慢性脫髓鞘多發性神經炎

The main purpose of this study is to evaluate the safety and efficacy of nipocalimab compared to placebo in delaying relapse in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) who initially respond to nipocalimab in Stage A.

液劑

Nipocalimab

084

MG/ML

Primary Outcome Measures
•Stage B: Time to First Occurrence of a Relapse Event

Each potential participant must satisfy all of the following criteria to be enrolled in the study:
Age
1. Criterion modified per Amendment 2.
1.1. Adults ≥ 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.
Type of Participant and Disease Characteristic
2. Diagnosed with CIDP according to criteria of the EAN/PNS 2021, progressing or
relapsing forms. CIDP diagnosis to be adjudicated by independent committee during
screening period.
3. Criterion modified per Amendment 6.
3.1 INCAT disability score between 2 and 9 at the Run-In Baseline visit for participants
entering Run-In, or Stage A Baseline visit for participants directly entering Stage A.
Participants with an INCAT score of 2 at trial entry must have this score exclusively from
the leg disability score.
4. Criterion modified per Amendment 4
4.1 Fulfilling any of the following treatment conditions:
a. Currently treated with oral CS ≤20 mg/day; or
b. Currently treated with pulsed CS, and/or IVIg or SCIg and the patient is
willing to discontinue no later than the Run-in Baseline visit; or
c. Currently treated with oral CS >20 mg/dayand the patient is willing to taper
to ≤20 mg/day during the run-in period; or
d. Without previous treatment (treatment naïve); or
e. Treatment with CS and/or IVIg or SCIg discontinued at least 3 months prior
to screening (untreated)
5. Active disease as determined by CIDP Disease Activity Status (CDAS) score ≥3.
6. Has sufficient venous access to allow drug administration by infusion and blood sampling
as per the protocol.
Vaccination History
7. Criterion modified per Amendment 1
7.1. It is recommended to be up to date on all age-appropriate vaccinations prior to
screening 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 (see also
Section 6.8.1).
Sex and Contraceptive/Barrier Requirements
8. A woman of childbearing potential must have a negative highly sensitive serum (b-human
chorionic gonadotropin [b-hCG]) at Screening and a negative urine pregnancy test at
Day1 prior to administration of study intervention.
9. Criterion modified per Amendment 1
9.1. A woman must be (as defined in Section 10.6, Appendix 6, Contraceptive and Barrier
Guidance)
Not of childbearing potential
Of childbearing potential and
Practicing a highly effective 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 must evaluate the potential for
contraceptive method failure (eg, noncompliance, recently initiated) in relationship
to the first dose of study intervention. Examples of highly effective methods of
contraception are located in Section 10.6, Appendix 6, Contraceptive and Barrier
Guidance.
Note: Local country/territory requirements will supersede if more stringent.
10. 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.
11. Criterion modified per Amendment 3
11.1 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). See Appendix 6.
12. Criterion modified per Amendment 4
Criterion modified per Amendment 6
12.1 A male participant must agree not to donate sperm or freeze for the purpose of
reproduction during the study and for a minimum of 90 days after receiving the last dose of
study intervention.
Informed Consent
13. Criterion modified per Amendment 3
13.1 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. Participants who initially provide consent and
subsequently withdraw it prior to enrollment in Run-in or Stage A (as applicable per Inclusion criterion 4) will be deemed as having failed this inclusion criterion. Must be
legal age of consent in the jurisdiction in which the study is taking place, at the time of
consent.
14. Criterion modified per Amendment 6.
14.1 Must be literate ie, able to read and write (this does not include physical incapacity
to write).

Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
Medical Conditions
1. Criterion modified per Amendment 3
1.1 Has a history of severe and/or uncontrolled hepatic (e.g.,
viral/alcoholic/autoimmune hepatitis/cirrhosis and/or metabolic liver disease),
gastrointestinal, renal, pulmonary, cardiovascular, psychiatric, neurological or
musculoskeletal disorder, hypertension and/or any other medical or uncontrolled
autoimmune disorder(s) (e.g., diabetes mellitus) or clinically significant abnormalities
in screening laboratory that might interfere with the patient’s full participation in the
study, or might jeopardize the safety of the participant or the validity of the study
results. Note: Any condition for which, in the opinion of the investigator, participation
would not be in the best interest of the participants (e.g., compromise well-being) or
that could prevent, limit, or confound the protocol-specified assessments.
2. Pure sensory CIDP or CISP (EAN/PNS definition).
3. Criterion modified per Amendment 3
3.1 Polyneuropathy of other causes, including the following: Multifocal motor
neuropathy (MMN); Monoclonal gammopathy of uncertain significance with
antimyelin associated glycoprotein (anti-MAG) immunoglobulin M (IgM) antibodies;
Hereditary motor neuropathy; Hereditary neuropathy with liability to pressure palsies
(HNPP); Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin
change syndromes; Lumbosacral radiculoplexus neuropathy; Polyneuropathy most
likely due to diabetes mellitus; Polyneuropathy most likely due to systemic illnesses;
Drug- or toxin-induced polyneuropathy. Note: A concomitant polyneuropathy of other
causes (e.g. a mild, stable diabetic polyneuropathy) is not necessarily exclusionary if
CIDP is confirmed as the main diagnosis, as determined by the investigator and
confirmed by the adjudication committee.
4. Any other disease that could better explain the patient's signs and symptoms, such as
significant persisting neurological deficits from stroke or central nervous system (CNS)
trauma or peripheral neuropathy from another cause such as connective tissue disease
or systemic lupus erythematosus.
5. Any history of myelopathy or evidence of central demyelination.
6. 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).
7. Has known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients
(refer to the IB).
8. Has shown a previous severe immediate hypersensitivity reaction, such as anaphylaxis
to therapeutic proteins (eg, mAbs).
9. Has experienced myocardial infarction, unstable ischemic heart disease, or stroke
within 12 weeks of screening.
10. 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.
11. Is (anatomically or functionally) asplenic.
12. 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.
13. Is planning to father a child while enrolled in this study or within 90 days after the last
dose of study intervention.
Prior/Concomitant Therapy
14. Criterion modified per Amendment 6
14.1 Treatment with the following:
Within 3 months (or 5 half-lives of the drug, whichever is longer) before
screening: plasma exchange or immunoadsorption, efgartigimod or other FcRn
inhibitors, any concomitant Fc-containing therapeutic agents (including factor or enzyme replacement), or other biological, or any other investigational
product.
Within 6 months before screening: rituximab, alemtuzumab, any other
monoclonal antibody, cyclophosphamide, interferon, tumor necrosis factoralpha
inhibitors, fingolimod, methotrexate, azathioprine, mycophenolate, and
any other immunomodulating or immunosuppressive medications.
Note: Inhaled, intra-articular, topical or ocular corticosteroids are not exclusionary.
Current participation in another nipocalimab study or previously exposed to
nipocalimab.
15. Criterion modified per Amendment 3
15.1 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 in this study. 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 study for
any SARS-CoV-2 (COVID-19) vaccine while participating in this study is not
permitted. For Bacille Calmette-Guérin (BCG) vaccine, see exclusion criterion 16.
16. Criterion modified per Amendment 1
16.1. Has had a BCG vaccination within 1 year of first administration of study
intervention.
Infections or Predisposition to Infections
17. Has a severe infection including opportunistic infections (eg, pneumonia, biliary tract
infection, diverticulitis, Clostridium difficile infection, cytomegalovirus,
pneumocystosis, aspergillosis, etc) 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.
18. Has a chronic infection (eg, bronchiectasis, chronic osteomyelitis, chronic
pyelonephritis) or requires chronic treatment with anti-infectives (eg, antibiotics,
antivirals).
19. Tests positive for hepatitis B virus (HBV) infection (see Appendix 3, [Section 10.3]).
20. Is seropositive for antibodies to hepatitis C virus (HCV), unless they satisfy 1 of the
following conditions:
Has a history of successful treatment, defined as being negative for HCV
ribonucleic acid (RNA) at least 24 weeks after completing antiviral treatment,
and has a negative HCV RNA test result at screening,
OR
While seropositive, has a negative HCV RNA test result at least 24 weeks prior
to screening and a negative HCV RNA test at screening.
21. History of being human immunodeficiency virus (HIV)1 or HIV2 antibody-positive, or
tests positive for HIV at screening.
22. Criterion amended per Amendment 1
22.1. COVID-19 infection:
During the 6 weeks prior to baseline, has had ANY of the following (regardless of
vaccination status):
a. confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
infection (test positive), OR
b. suspected SARS-CoV-2 infection (clinical features of COVID-19 without
documented test results), OR
c. close contact with a person with known or suspected SARS-CoV-2 infection:
Exception: may be included with a documented negative result for a validated
SARS-CoV-2 test
obtained at least 2 weeks after conditions (a), (b), (c) above (timed from
resolution of key clinical features if present, [eg, fever, cough, dyspnea]).
AND
with absence of ALL conditions (a), (b), (c) above during the period between
the negative test result and the baseline study visit.
NOTES on COVID-related exclusion:
The field of COVID-related testing (for presence of, and immunity to, the SARSCoV-
2 virus) is rapidly evolving. Additional testing may be performed as part of
screening and/or during the study if deemed necessary by the investigator and in
accordance with current regulations/guidance from authorities/standards of care.
Precaution: for those who may carry a higher risk for severe COVID-19 illness, follow
guidance from local health authorities when weighing the potential benefits and risks
of enrolling in the study, and during participation in the study.
23. Has a history of active granulomatous infection, including histoplasmosis or
coccidioidomycosis, before screening.
24. 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.
25. Had major surgery (eg, requiring general anesthesia [although not all procedures
requiring general anesthesia would necessarily be major]) 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.
Note: Participants with planned surgical procedures to be conducted under local
anesthesia may participate.
26. Has any condition for which, in the opinion of the investigator, participation would not
be in the best interest of the participant (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments.
27. Is an employee of the investigator or study site, with direct involvement in the proposed
study or other studies under the direction of that investigator or study site, as well as
family members of the employees or the investigator.
Medical Conditions
28. Has a history of an unprovoked pulmonary embolism within 1 year prior to screening
or history of recurrent DVT.
29. Has any of the following screening lab results:
ALT and/or AST concentrations ≥3 times the ULN for the laboratory conducting
the test
Serum albumin <3.2 g/dL