are not exclusionary.
18. Has another medical condition that requires an immunosuppressive agent unless the medication has been used for at least 6 months, the dose has been stable for at least 3 months prior to baseline and the medication and the dose are expected to remain stable during the study.
19. Has previously received nipocalimab.
20. Has had a BCG vaccination within 1 year of first administration of study intervention.
21. Additional Exclusion criteria are included in the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. The effect of nipocalimab on total serum IgG in pediatric participants 2 to <18 years of age with gMG who have an insufficient clinical response to ongoing, stable standard-of-care therapy.
2. The safety and tolerability of treatment with nipocalimab in pediatric participants 2 to <18 years of age with gMG who have an insufficient clinical response to ongoing, stable standardof- care therapy.
3. The pharmacokinetics of nipocalimab in pediatric participants 2 to <18 years of age with gMG who have an insufficient clinical response to ongoing, stable standard of care therapy.
4. All primary PK and IgG endpoints will be summarized descriptively over time for the evaluable population, and for each age cohort (2 to <12, or 12 to <18 years old).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 8

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 39 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications