A study to investigate the efficacy and safety of efgartigimod PH20 SC in adult participants with active idiopathic inflammatory myopathy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Argenx

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

1 Mar 2023 → ongoing

Decision date (initial)

2024-08-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

argenx BV

External identifiers

EU CT number

2024-512785-33-00

EudraCT number

2021-001277-23

ClinicalTrials.gov

NCT05523167

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic, Others, Pharmacokinetic

To evaluate the clinical improvement of efgartigimod PH20 SC treatment compared with placebo, in addition to standard-of-care immunomodulatory therapy

Secondary objectives 6

1. 1. To evaluate additional measures of the efficacy of efgartigimod PH20 SC in achieving clinical response
2. 2. To evaluate the effect of efgartigimod PH20 SC on muscle strength
3. 3. To evaluate the effect of efgartigimod PH20 SC on patient and physician global assessments of disease activity
4. 4. To evaluate the steroid-sparing effect of efgartigimod PH20 SC
5. 5. To evaluate the effect of efgartigimod PH20 SC on muscle enzyme creatine kinase (CK)
6. 6. To assess the efficacy of efgartigimod PH20 SC in participants with dermatomyositis (DM)

Conditions and MedDRA coding

Active Idiopathic Inflammatory Myopathy (IIM)

Study design 2 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Ability to consent in the jurisdiction in which the study is taking place and capable of giving signed informed consent
2. A definite or probable clinical diagnosis of idiopathic inflammatory myopathy (IIM)
3. One of the following medical histories: (a) Diagnosis of dermatomyositis (DM) or juvenile dermatomyositis (JDM), (age of disease onset <18 years of age). The diagnosis date for JDM should not be >5 years from the screening date; (b) Diagnosis of polymyositis (PM) (including antisynthetase syndrome (ASyS)); (c) Diagnosis of immune-mediated necrotizing myopathy (IMNM)
4. Diagnosed with active disease as defined by the presence of at least 1 of the following criteria: (a) 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; (b) Electromyography demonstrating active disease performed within the past 3 months; (c) Active dermatomyositis (DM) skin rash; (d) Muscle biopsy indicative of active idiopathic inflammatory myopathy (IIM) (in the past 3 months); (e) Magnetic resonance imaging within the past 3 months indicative of active inflammation
5. Muscle weakness
6. Receiving a permitted background treatment for IIM
7. 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)

Exclusion criteria 19

1. A clinically significant active infection at screening
2. A COVID-19 polymerase chain reaction (PCR)-positive test before enrollment
3. 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
4. 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: (a) Basal cell or squamous cell skin cancer; (b) Carcinoma in situ of the cervix; (c) Carcinoma in situ of the breast; (d) Incidental histological finding of prostate cancer
5. Severe muscle damage
6. 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
7. Juvenile myositis (JDM) diagnosed > 5 years from screening or juvenile myositis with extensive calcinosis or severe calcinosis.
8. 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
9. Other inflammatory and noninflammatory myopathies: inclusion body myositis, infectious myopathy, overlap myositis, metabolic myopathies, muscle dystrophies or a family history of muscle dystrophy, druginduced or endocrine-induced myositis, and juvenile myositis (other than juvenile dermatomyositis (JDM))
10. 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
11. Known hypersensitivity reaction to investigational medicinal product (IMP) or 1 of its excipients
12. Received a live or live-attenuated vaccine less than 4 weeks before screening.
13. Positive serum test at screening for active viral infection with any of the following conditions: a. Hepatitis B virus (HBV); b. Hepatitis C virus (HCV); c. HIV
14. Participant has previously participated in an efgartigimod clinical trial and received at least 1 dose of investigational medicinal product (IMP).
15. Participant is concurrently participating in any other clinical study, including a noninterventional study.
16. Participant has a current or history (ie, within 12 months of screening) of alcohol, drug, or medication abuse.
17. Participant is pregnant or lactating or intends to become pregnant during the study.
18. Participant has severe renal impairment.
19. Participant is institutionalized by a court or other governmental order or is in a dependent relationship with the sponsor or investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean total improvement score (TIS) at week 52

Secondary endpoints 9

1. 1. Time to reach sustained TIS ≥40 (“moderate clinical improvement”)
2. 2. Percentage of participants with TIS ≥40 at week 52
3. 3. Percentage of participants with TIS ≥60 at week 52
4. 4. Change in manual muscle testing-8 (MMT8) score at week 52
5. 5. Change in Patient Global Assessment of Disease Activity (PGA) at week 52
6. 6. Change in Physician Global Assessment of Disease Activity (MDGA) at week 52
7. 7. Proportion of participants who have at least moderate improvement (≥40) in TIS at week 52 and adhere to an oral prednisone dosage of ≤5 mg/day (or equivalent) from week 44 onward
8. 8. Change in CK abnormality grades at week 52
9. 9. Change in Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score at week 52

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Argenx

Sponsor organisation

Argenx

Address

Industriepark-Zwijnaarde 7

City

Gent

Postcode

9052

Country

Belgium

Scientific contact point

Organisation

Argenx

Contact name

Regulatory

Public contact point

Organisation

Argenx

Contact name

Regulatory

Third parties 23

Locations

19 EU/EEA countries · 64 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 257 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

20 submissions — initial application plus substantial / non-substantial modifications