A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-center, Phase III Study to Evaluate the Efficacy and Safety of Baricitinib as a Remission-Induction and Glucocorticoid-Sparing Regimen in Subjects with New-Onset Polymyalgia Rheumatica (JAK-SPARE 1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

10 May 2022 → 13 Apr 2026

Decision date (initial)

2024-12-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518556-22-00

EudraCT number

2020-005081-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess efficacy and safety of Baricitinib compared with Placebo on top of rapidly tapered GC treatment in a double-blind controlled study, with GC free remission of disease as primary outcome

Conditions and MedDRA coding

polymyalgia rheumatica

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Diagnosis of PMR as confirmed by the investigator at screening and at baseline, fulfilment (also in retrospect) of the provisional 2012 ACR-EULAR classification criteria
2. Diagnosis of PMR of maximum 3 weeks at screening visit
3. GC naïve or on GC treatment for a maximum of 3 weeks at screening with an initial dose of maximum 25 mg/day
4. Willing and able to receive oral prednisone/prednisolone 20 mg/day at randomization and to follow a pre-specified tapering regimen
5. Willing to receive treatment for prevention of GC-induced bone loss
6. Willing and being able to understand and follow the study procedures
7. Male and female subjects agreeing to conduct efficient contraception (unless they have no childbearing potential, means a. Women who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation b. Women aged 55 years or older who are not on hormone therapy and who have had at least 6 months of spontaneous amenorrhea c. Women aged 55 years or older who have a diagnosis of menopause
8. Written informed consent
9. Female and Male subjects from ≥ 50 years old and higher

Exclusion criteria 32

1. Evidence of GCA (cranial or large vessel) as indicated by unequivocal clinical symptoms (except PMR), imaging and/or biopsy results. Routine screening of eligible PMR patients for GCA with imaging methods or temporal artery biopsy is not recommended
2. Conditions other than PMR requiring continuous or intermittent treatment with oral or parenteral GCs or parenteral administration of GCs, unless the last exposure to GCs was >1 months before screening
3. Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis)
4. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
5. Have 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
6. Have experienced any of the following VTE (DVT/pulmonary embolism, myocardial infarction, unstable ischemic heart disease stroke, or New York Heart Association Stage III/IV heart failure within 12 weeks of screening. For Centres within Czech Republic and Italy patients with any history of it must not be included
7. Have a history of recurrent (≥ 2) VTE (DVT/PE)
8. Have a history or presence of 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
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)
10. Previous treatment with baricitinib, tofacitinib, upadacitinib, filgotinib or tocilizumab (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on a case-by-case basis)
11. Have received plasmapheresis within 12 weeks of screening
12. Have screening laboratory test values, including thyroid-stimulating hormone (TSH), outside the reference range for the population that, in the opinion of the investigator, pose an unacceptable risk for the patient´s participation in the study. Patients who are receiving thyroxine as replacement therapy may participate in the study, provided stable therapy has been administered for ≥ 12 weeks and TSH is within the laboratory´s range. Patients who have TSH marginally outside the laboratory´s normal reference range and are receiving stable thyroxine replacement therapy may participate if the treating physician has documented that the thyroxine replacement therapy is adequate for the patient
13. Have any of the following specific abnormalities on screening laboratory tests: a. ALT or AST >2 x ULN b. Alkaline phosphatase (ALP) ≥2 x ULN c. Total bilirubin ≥ 1.5 x ULN d. Hemoglobin <9 g/dL (90.0 g/L) 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] <1200 cells/ µL (<1.20 x 103/ µL or <1.20 GI/L) g. Lymphopenia (lymphocyte count <500 cells/µL) (<50 x 103/ µL or <50GI/L) h. Thrombocytopenia (platelets <100,000 cells/µL) (<100 x 103/µL or <100 GI/L) i. eGFR <60 mL/min/1.73 m2 (Bedside Schwartz formula 2009) 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
14. Have a 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
15. Have a symptomatic herpes simplex at the time of randomization
16. Have had symptomatic herpes zoster infection within 12 weeks prior to randomizatio
17. Have a history of disseminated/complicated herpes zoster (for example, multidermatomal involvement, ophthalmic zoster, CNS involvement, or post-herpetic neuralgia)
18. Have serologic evidence of current or past Hepatitis B, or Hepatitis C
19. Have evidence of HIV infection and/or positive HIV antibodies
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.
21. Are largely or wholly incapacitated permitting little or no self-care, such as being bedridden or confined to wheelchair
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
23. Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation
24. Any medical or psychological condition that in the opinion of the Principal Investigator would interfere with safe completion of the trial
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; in Czech Republic this would also include active smoking patients or patients with a history of long-term smoking
26. Pregnant women or nursing (breast feeding) mothers
27. Patients with reproductive potential not willing to use an effective method of contraception
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
29. Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation
30. Patients with lack of peripheral venous access
31. Patients with known allergy or intolerance to the study drug or its’ excipients
32. For Centers in Czech Republic only: Patients above 65 years of age at screening visit

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects in GC free remission at week 16 (Part I)

Secondary endpoints 10

1. Proportion of subjects in GC free remission at week 12 (Part I), 28 (Part II) and 44 (Part III)
2. Cumulative GC doses at weeks 12, 16 (Part I), 28 (Part II) and 44 (Part III)
3. Number of relapses per patient at weeks 12, 16 (Part I), 28 (Part II) and 44 (Part III)
4. Time to first and second relapse
5. Glucocorticoid dose intensity (absolute and relative) at week 16
6. Patient reported outcomes including SF-36, FACIT-Fatigue, HAQ, Patient Global Assessment of Disease Activity (PGA), Patient assessment of pain
7. Investigator reported outcomes including Evaluator Global Assessment of disease activity (EGA), duration and severity of Morning Stiffness, semiquantitative elevation of upper limbs’ scale
8. Laboratory markers of inflammation including ESR and CRP
9. Polymyalgia Rheumatica Activity Score (PMR-AS)
10. Occurrence of adverse events and serious adverse events, incidence of GC-related adverse events, changes in vital signs, haematology and clinical chemistry parameter

Investigational products

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

Test 2

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

Department of Medicine III, Division of Rheumatology

Public contact point

Organisation

Medical University Of Vienna

Contact name

Department of Medicine III, Division of Rheumatology

Locations

3 EU/EEA countries · 5 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 9 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