Efficacy and Safety Study of Nipocalimab IV Infusions for Adults With Generalized Myasthenia Gravis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

26 Nov 2021 → ongoing

Decision date (initial)

2023-09-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Janssen Research & Development, LLC

External identifiers

EU CT number

2023-504152-97-00

EudraCT number

2020-005732-29

ClinicalTrials.gov

NCT04951622

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Pharmacodynamic

To evaluate the efficacy of nipocalimab compared to placebo based on the Myasthenia Gravis-Activities of Daily Living (MG-ADL) scale, in seropositive generalized myasthenia gravis (gMG) participants when treatment is taken as directed.
Sub study: To evaluate the PD effect of SC nipocalimab compared to IV nipocalimab based on IgG levels in all gMG participants when treatment is taken as directed

Conditions and MedDRA coding

Generalized Myasthenia Gravis

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & 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 22

1. RANDOMIZED PHASE: ≥18 years of age at the time of consent, and as applicable, must also meet the legal age of consent in the jurisdiction in which the study is taking place.
2. RANDOMIZED PHASE: Diagnosis of MG with generalized muscle weakness meeting the clinical criteria for gMG as defined by the MGFA Clinical Classification Class II a/b, III a/b, or IVa/b at screening.(seronegative participants are no longer being recruited to the main study; all participants must have a positive serologic test for a gMG related pathogenic autoantibody (anti-AChR and/or anti-MuSK autoantibodies), confirmed prior to enrollment. Per Amendment 5, gMG participants (anti-AChR positive and antiAChR negative, including anti-MuSK positive, anti-LRP4 positive and seronegative) who have not previously received nipocalimab will be enrolled in SC Cohort 2, with the number of participants enrolled in SC Cohort 2 who are both anti-AChR negative and anti-MuSK negative not exceeding 10% of the total.
3. RANDOMIZED PHASE: MG-ADL score of ≥6 at screening and baseline.
4. RANDOMIZED PHASE: Has suboptimal response to current stable therapy for gMG according to the investigator. Stable therapy is defined in the Protocol
5. RANDOMIZED PHASE: 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 from baseline through the double-blind placebo-controlled phase of the study.
6. RANDOMIZED PHASE: 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 Adults Aged 19 Years or Older, United States. (https://www.cdc.gov) OR must be vaccinated as per country- or territory-specific guidelines or local regulations.
7. RANDOMIZED PHASE: Has sufficient venous access to allow drug administration by infusion and blood sampling as per the protocol.
8. RANDOMIZED PHASE: Is recommended to be up to date on all age-appropriate vaccinations prior to screening as per routine local medical guidelines. It is strongly recommended that participants will have completed a locally-approved (or emergency use-authorized) COVID-19 vaccination regimen 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.
9. RANDOMIZED PHASE: Criterion removed per Amendment 1.
10. RANDOMIZED PHASE: A woman of childbearing potential must have a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) at Screening and a negative urine pregnancy test at Day 1 prior to administration of study intervention.
11. RANDOMIZED PHASE: Criterion modified per Amendment 1. 11.1 A woman must be (as defined in Section 10.6, Appendix 6, Contraceptive and Barrier Guidance) a. Not of childbearing potential b. Of childbearing potential and - Practicing a highly effective, preferably user-independent method of contraception (failure rate of <1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study intervention and until 30 days after last dose - the end of relevant systemic exposure. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
12. RANDOMIZED PHASE: A woman must agree not to donate eggs (ova, oocytes), or freeze for future use for the purposes of assisted reproduction, during the study and for a period of 30 days after the administration of study intervention.
13. RANDOMIZED PHASE: A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for at least 90 days after receiving the last administration of study intervention. In addition, male participants with partners who are a woman of childbearing potential are highly encouraged to inform their partner to use highly effective contraception methods that result in a low failure rate (less than 1% per year).
14. RANDOMIZED PHASE: A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum 90 days after receiving the last administration of study intervention.
15. RANDOMIZED PHASE: Must sign an ICF indicating that the participant understands the purpose of, and procedures required for, the study and is willing to voluntarily participate in the study and comply with all study procedures.
16. RADOMIZED PHASE: Must be able to read and write.
17. OLE PHASE: The investigator has confirmed that the participant is not receiving, or has not received since the interruption of the Phase 2 study, any medication that might put the participant at risk when receiving nipocalimab or might interfere with the assessment of the safety of nipocalimab.
18. OLE PHASE: Randomized inclusion point 6
19. OLE PHASE: Randomized inclusion point 7
20. OLE PHASE: Is recommended to be up to date on all age-appropriate vaccinations prior to screening as per routine local medical guidelines. It is strongly recommended to have COVID-19 vaccination at least 2 weeks before the study visits.
21. OLE PHASE: Sex and Contraceptive/Barrier Requirements as outlined in Double-blind Placebo-Controlled Phase inclusion criteria # 9, #10, #11, #12, #13, and #14 above.
22. OLE PHASE: Randomized inclusion point 15

