Efficacy and Safety Evaluation of Baricitinib for Remission Induction and Glucocorticoid Sparing in New-Onset Polymyalgia Rheumatica
- Trial ID
- 2024-518556-22-00
- Protocol
- JAK-SPARE 1
- Sponsor
- Medical University Of Vienna
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** and safety of **Baricitinib** compared with placebo in achieving glucocorticoid-free remission in patients with new-onset **polymyalgia rheumatica**. This is clinically relevant as it aims to provide an alternative treatment strategy that could potentially reduce the dependency on glucocorticoids, which are associated with significant side effects when used long-term. The study is designed as a randomized, double-blind, placebo-controlled, parallel-group, multi-center, Phase III trial, ensuring robust and reliable results.
Participants
The clinical trial involves participants diagnosed with **polymyalgia rheumatica**. The study population includes both male and female subjects aged 50 years and older. Participants are required to be in general good health, with no significant comorbidities that could interfere with the study outcomes. The trial does not involve a vulnerable population. The sponsor has not provided the total number of participants. Selection criteria include a recent diagnosis of polymyalgia rheumatica, confirmed by the investigator, and a maximum of three weeks on glucocorticoid treatment at the time of screening. Participants must be willing to adhere to a specified glucocorticoid tapering regimen and take preventive measures against glucocorticoid-induced bone loss. Lifestyle considerations such as diet and physical activity are not specified, but participants must be capable of understanding and following study procedures. Both male and female participants must agree to use effective contraception unless they are not of childbearing potential.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel group, multi-center, Phase III study. The primary objective is to evaluate the efficacy and safety of **baricitinib** as a remission-induction and glucocorticoid-sparing regimen in subjects with new-onset **polymyalgia rheumatica**. The trial will assess the efficacy of baricitinib compared to placebo, alongside a rapidly tapered glucocorticoid (GC) treatment, with GC-free remission as the primary outcome. The study is expected to conclude by December 31, 2025, with recruitment starting on October 17, 2024.
Participants will be involved in the study for a maximum treatment period of 44 weeks. The trial includes several key visits: an inclusion (screening) visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be confirmed based on criteria such as a diagnosis of polymyalgia rheumatica within three weeks, willingness to follow a specified treatment regimen, and the ability to provide informed consent. Follow-up visits will occur at weeks 12, 16, 28, and 44 to monitor the proportion of subjects in GC-free remission, cumulative GC doses, number of relapses, and other secondary endpoints. The end-of-study visit will finalize data collection and assess the overall outcomes.
Participant involvement is expected to last up to 44 weeks, depending on individual response and adherence to the study protocol. Conditions that may lead to early termination from the study include non-compliance with the study regimen, withdrawal of consent, or the occurrence of adverse events that necessitate discontinuation. The study will utilize Olumiant 2 mg and 4 mg film-coated tablets, as well as a placebo designed to match the appearance of baricitinib tablets, administered orally. The trial will ensure that all investigational medicinal products are appropriately packaged and manufactured for clinical trial use, with no commercial debossing on the tablets.
Treatment
The clinical trial involves the administration of **Olumiant** in two different dosages as the experimental medication. **Olumiant 2 mg film-coated tablets** contain the active substance **baricitinib**, a chemical compound also known by the synonyms LY-3009104 and INCB-028050. The pharmaceutical form is a film-coated tablet, and the medication is administered orally. The maximum daily dose is 2 mg, with a total maximum dose of 168 mg over a treatment period of up to 12 weeks. The investigational medicinal product (IMP) is specifically packaged for clinical trial use, with the drug product and excipients potentially differing in facilities, specifications, methods, shelf-life, and packaging from commercial versions. The tablets do not have commercial debossing, ensuring suitability for clinical trial use.
Additionally, the trial includes **Olumiant 4 mg film-coated tablets**, which also contain **baricitinib** as the active substance. This formulation is similarly administered orally, with a maximum daily dose of 4 mg and a total maximum dose of 1232 mg over a treatment period of up to 44 weeks. The IMP is manufactured with the same commercial drug substance and unit formula as Olumiant, with adjustments made for clinical trial packaging and specifications. The absence of commercial debossing on the tablets is maintained for trial appropriateness.
