IRB Study Number 23-1318
Status Recruiting
Phase Phase 2
Institute Neurological Institute
Description
To evaluate the efficacy of nipocalimab compared to placebo in delaying relapse in participants with CIDP who initially respond to nipocalimab.
Inclusion Criteria
- 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.
- 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.
- 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.
- Fulfilling any of the following treatment conditions: Currently treated with oral CS ≤20 mg/day; or 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 Currently treated with oral CS >20 mg/dayand the patient is willing to taperto ≤20 mg/day during the run-in period; or Without previous treatment (treatment naïve); or Treatment with CS and/or IVIg or SCIg discontinued at least 3 months prior to screening (untreated).
- Active disease as determined by CIDP Disease Activity Status (CDAS) score ≥3.
- Has sufficient venous access to allow drug administration by infusion and blood sampling as per the protocol.
- 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.
- 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.
- A woman must be: 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.
- 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.
- 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).
- 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.
- 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.
- Must be literate ie, able to read and write (this does not include physical incapacity to write).
Exclusion Criteria
- 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.
- Pure sensory CIDP or CISP (EAN/PNS definition).
- 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.
- 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.
- Any history of myelopathy or evidence of central demyelination.
- 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).
- Has known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients.
- Has shown a previous severe immediate hypersensitivity reaction, such as anaphylaxis to therapeutic proteins (eg, mAbs).
- Has experienced myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks of screening.
- 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.
- Is (anatomically or functionally) asplenic.
- 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.
- Is planning to father a child while enrolled in this study or within 90 days after the last dose of study intervention.
- 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. Inhaled, intra-articular, topical or ocular corticosteroids are not exclusionary. Current participation in another nipocalimab study or previously exposed to nipocalimab.
- 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.
- Has had a BCG vaccination within 1 year of first administration of study intervention.
- 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.
- Has a chronic infection (eg, bronchiectasis, chronic osteomyelitis, chronic pyelonephritis) or requires chronic treatment with anti-infectives (eg, antibiotics, antivirals).
- Tests positive for hepatitis B virus (HBV) infection).
- 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.
- History of being human immunodeficiency virus (HIV)1 or HIV2 antibody-positive, or tests positive for HIV at screening.
- 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.
- Has a history of active granulomatous infection, including histoplasmosis or coccidioidomycosis, before screening.
- 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.
- 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.
- 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.
- 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.
- Has a history of an unprovoked pulmonary embolism within 1 year prior to screening or history of recurrent DVT.
- 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
