Efficacy and Safety of Upadacitinib in Idiopathic Inflammatory Myopathies Post-IVIG Withdrawal: A Randomized, Double-Blind, Placebo-Controlled Phase II Study
- Trial ID
- 2024-513681-19-00
- Protocol
- IVIG-SPARE Trial
- Sponsor
- Medical University Of Vienna
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** and safety of **Upadacitinib** in patients with idiopathic inflammatory myopathies, specifically assessing the proportion of patients achieving IVIG-free stable disease activity at week 16 after randomization. This is clinically relevant as it aims to determine the potential of Upadacitinib to maintain disease stability without the need for intravenous immunoglobulins (IVIG), which could reduce treatment burden and associated risks for patients.
Secondary objectives include exploring the time to first flare, time to reinstitution of IVIG, and changes in manual muscle test (MMT-8) and creatine kinase (CK) values at weeks 16 and 20. Additionally, patient-reported outcomes such as fatigue, disease activity, quality of life, and cumulative steroid dose at weeks 16 and 20 will be assessed. These outcomes provide a comprehensive understanding of the treatment's impact on disease progression and patient quality of life.
Participants
The clinical trial involves a study population comprising both **female** and male subjects aged between 18 and 65 years. Participants are individuals diagnosed with idiopathic inflammatory myopathies, including **polymyositis**, dermatomyositis, antisynthetase syndrome, overlap myositis, and immune-mediating necrotising myopathy. The trial does not include a vulnerable population. Participants are required to have stable disease activity and must have been receiving intravenous immunoglobulin (IVIG) at a stable dose and interval for at least 12 weeks prior to screening. Additionally, they should be on a permitted background treatment for idiopathic inflammatory myopathies, such as immunosuppressive drugs, antimalarials, or corticosteroids, with a stable dose and interval for at least 12 weeks before enrollment. The total number of participants is not provided by the sponsor. Lifestyle considerations, such as diet and physical activity, are not specified in the available data.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled** Phase II study to evaluate the efficacy and safety of **upadacitinib** in patients with idiopathic inflammatory myopathies, including polymyositis, dermatomyositis, antisynthetase syndrome, overlap myositis, and immune-mediated necrotizing myopathy. The trial aims to assess the proportion of patients achieving IVIG-free stable disease activity at week 16 after randomization, comparing upadacitinib 30 mg with a placebo. The trial is expected to commence recruitment on October 1, 2024, and conclude by May 31, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and stable disease activity. Following randomization, participants will attend regular follow-up visits to monitor their response to treatment and any adverse events. The primary endpoint will be evaluated at week 16, with additional assessments at week 20 to measure secondary endpoints, including differences in disease activity, time to first flare, and patient-reported outcomes. The end-of-study visit will occur at the conclusion of the trial to gather final data and ensure participant safety.
The expected duration of participant involvement is approximately 20 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. Participants will receive either upadacitinib or a placebo, administered orally as prolonged-release tablets or gelatin capsules filled with maltodextrin, respectively. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.
Treatment
The clinical trial involves the administration of **RINVOQ 30 mg prolonged-release tablets**, which contain the active substance **upadacitinib**. Upadacitinib is a chemical compound with the chemical name (3S,4R)-3-ethyl-4-(1,5,7,10-tetrazatricyclo[7.3.0.0]dodeca-2(6),3,7,9,11-pentaen-12-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, also known as ABT-494. The pharmaceutical form of the medication is a prolonged-release tablet, designed to release the active ingredient over an extended period. The medication is administered orally, with a maximum daily dose of 30 mg and a total maximum dose of 4200 mg over a treatment period of up to 20 weeks. The trial aims to evaluate the efficacy and safety of upadacitinib in patients with idiopathic inflammatory myopathies following the withdrawal of intravenous immunoglobulins (IVIG).
The study also includes a **placebo** group, where participants receive gelatine capsules filled with maltodextrin. The placebo is designed to mimic the appearance and administration route of the active treatment, ensuring the study remains double-blind. The placebo does not contain any active pharmaceutical ingredients and serves as a control to assess the true efficacy of upadacitinib. The placebo capsules are administered orally, following the same schedule as the active treatment, to maintain consistency across study arms. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.
Efficacy
The efficacy of Upadacitinib in patients with idiopathic inflammatory myopathies will be assessed through a randomized, double-blind, placebo-controlled Phase II clinical trial. The primary endpoint is the proportion of patients achieving **IVIG-free stable disease activity** at week 16 after randomization, comparing Upadacitinib 30 mg to placebo. Secondary endpoints include the difference in the proportion of patients with IVIG-free stable disease activity at week 20, using various definitions of disease worsening, such as worsening PhGA by ≥ 2 cm NRS and worsening MMT-8 by ≥ 20%, or worsening EmGA by ≥ 2 cm NRS, or a worsening of 3 of the 6 core set measures (HAQ-DI, MMT-8, CK, PhGA, PtGA, EmGA) by ≥ 30%. Additional secondary endpoints involve the difference in time to first flare, manual muscle test scores, patient-reported outcomes, cumulative steroid dose, and laboratory parameters (CK, ALT, AST, LDH, and aldolase) between Upadacitinib and placebo at weeks 16 and 20. The safety profile will also be evaluated based on the number of adverse events and affected organ systems.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written informed consent
- Female and male subjects ≥ 18 and <=65 years of age at the time of signing the informed consent
- Patients with clinical diagnosis of idiopathic inflammatory myopathies (IIM; including PM, DM, IMNM, ASyS, OM)
- Receiving IVIG at stable dose and interval for at least 12 weeks before screening
- Stable disease activity according to the discretion of the treating physician for at least 3 months
- Receiving a permitted background treatment for IIM including immunosuppressive drugs or antimalarials, corticosteroids (up to 10mg/day prednisone äquivalent ) with stable dose and interval for at least 12 weeks before enrollment
- Willing and being capable of understanding and following the study procedures
- Female subjects agreeing to conduct efficient contraception, (unless they have no childbearing potential, means: o Women who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation o Women aged 55 years or older who are not on hormone therapy and who have had at least 6 months of spontaneous amenorrhea o Women aged 55 years or older who have a diagnosis of menopause o Women with amenorrhoe >12 months)
Exclusion Criteria
- Conditions other than IIM requiring continuous or intermittent treatment with IVIG such as primary or secondary immune deficiencies.