Exclusion criteria 32

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, psychiatric, neurological musculoskeletal disorder, hypertension, any other medical disorder(s) (eg, diabetes mellitus), or clinically significant abnormalities in screening laboratory, that might interfere with the patient’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.
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.
6. Has had a thymectomy within 12 months prior to screening, or thymectomy is planned during the study.
7. Has current or a history of any neurologic disorder other than MG that might interfere with the accuracy of study assessments.
8. Currently has a malignancy or has a history of malignancy within 3 years before screening.
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. Is planning to father a child while enrolled in this study or donate sperm within 90 days after the last administration of study intervention.
13. Is currently breastfeeding, pregnant, intends to become pregnant during the study, or is planning egg donation during the study or within 30 days after the last dose of study intervention.
14. History of moderate or severe substance or alcohol use.
15. Is currently taking eculizumab or other novel immune agents, IgG Fc-related protein therapeutics, or Fc-conjugated therapeutic agents, including factor or enzyme replacement.
16. Has received, rituximab within 6 months prior to first administration of study intervention. This criterion does not apply to returning Phase 2 participants.
17. 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
18. Has received plasmapheresis, immunoadsorption therapy, or IVIg within 6 weeks prior to baseline.
19. 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.
20. 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. This criterion does not apply to returning Phase 2 participants.
21. Has previously received nipocalimab. This criterion does not apply to returning Phase 2 participants.
22. Has received an investigational intervention (including investigational vaccines) within 3 months or 5 half-lives (whichever is longer) or used an invasive investigational medical device within 3 months before the planned first dose administration of study intervention
23. Has a severe infection including opportunistic infections requiring parenteral anti-infectives and/or hospitalization, and/or is assessed as serious/clinically significant by the investigator, within 8 weeks prior to screening. The participant may be rescreened after the 8-week exclusionary period has passed.
24. Has a chronic infection or requires chronic treatment with anti-infectives.
25. Tests positive for hepatitis B virus infection.
26. Is seropositive for antibodies to hepatitis C virus (HCV), unless they satisfy 1 of the conditions listed in the protocol.
27. History of being human immunodeficiency virus (HIV)1 or HIV2 antibody-positive, or tests positive for HIV at screening.
28. COVID-19 infection or contact with infected persons as per the protocol.
29. Has current suicidal ideation evidenced by a “yes” response to Questions 4 or 5 in the Suicidal Ideation section of the C-SSRS at screening or baseline, or a history of active suicidal ideation or suicidal behavior in the past year prior to screening.
30. Had major surgery (eg, requiring general anesthesia) within 3 months before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study.
31. Criterion removed per Amendment 1.
32. Is an employee of the investigator or study site.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Average change from baseline (screening and Day 1) in MG-ADL total score over Weeks 22, 23 and 24. Sub study: Percent change in total IgG levels from pre-first nipocalimab dose Day 1 to Week 8 (Day 57)

Investigational products

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

Test 3

Placebo 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 13

Locations

9 EU/EEA countries · 33 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 138 files

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

Application history

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