Clinical Study in Active Idiopathic Inflammatory Myopathy (IIM)
CLINICALTRIALS.GOV ID: NCT05523167
A Phase 2/3* Randomized, Double-Blinded, Placebo-Controlled, Parallel-Group, 2-Arm, Multicenter, Operationally Seamless Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of Efgartigimod PH20 SC in Participants Aged 18 Years and Older With Active Idiopathic Inflammatory Myopathy
*Currently recruiting for Phase 3
About Active Idiopathic Inflammatory Myopathy (IIM)
Idiopathic Inflammatory Myopathy (IIM), also referred to as myositis, is an inflammatory disorder of the skeletal muscle. This includes many subtypes with varying pathologies.2 There is evidence that some IIM subtypes—specifically dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), and certain other subtypes of polymyositis (ASyS)—are likely driven by IgG autoantibodies (including myositis-specific antibodies [MSAs] and myositis-associated antibodies [MAAs]).3,4,5,6
Many patients with IIM have persistent impairment of muscle function, which leads to difficulties in daily life activities and a low quality of life.2 There are currently no approved treatments for myositis, which presents an unmet need for effective long term treatment of the disease.
About the Investigational Therapy
Efgartigimod alfa is an antibody fragment crystallizable receptor (FcRn) antagonist in clinical development for treating patients with severe autoimmune diseases mediated by pathogenic immunoglobulin G (IgG) autoantibodies.7
Efgartigimod alfa with recombinant human hyaluronidase for subcutaneous injection, also known as efgartigimod PH20 SC, is not approved by any regulatory agency for Active Idiopathic Inflammatory Myopathy (IIM) as safety and efficacy have not been established.
Efgartigimod alfa Proposed Mechanism of Action
A study to investigate the efficacy and safety of efgartigimod PH20 SC in adult participants with active idiopathic inflammatory myopathy (also known as myositis)
Primary Outcome Measure
Total improvement score (TIS); measured on a [0,100] scale. Higher scores represent improvement; zero indicates no improvement or worsening (from baseline)
Study Design
Participants will be randomized 1:1 within each stratum to receive either efgartigimod PH20 SC‡ on top of background treatment
OR
placebo PH20 SC‡ on top of background treatment
‡ rHuPH20 (or PH20) is a permeation enhancer
SCREENING PERIOD
The study team will determine a patient's eligibility to participate.
TREATMENT PERIOD:
52-weeks (Phase 3 stage)
Participants will be randomized to receive either efgartigimod PH20 SC 1000 mg or placebo weekly in addition to their background treatment for IIM. Administrations will be given during the scheduled site visits and at participant’s homes in between visits (if feasible and allowed).
OPEN LABEL EXTENSION STUDY* or SAFETY FOLLOW UP PERIOD:
At the end of the treatment period, eligible participants may enroll in the open-label extension (OLE) study, in which all participants may have the opportunity to be treated with efgartigimod PH20 SC. Otherwise, participants will continue a 56-day safety follow-up period.
* (ALKIVIA+) ClinicalTrials.gov ID NCT05979441
Efgartigimod alfa with recombinant human hyaluronidase, also known as efgartigimod PH20 SC, is not approved by any regulatory agency for Active Idiopathic Inflammatory Myopathy (IIM) as safety and efficacy have not been established.
Select Eligibility Criteria§
§The following criteria listed below is an overview and is not all inclusive. Please see link for full study eligibility details: clinicaltrials.gov/NCT05523167.
Select Inclusion Criteria:
- A definite or probable clinical diagnosis of idiopathic inflammatory myopathy (IIM)
- One of the following medical histories: Diagnosis of dermatomyositis (DM) or juvenile dermatomyositis (JDM), Diagnosis of polymyositis (PM) (including antisynthetase syndrome (ASyS)), Diagnosis of immune-mediated necrotizing myopathy (IMNM)
- Diagnosed with 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: creatine kinase (CK), aldolase, lactate dehydrogenase, aspartate aminotransaminase (AST), alanine aminotransferase (ALT), based on central laboratory results; Electromyography demonstrating active disease within the past 3 months; Active DM skin rash; Muscle biopsy indicative of IIM in the past 3 months; Magnetic resonance imaging within the past 3 months indicative of active inflammation
- Muscle weakness
- Receiving a permitted background treatment for IIM
Select Exclusion Criteria:
- A clinically significant active infection at screening
- 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 the investigational medicinal product (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
- Severe muscle damage
- Glucocorticoid-induced myopathy that the investigator considers the primary cause of muscle weakness or permanent weakness linked to a non-IIM cause
- 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 during the study
- Other inflammatory and noninflammatory myopathies: inclusion body myositis, overlap myositis, metabolic myopathies, muscle dystrophies or a family history of muscle dystrophy, drug-induced or endocrine induced myositis, and juvenile myositis (other than JDM)
- Clinically significant disease, recent major surgery or intends to have surgery during the study
- Positive serum test at screening for active viral infection with any of the following conditions: Hepatitis B virus (HBV); Hepatitis C virus (HCV); HIV
- Participant is pregnant or lactating or intends to become pregnant during the study
References:
1. https://clinicaltrials.gov/ct2/show/NCT05523167
2. Schmidt J. Current Classification and Management of Inflammatory Myopathies. Journal of Neuromuscular Diseases 5. (2018) 109–129.
3. Zaizen Y et al. Respiratory Research (2023) 24:86 https://doi.org/10.1186/s12931-023-02362-0
4. Julien S et al. Rheumatology 2023 /advance-article/doi/10.1093
5. Preuße C et al. Acta Neuropathologica (2022) 144:353–372 https://doi.org/10.1007/s00401-022-02438-z
6. Aggarwal R. et al. Rheumatology 2016;55:991_999 doi:10.1093/rheumatology/kev44
7. Ulrichts P, et al. J Clin Invest. 2018;128(10):4372-4386
ALKIVIA Study HCP Webpage_Global_V2_21 February 2024
MED-EU-a118-2300001