- Previous treatment with a Janus kinase (JAK) inhibitor or tyrosine kinase (TYK) inhibitor (e.g. Baricitinib, Tofacitinib, Filgotinib, Deucravacitinib (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on a case-by-case basis)
- Plasmapheresis within 12 weeks prior to screening.
- Any of the following specific abnormalities on screening laboratory tests: a. ALT or AST >3 x ULN (if not explained by IIM disease activity) b. Alkaline phosphatase (ALP) >3 x ULN c. Total bilirubin ≥ 1.5 x ULN d. Hemoglobin <8 g/dL e. Total white blood cell count <2500 cells/µL (<2.50 x 103 / µL or <2.50 GI/L) f. Neutropenia (absolute neutrophil count [ANC] <1000 cells/ µL (<1.0 x 109/ L or <1.20 GI/L) g. Lymphopenia (lymphocyte count <500 cells/µL) (<0.5 x 109/L or <50GI/L) h. Thrombocytopenia (platelets <100,000 cells/µL) (<100 x 103/µL or <100 GI/L) i. eGFR <30 mL/min/1.73 m2 In the case of any of the aforementioned laboratory abnormalities, the test may be repeated once by the central laboratory during screening and values resulting from repeat testing may be accepted for enrolment eligibility if they meet the eligibility criterion
- Severe hepatic impairment.
- Current or recent (< 4 weeks prior to randomization) clinically serious viral, bacterial, fungal or parasitic infection or any other active or recent infection, that in the opinion of the investigator would pose an unacceptable risk to the patient if participating in the study
- Symptomatic herpes simplex infection at the time of randomization
- Symptomatic herpes zoster infection within 12 weeks prior to randomization
- History of disseminated/complicated herpes zoster (for example, multidermatomal involvement, ophthalmic zoster, CNS involvement, or post-herpetic neuralgia)
- Serologic evidence of current or past Hepatitis B, or Hepatitis C infection
- Evidence of HIV infection and/or positive HIV antibodies
- Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis) that by discretion of investigator might interfere with conduction of the study
- Positive QuantiFERON TB test, history of Tuberculosis, or active Tuberculosis-infection (without at least 4 weeks of adequate therapy for Tuberculosis and no history of re-exposure since their treatment was completed); patients must have no clinical features of active TB and have a screening chest x-ray with no evidence of active TB.
- Are largely or wholly incapacitated permitting little or no self-care, such as being bedridden or confined to wheelchair
- Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
- Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation
- Any medical or psychological condition that in the opinion of the Principal Investigator would interfere with safe completion of the trial
- History of any malignancy prior to screening and patients with an increased risk of malignancy, which, according to the investigator, would pose an unacceptable risk to the patient if participating in the study
- Pregnant women or nursing (breast feeding) mothers
- Female patients with reproductive potential not willing to use an effective method of contraception (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilisation) and are not willing to continue this precaution for the duration of the study until 6 months after receiving the last medication dose.
- Have a history of intravenous drug abuse, other illicit drug abuse, or chronic alcohol abuse within the 2 years prior to screening or are concurrently using, or expected to use during the study, illicit drugs (including marijuana)
- Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
- Patients with lack of peripheral venous access
- Patients with known allergy or intolerance to the study drug or its’ excipients
- Screening electrocardiogram (ECG) abnormalities that, in the opinion of the investigator, are clinically significant and indicate an unacceptable risk for the patient´s participation in the study.
- History of venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE); myocardial infarction, unstable ischemic heart disease stroke, or New York Heart Association Stage III/IV heart failure.
- History of recurrent (≥ 2) VTE (DVT/PE)
- Past or current cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders, or any other serious and/or unstable illness that in the opinion of the investigator could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.
- History of gastrointestinal organ perforation.
- Immunization with a live/attenuated vaccine within 12 weeks prior to baseline or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination at the discretion of the investigator).
- Patients currently smoking
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Recruiting | 01 Oct 2024 | 10 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
RINVOQ 30 mg prolonged-release tablets | Test | PROLONGED-RELEASE TABLETS | ORAL | 30 | 20 | PRD9181732 |
Placebo consists of gelatine capsules filled with maltodextrin | Placebo | N/A | — | — | — | N/A |