This study has been transitioned to CTIS with ID 2024-512785-33-00 check the CTIS register for the current data. Primary objective: To evaluate the clinical improvement of efgartigimod PH20 SC treatment compared with placebo, in addition to standard…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study endpoint is the total improvement score (TIS).
Secondary outcome
Key secondary endpoints:
• Time to reach TIS >=20 (first *minimal clinical improvement*)
• Percentage of participants with TIS >=20
• Time to reach TIS >=40 (first *moderate clinical improvement*)
• Percentage of participants with TIS >=40
• Change in manual muscle testing-8 (MMT8) score
• Change in Patient Global Assessment of Disease Activity (PGA)
• Change in Physician Global Assessment of Disease Activity (MDGA)
• Proportion of participants achieving target oral prednisone dosage of <=5 mg
(or equivalent)
For other secondary endpoints and exploratory endpoints please refer to the
study protocol
Background summary
IIM, also referred to as myositis, are inflammatory disorders of the skeletal
muscle. This heterogeneous group of diseases includes many subtypes with
varying pathologies. There is evidence that some IIM subtypes*specifically DM,
IMNM, and certain other subtypes of PM (ASyS)*are likely driven by IgG
autoantibodies (including myositis-specific antibodies [MSAs] and
myositis-associated antibodies [MAAs]).
Many patients with IIM have persistent impairment of muscle function, which
leads to difficulties in daily life activities and a low health-related quality
of life. The typical treatment for IIM is high-dose glucocorticoids combined
with immunosuppressive drugs. The deleterious long-term effects of
corticosteroids have been well established and include osteoporosis, cataracts,
and weight gain. There are no therapies approved by the United States Food and
Drug Administration (FDA) or the European regulatory authorities based on
results of randomized controlled trials for IMNM and PM. Only 1 licensed
treatment (10% intravenous immunoglobulin [IVIg]) is available for adults with
DM that was approved based on results of randomized controlled clinical
trials.Given efgartigimod*s mechanism of action of reducing IgG levels,
efgartigimod PH20 SC may benefit patients with these specific IIM subtypes.
Study objective
This study has been transitioned to CTIS with ID 2024-512785-33-00 check the CTIS register for the current data.
Primary objective: To evaluate the clinical improvement of efgartigimod PH20 SC
treatment compared with placebo, in addition to standard of care
immunomodulatory therapy.
Key secondary objectives:
• To evaluate additional measures of the efficacy of efgartigimod PH20 SC in
achieving clinical response
• To evaluate the effect of efgartigimod PH20 SC on muscle strength
• To evaluate the effect of efgartigimod PH20 SC on patient and physician
global assessments of disease activity
• To evaluate the steroid-sparing effect of efgartigimod PH20 SC (phase 3 stage
only)
For other secondary objectives and exploratory objectives please refer to the
study protocol.
Study design
This is a randomized, double-blinded, placebo-controlled, parallel group,
multicenter, operationally seamless phase 2/3 study to evaluate the efficacy,
safety, tolerability, PK, PD, and immunogenicity of efgartigimod PH20 SC in
adult participants with active IIM. This study consists of 2 distinct stages (a
phase 2 stage and a phase 3 stage) with separate cohorts of participants.
After screening, a 24-week (phase 2) or 52-week (phase 3) treatment period
follows, during which participants will be randomized to receive either
efgartigimod PH20 SC 1000 mg or matching placebo (with the same concentration
of rHuPH20) weekly in addition to their background treatment for IIM.
In both stages, during the treatment period, participants will receive weekly
SC fixed doses of IMP (either efgartigimod PH20 SC or matching placebo) except
in the last week (week 24 [phase 2] or week 52 [phase 3]) in which participants
will attend the final treatment period visit. At the end of the treatment
period (ie, week 24 [visit 7, phase 2] or week 52 [visit 14, phase 3]),
eligible participants may enroll in the open-label extension (OLE) study
ARGX-113-2011, in which all participants will be treated with efgartigimod PH20
SC. Otherwise, participants will continue a 56-day safety follow-up period.
Intervention
efgartigimod PH20 SC 1000 mg or matching placebo (with the same concentration
of rHuPH20)
Study burden and risks
The potential risks associated with efgartigimod PH20 SC are justified by the
anticipated benefits that may be afforded to participants with IIM in this
study and considering measures implemented to minimize risks. The favorable
balance between risks and anticipated efficacy/benefits supports the use of
efgartigimod PH20 SC in clinical development in IIM.
Please refer to protocol section 2.3 for the full risk/benefit assessment.
Industriepark Zwijnaarde 7
Zwijnaarde (Ghent) B-9052
BE
Industriepark Zwijnaarde 7
Zwijnaarde (Ghent) B-9052
BE
Listed location countries
Age
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:
a. Diagnosis of dermatomyositis (DM) or juvenile dermatomyositis (JDM), (age of
disease onset <18 years of age). The diagnosis date for juvenile
dermatomyositis 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)
• 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, LDH. aspartate aminotransaminase (AST), alanine
aminotransferase (ALT), based on central laboratory results
b. Electromyography demonstrating active disease 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
• 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:
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
• 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,
infectious myopathy, 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 study 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:
a. Hepatitis B virus (HBV)
b. Hepatitis C virus (HCV)
c. 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-512785-33-00 |
| EudraCT | EUCTR2021-001277-23-NL |
| CCMO | NL80454.018.22 |