Clinical Trials

Inclusion Criteria:

• Aged at least 18 years (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the informed consent.
• A definite or probable clinical diagnosis of IIM under the 2017 EULAR/ACR classification criteria.
• One of the following medical histories:
  • Diagnosis of DM or juvenile DM (JDM), fulfilling the 2017 EULAR/ACR criteria for DM or JDM (age of disease onset 5 years from the screening date;
  • Diagnosis of PM (including ASyS), having either of the following:
    • A prior muscle biopsy diagnostic for IIM;
    • A positive test at the central laboratory for at least 1 anti-aminoacyl-tRNA synthetase MSA (-Jo-1, -PL-7, -PL-12, -EJ, -OJ).
    • Participants with PM overlap with Sjögren’s syndrome must meet the ACR/EULAR 2016 classification criteria for Sjögren’s syndrome and will be included only if the muscle biopsy does not demonstrate any of the following:
      • P62 (+) inclusions, rimmed vacuoles, or increased number of ragged red fibers and cytochrome oxidase fibers for the patient’s age;
      • Note: Participants with a clinical diagnosis of PM who have a negative MSA result and participants with a clinical diagnosis of PM-Sjögren’s overlap regardless of their MSA result will be included after adjudication by an independent committee selected for their expertise in IIM. Details of this process are described in the biopsy adjudication charter.
    • Diagnosis of IMNM, meeting the 2017 European Neuromuscular Center classification criteria, 11 and having any of the following:
      • Anti–signal recognition particle (SRP) positive (at the central laboratory) myopathy;
      • Anti–3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) positive (at the central laboratory) myopathy;
      • A prior muscle biopsy with pathological features of IMNM;
      • Note: Participants with a clinical diagnosis of IMNM who have negative anti-SRP and anti-HMGCR results will be included after adjudication by an independent committee selected for their expertise in IIM. Details of this process are described in the biopsy adjudication charter.
  • Active disease as defined by the presence of at least 1 of the following criteria:
    • Abnormal levels of at least 1 of the following enzymes: CK (≥ 4×upper limit of normal [ULN]), aldolase (≥ 4 ×ULN), lactate dehydrogenase (≥ 4×ULN), AST (≥ 4×ULN), or ALT (≥ 4×ULN), based on central laboratory results;
    • Electromyography demonstrating active disease within the past 3 months;
    • Active DM skin rash (Gottron’s papules, Gottron’s signs, or heliotrope rash) or CDASI ≥ 7 (phase 2 stage) or ≥ 14 (phase 3 stage) at screening;
    • Muscle biopsy indicative of active IIM in the past 3 months;
    • Magnetic resonance imaging within the past 3 months indicative of active inflammation.
• Muscle weakness as assessed by an MMT8 score of < 142/150 and abnormalities in any 2 of the other 5 CSMs:
  • MDGA ≥ 2;
  • PGA ≥ 2;
  • Extramuscular global ≥ 2;
  • HAQ-DI ≥ 0.25;
  • Muscle enzyme ≥ 1.5×ULN.
• Receiving a permitted background treatment for IIM. Permitted background treatment includes:
  • OCS; 1 antimalarial (hydroxychloroquine, quinacrine, or chloroquine); or 1 of the following immunosuppressants: methotrexate, azathioprine, mycophenolate mofetil, mycophenolic acid, tacrolimus, cyclosporine, leflunomide, or mizoribine. Participants may receive a combination of either OCS and up to 1 antimalarial or OCS and up to 1 immunosuppressant;
  • Permitted background treatment must meet the following dose duration(s):
    • Immunosuppressants or antimalarials administered for at least 12 weeks before screening, and at a stable dose for at least score of 8 weeks before screening and then through baseline:
      • Participants who stopped treatment with an immunosuppressant or an antimalarial are eligible if their last dose was > 8 (except for leflunomide);
      • Participants who stopped treatment with leflunomide are eligible if their last dose was > 12 weeks before screening unless leflunomide washout treatment was used, in which case participants are eligible if the washout treatment was completed > 4 weeks before screening;
        • Note: The medical monitor (MM) should be contacted if a participant is receiving Chinese traditional medicine to discuss any possible immunosuppressive properties thereof.
    • OCS (≤ 20 mg prednisone or dose equivalent) initiated > 8 weeks before screening and at a stable dose for ≥ 4 weeks before screening through baseline:
      • Participants who stopped treatment with OCS before enrollment are eligible if the last dose of the steroid was > 4 weeks before screening;
    • Concurrent stable (> 2 weeks before screening) use of topical corticosteroid (or other immunomodulator) therapy is permitted if used for a non–IIM-related condition;
    • Note: If a participant is receiving both OCS and an additional agent, the dose durations described for both (a) and (b) must be met.
• Contraceptive use by nonsterilized male participants and WOCBP will be consistent with local regulations, where available, for individuals participating in clinical studies. WOCBP must have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline to establish the nonpregnant state before receiving IMP.
  • The contraceptive requirements for nonsterilized males and WOCBP are described in Section 10.4.2.
• Capable of giving signed informed consen which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol.

