A Study to Investigate the Efficacy and Safety of Efgartigimod PH20 SC in Adult Participants With Active Idiopathic Inflammatory Myopathy. (ALKIVIA)

• ClinicalTrials.gov Identifier: NCT05523167
• Recruitment Status: Recruiting
• First Posted: August 31, 2022
• Last Update Posted: April 8, 2024
• Sponsor: argenx
• Information provided by (Responsible Party): argenx

Tracking Information

• First Submitted Date: August 30, 2022
• First Posted Date: August 31, 2022
• Last Update Posted Date: April 8, 2024
• Actual Study Start Date: October 12, 2022
• Estimated Primary Completion Date: December 1, 2026 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 6, 2022): Total improvement score (TIS); measured on a [0,100] scale. Higher scores represent improvement; zero indicates no improvement or worsening (from baseline). [ Time Frame: phase 2: 24 weeks; phase 3: 52 weeks ]
• Original Primary Outcome Measures (submitted: August 30, 2022): Total improvement score (TIS) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]

Current Secondary Outcome Measures (submitted: July 6, 2023)

• Time to reach TIS ≥ 20 (first "minimal clinical improvement") [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Percentage of participants with TIS ≥ 20 [ Time Frame: phase 2: 24 weeks; phase 3: 52 weeks ]
• Time to reach TIS ≥ 40 (first "moderate clinical improvement") [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Percentage of participants with TIS ≥ 40 [ Time Frame: phase 2: 24 weeks; phase 3: 52 weeks ]
• Change in manual muscle testing-8 (MMT8) score [ Time Frame: phase 2: 24 weeks; phase 3: 52 weeks ]
• Change in Patient Global Assessment of Disease Activity (PGA) [ Time Frame: phase 2: 24 weeks; phase 3: 52 weeks ]
• Change in Physician Global Assessment of Disease Activity (MDGA) [ Time Frame: phase 2: 24 weeks; phase 3: 52 weeks ]
• Proportion of participants achieving target dose of ≤ 5 mg (prednisone equivalent) [ Time Frame: phase 2: 24 weeks; phase 3: 52 weeks ]

Original Secondary Outcome Measures (submitted: August 30, 2022)

• Time to reach TIS ≥ 20 (first "minimal clinical improvement") [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Percentage of participants with TIS ≥ 20 [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Time to reach TIS ≥ 40 (first "moderate clinical improvement") [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Percentage of participants with TIS ≥ 40 [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in manual muscle testing-8 (MMT8) score [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in Patient Global Assessment of Disease Activity (PGA) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in Physician Global Assessment of Disease Activity (MDGA) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in Health Assessment Questionnaire Disability Index (HAQ-DI) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in steroid dose from baseline to last visit [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Proportion of participants achieving target dose of ≤ 5 mg (prednisone equivalent) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in the Extramuscular Global Assessment [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in abbreviated handheld dynamometry [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in Patient Global Impression of Severity (PGI-S) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Patient Global Impression of Change (PGI-C) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in Clinical Global Impression of Severity (CGI-S) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Clinical Global Impression of Change (CGI-C) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in the Myositis Functional Index (FI-3) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in Patient-Reported Outcomes Information System (PROMIS) Pain Interference 6a v1.0 [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in pain numeric rating scale (NRS) assessing worst pain in the past 7 days [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in (PROMIS) Fatigue 7a v1.0 [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in Fatigue NRS assessing worst physical fatigue in the past 7 days [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in PROMIS Physical Function 8b v2.0 [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in the Physical Functioning subscale and Physical Component Summary scores of the 36-Item Short Form Survey version 2 (SF-36v2) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Composite Glucocorticoid Toxicity Index (C-GTI) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in EQ-5D-5L utilities [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in EQ-5D-5L VAS [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Change in the most abnormal enzyme in each participant [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Proportion of participants who meet protocol-defined worsening criteria [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Time to worsening [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Efgartigimod serum concentrations [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Total IgG levels [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Prevalence of antidrug antibodies (ADA) against efgartigimod and antibodies against rHuPH20 [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]
• Incidence of treatment-emergent AEs (TEAEs), AESIs, and serious AEs (SAEs) [ Time Frame: phase 2: up to 24 weeks; phase 3: up to 52 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Investigate the Efficacy and Safety of Efgartigimod PH20 SC in Adult Participants With Active Idiopathic Inflammatory Myopathy.
• Official Title: 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
• Brief Summary: This study's purpose is to measure the treatment response from efgartigimod PH20 SC compared with placebo in participants with Idiopathic Inflammatory Myopathy (IIM). Participants with the IIM subtypes of dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), or certain other subtypes of polymyositis (PM; including antisynthetase syndrome [ASyS]) will be included in the study. Treatment response will be measured by Total improvement score (TIS). Additional information can be found on https://myositis-study.com/.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Active Idiopathic Inflammatory Myopathy
• Myositis
• Dermatomyositis
• Polymyositis
• Immune-Mediated Necrotizing Myopathy
• Antisynthetase Syndrome

