IVIG-Spare Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

23 Jan 2025 → ongoing

Decision date (initial)

2024-10-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the proportion of patients in IVIG-free stable disease activity at week 16 after randomization across two study arms comparing Upadacitinib 30 mg vs Placebo.

Secondary objectives 1

1. Exploratory secondary outcomes include time to first flare, time to reinstitution of IVIG, manual muscle test (MMT-8) as well as creatine kinase (CK) values (absolute and change from baseline) at week 16 and 20, patient reported outcomes including fatigue, disease activity, and quality of life, and cumulative dose of steroids at week 16 and 20.

Conditions and MedDRA coding

Polymyositis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Written informed consent
2. 2. Female and male subjects ≥ 18 and <=65 years of age at the time of signing the informed consent
3. 3. Patients with clinical diagnosis of idiopathic inflammatory myopathies (IIM; including PM, DM, IMNM, ASyS, OM)
4. 4. Receiving IVIG at stable dose and interval for at least 12 weeks before screening
5. 5. Stable disease activity according to the discretion of the treating physician for at least 3 months
6. 6. 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
7. 7. Willing and being capable of understanding and following the study procedures
8. 8. 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 32

1. 1. Conditions other than IIM requiring continuous or intermittent treatment with IVIG such as primary or secondary immune deficiencies.
2. 10. 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)
3. 11. Plasmapheresis within 12 weeks prior to screening.
4. 12. 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
5. 13. Severe hepatic impairment.
6. 14. 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
7. 15. Symptomatic herpes simplex infection at the time of randomization
8. 16. Symptomatic herpes zoster infection within 12 weeks prior to randomization
9. 17. History of disseminated/complicated herpes zoster (for example, multidermatomal involvement, ophthalmic zoster, CNS involvement, or post-herpetic neuralgia)
10. 18. Serologic evidence of current or past Hepatitis B, or Hepatitis C infection
11. 19. Evidence of HIV infection and/or positive HIV antibodies
12. 2. Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis) that by discretion of investigator might interfere with conduction of the study
13. 20. 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.
14. 21. Are largely or wholly incapacitated permitting little or no self-care, such as being bedridden or confined to wheelchair
15. 22. 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
16. 23. Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation
17. 24. Any medical or psychological condition that in the opinion of the Principal Investigator would interfere with safe completion of the trial
18. 25. 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
19. 26. Pregnant women or nursing (breast feeding) mothers
20. 27. 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.
21. 28. 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)
22. 29. Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation
23. 3. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
24. 30. Patients with lack of peripheral venous access
25. 31. Patients with known allergy or intolerance to the study drug or its’ excipients
26. 4. 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.
27. 5. 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.
28. 6. History of recurrent (≥ 2) VTE (DVT/PE)
29. 7. 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.
30. 8. History of gastrointestinal organ perforation.
31. 9. 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).
32. Patients currently smoking

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To assess the proportion of patients in IVIG-free stable disease activity at week 16 after randomization across two study arms comparing Upadacitinib 30 mg vs Placebo.

Secondary endpoints 8

1. • Difference in proportion of patients in IVIG-free stable disease activity at week 20 between patients with Upadacitinib versus Placebo
2. Different proportion of patients with IVIG-free stable disease activity at week 16 and 20 using different definitions of disease worsening: (1) worsening PhGA by ≥ 2 cm NRS and worsening MMT-8 by ≥ 20%, or (2) worsening EmGA by ≥ 2 cm NRS or (3) a worsening of 3 of the 6 core set measures (HAQ-DI, MMT-8, CK, PhGA, PtGA, EmGA) by ≥ 30%.
3. • Difference in time to first flare between patients with Upadacitinib versus Placebo
4. • Difference of manual muscle test between Upadacitinib and Placebo at week 16 and week 20
5. • Difference of patient reported outcomes, including 0- 10 numeric rating scale (NRS) of PtGA, EmGA, muscular pain, fatigue, dyspnoe and dysphagia; Quality of life, Health Assessment Questionaire Disability (HAQ-DI) between Upadacitinib and Placebo at week 16 and week 20
6. • Difference cumulative dose of steroids between patients with Upadacitinib versus Placebo at week 16 and 20
7. • Difference in laboratory parameters of values (CK, ALT, AST, LDH and aldolase) between Upadacitinib and Placebo at week 16 and week 20
8. • Differences in safety profile according to number of adverse events and organ systems (haematologic, hepatic, gastrointestinal, infections)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Division of Rheumatology

Public contact point

Organisation

Medical University Of Vienna

Contact name

Division of Rheumatology

Locations

1 EU/EEA country · 1 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 14 files

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

Application history

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