Exclusion Criteria:

• A clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening.
• A COVID-19 polymerase chain reaction (PCR)-positive test < 72 hours before enrollment:
  • COVID-19 testing will be done only if the participant is symptomatic or required by applicable law. In these cases, a negative PCR test (central or local laboratory) is required within 72 hours before enrollment and should occur regardless of a participant’s vaccination status.
• Any other known autoimmune disease that, in the investigator’s opinion, would interfere with an accurate assessment of clinical symptoms of IIM or put the patient at undue risk.
• A history of malignancy unless considered cured by adequate treatment, with no evidence of recurrence for ≥ 3 years before the first administration of IMP. Adequately treated participants with the following cancers can be included at any time:
  • Basal cell or squamous cell skin cancer;
  • Carcinoma in situ of the cervix;
  • Carcinoma in situ of the breast;
  • Incidental histological finding of prostate cancer (TNM stage T1a or T1b);
  • Note: Because patients with IIM have an increased risk of an associated malignancy, it is recommended that participants in the study comply with and are current with local recommendations for cancer screening procedures (based on their age, gender, and autoantibodies).
• Severe muscle damage defined as a global muscle damage score of > 5 on a 10-cm visual analog scale (VAS) scale on the Myositis Damage Index (MDI).
• Glucocorticoid-induced myopathy that the investigator considers the primary cause of muscle weakness or permanent weakness linked to a non-IIM cause.
• JDM diagnosed > 5 years from screening or JDM with extensive calcinosis (defined as calcinosis involving the torso or 2 extremities) or severe calcinosis (indicated by a calcinosis associated with severe loss of function).
• Uncontrolled interstitial lung disease or any other uncontrolled IIM manifestation that, in the opinion of the investigator, would be likely to require treatment with prohibited medication (eg, cyclophosphamide) during the study.
• Other inflammatory and noninflammatory myopathies: inclusion body myositis (based on the biopsy or when the weakness affects the finger and/or the wrist flexors out of proportion to shoulder abductors), overlap myositis (connective tissue disease–associated myositis, except an overlap with Sjögren’s syndrome, which is allowed provided that the biopsy does not demonstrate any of the features listed in inclusion criterion 3b), metabolic myopathies, muscle dystrophies or a family history of muscle dystrophy, drug-induced or endocrine-induced myositis (except statin-induced IMNM), and juvenile myositis (other than JDM).
• Clinically significant disease, recent major surgery (within 3 months of screening) or intends to have surgery during the study, or has any other condition in the opinion of the investigator that could confound the results of the trial or put the patient at undue risk.
• Known hypersensitivity reaction to IMP or 1 of its excipients.
• Received a live or live-attenuated vaccine less than 4 weeks before screening. The receipt of other types of vaccines at any time before screening is not considered exclusionary. It is recommended that participants are up to date with vaccinations before the first dose of IMP.
• Lack of clinical response to plasmapheresis/plasma exchange (PLEX).
• Positive serum test at screening for active viral infection with any of the following conditions:
  • Hepatitis B virus (HBV) indicative of an acute or chronic infection, unless associated with a negative HBV DNA test (https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf);
  • Hepatitis C virus (HCV) based on HCV antibody assay, unless associated with a negative HCV RNA test;
  • HIV based on test results associated with either:
    • An AIDS-defining condition or a CD4 count of ≤ 200 cells/mm^3;
    • No adequate treatment with antiretroviral therapy.
• Any of the following prior therapy or procedures:
  • Treatment within 2 weeks before screening: topical corticosteroids or topical immunomodulators (eg, tacrolimus) for IIM-related rash;
  • Treatment within 4 weeks before screening: local corticosteroid injections (intra-articular, bursa, and tendon sheath injections), anakinra, etanercept, Janus kinase (JAK) inhibitors, intramuscular or IV corticosteroids, PLEX, immunoadsorption;
  • Treatment within 8 weeks before screening: SC or intramuscular corticosteroid precursors;
  • Treatment within 12 weeks before screening: IVIg, SCIg, tocilizumab, abatacept, infliximab, adalimumab, golimumab, certolizumab, ustekinumab;
  • Treatment within 24 weeks before screening: rituximab or other anti-CD20 antibody, cyclophosphamide;
  • Use of a nonbiologic investigational product within 12 weeks or 5 half-lives (whichever is longer) before screening, unless the drug washout is specified in the protocol;
  • Use of a biologic therapy and/or monoclonal antibody (including biologic investigational product) within 24 weeks or 5 half-lives (whichever is longer) before screening, unless the drug washout is specified in the protocol;
  • Treatment with OCS dose > 20 mg prednisone or dose equivalent i. Treatment with > 1 immunosuppressant, > 1 antimalarial, or a combination of an immunosuppressant and an antimalarial
• Participant has previously participated in an efgartigimod clinical trial and received at least 1 dose of IMP.
• Participant is concurrently participating in any other clinical study, including a noninterventional study.
• Participant has IgG < 4 g/L at screening.
• Participant has a current or history (ie, within 12 months of screening) of alcohol, drug, or medication abuse.
• Participant is pregnant or lactating or intends to become pregnant during the study.
• Participant has severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m^2 ) at screening.
• Participant is institutionalized by a court or other governmental order or is in a dependent relationship with the sponsor or investigator.