Intervention

• Biological: EFG PH20 SC
  Subcutaneous injection of efgartigimod coformulated with rHuPH20, a permeation enhancer
• Other: PBO
  Subcutaneous injection of placebo coformulated with rHuPH20, a permeation enhancer

Study Arms

• Experimental: EFG PH20 SC
  participants receiving efgartigimod PH20 SC on top of background treatment
  Intervention: Biological: EFG PH20 SC
• Placebo Comparator: PBO PH20 SC
  participants receiving placebo PH20 SC on top of background treatment
  Intervention: Other: PBO

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 30, 2022): 240
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 1, 2027
• Estimated Primary Completion Date: December 1, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Ability to consent in the jurisdiction in which the study is taking place and capable of giving signed informed consent.
• 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 dermatomyositis (DM) skin rash; Muscle biopsy indicative of active idiopathic inflammatory myopathy (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 idiopathic inflammatory myopathy.
• Contraceptive use consistent with local regulations, where available, for individuals participating in clinical studies. Women of childbearing potential must have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline before receiving investigational medicinal product (IMP).

The full list of inclusion criteria can be found in the protocol.

Exclusion Criteria:

• A clinically significant active infection at screening
• A COVID-19 polymerase chain reaction (PCR)-positive test before enrollment
• Any other known autoimmune disease that, in the investigator's opinion, would interfere with an accurate assessment of clinical symptoms of idiopathic inflammatory myopathy (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-idiopathic inflammatory myopathy (IIM) cause
• Juvenile myositis (JDM) diagnosed > 5 years from screening or juvenile myositis with extensive calcinosis or severe calcinosis.
• Uncontrolled interstitial lung disease or any other uncontrolled idiopathic inflammatory myopathy (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 juvenile dermatomyositis (JDM))
• Clinically significant disease, recent major surgery 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 investigational medicinal product (IMP) or 1 of its excipients
• Received a live or live-attenuated vaccine less than 4 weeks before screening.
• 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 has previously participated in an efgartigimod clinical trial and received at least 1 dose of investigational medicinal product (IMP).
• Participant is concurrently participating in any other clinical study, including a noninterventional study.
• 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 .
• Participant is institutionalized by a court or other governmental order or is in a dependent relationship with the sponsor or investigator.

The full list of exclusion criteria can be found in the protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sabine Coppieters, MD; 857-350-4834; ClinicalTrials@argenx.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Cyprus, Denmark, France, Georgia, Germany, Greece, Hungary, Ireland, Italy, Korea, Republic of, Lithuania, Mexico, Netherlands, Peru, Poland, Portugal, Serbia, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05523167
• Other Study ID Numbers: ARGX-113-2007
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: argenx
• Original Responsible Party: Same as current
• Current Study Sponsor: argenx
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: argenx
• Verification Date: April 2024