A **placebo** is utilized in the study to match the appearance of the baricitinib 4 mg and 2 mg tablets. The placebo is designed to be indistinguishable from the active medication in terms of appearance, ensuring the integrity of the double-blind study design. The placebo does not contain any active pharmaceutical ingredients and serves as a control to evaluate the efficacy and safety of baricitinib in the treatment of new-onset polymyalgia rheumatica.
Efficacy
The efficacy of the investigational product, **Baricitinib**, in the clinical trial will be assessed through a series of predefined endpoints. The primary endpoint is the proportion of subjects achieving glucocorticoid (GC) free remission at week 16. Secondary endpoints include the proportion of subjects in GC free remission at weeks 12, 28, and 44, cumulative GC doses at these timepoints, and the number of relapses per patient. Additional secondary endpoints involve the time to first and second relapse, glucocorticoid dose intensity at week 16, and various patient-reported outcomes such as the SF-36, FACIT-Fatigue, HAQ, Patient Global Assessment of Disease Activity, and patient assessment of pain.
Investigator-reported outcomes will also be evaluated, including the Evaluator Global Assessment of disease activity, duration and severity of morning stiffness, and a semiquantitative elevation of upper limbs’ scale. Laboratory markers of inflammation, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), will be measured, alongside the Polymyalgia Rheumatica Activity Score (PMR-AS). The occurrence of adverse events, serious adverse events, and GC-related adverse events will be monitored, as well as changes in vital signs, hematology, and clinical chemistry parameters.
These efficacy parameters will be collected and analyzed at specified timepoints throughout the trial, including weeks 12, 16, 28, and 44. The trial is designed as a randomized, double-blind, placebo-controlled, parallel group, multi-center, Phase III study, with the primary objective of evaluating the efficacy and safety of Baricitinib as a remission-induction and glucocorticoid-sparing regimen in subjects with new-onset Polymyalgia Rheumatica.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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
- Diagnosis of PMR of maximum 3 weeks at screening visit
- GC naïve or on GC treatment for a maximum of 3 weeks at screening with an initial dose of maximum 25 mg/day
- Willing and able to receive oral prednisone/prednisolone 20 mg/day at randomization and to follow a pre-specified tapering regimen
- Willing to receive treatment for prevention of GC-induced bone loss
- Willing and being able to understand and follow the study procedures
- 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
- Written informed consent
- Female and Male subjects from ≥ 50 years old and higher
Exclusion Criteria
- 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
- 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
- Other inflammatory rheumatic diseases (e.g. rheumatoid arthritis)
- 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
- 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
- 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
- Have a history of recurrent (≥ 2) VTE (DVT/PE)
- 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
- 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)
- 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)
- Have received plasmapheresis within 12 weeks of screening
- 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
- 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
- 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
- Have a symptomatic herpes simplex at the time of randomization
- Have had symptomatic herpes zoster infection within 12 weeks prior to randomizatio
- Have a history of disseminated/complicated herpes zoster (for example, multidermatomal involvement, ophthalmic zoster, CNS involvement, or post-herpetic neuralgia)
- Have serologic evidence of current or past Hepatitis B, or Hepatitis C
- Have evidence of HIV infection and/or positive HIV antibodies
- 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; in Czech Republic this would also include active smoking patients or patients with a history of long-term smoking
- Pregnant women or nursing (breast feeding) mothers
- Patients with reproductive potential not willing to use an effective method of contraception
- 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
- Patients with lack of peripheral venous access
- Patients with known allergy or intolerance to the study drug or its’ excipients
- For Centers in Czech Republic only: Patients above 65 years of age at screening visit
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 17 Oct 2024 | 25 |
 Czechia | Not Recruiting | 17 Oct 2024 | 3 |
 Italy | Not Recruiting | 17 Oct 2024 | 18 |
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 |
|---|---|---|---|---|---|---|
Olumiant 2 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 2 | 12 | PRD4760216 |
Olumiant 4 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | 4 | 44 | PRD4765061 |
placebo to match baricitinib 4mg and 2mg in appearance | Placebo | N/A | — | — | — | N/A |