Clinical Trials Register

Summary
EudraCT Number:	2020-005081-34
Sponsor's Protocol Code Number:	JAK-SPARE1
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-05-11
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2020-005081-34

A.3

Full title of the trial

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)

Eine randomisierte, doppelblinde, multizentrische Placebo-kontrollierte Phase III Studie mit parallelen Gruppen zur Beurteilung der Wirksamkeit und Sicherheit von Baricitinib zur Remissionsinduktion und als Glukokortikoid sparender Wirkstoff in Patienten mit früher Polymyalgia rheumatica (JAK-SPARE 1)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A randomized study to evaluate the efficacy and Safety of Baricitinib to induce Remission and to spare Glucocorticoids in subjects with new-onset Polymyalgia Rheumatica.

Eine randomisierte Studie zur Beurteilung der Wirksamkeit und Sicherheit von Baricitinib zur Remissionsinduktion und als Glukokortikoid sparender Wirkstoff in Patienten mit früher Polymyalgia rheumatica

A.3.2

Name or abbreviated title of the trial where available

JAK-SPARE1

A.4.1

Sponsor's protocol code number

JAK-SPARE1

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Medical University of Vienna
B.1.3.4	Country	Austria
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Medical University of Vienna
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Daniel Aletaha
B.5.2	Functional name of contact point	Principal Investigator
B.5.3	Address:
B.5.3.1	Street Address	Währinger Gürtel 18-20
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1090
B.5.3.4	Country	Austria
B.5.4	Telephone number	004314040043000
B.5.5	Fax number	004314040044360
B.5.6	E-mail	daniel.aletaha@meduniwien.ac.at

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Olumiant
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Olumiant
D.3.2	Product code	LY3009104
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BARICITINIB
D.3.9.1	CAS number	1187594-09-7
D.3.9.2	Current sponsor code	LY3009104
D.3.9.4	EV Substance Code	SUB180983
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BARICITINIB
D.3.9.1	CAS number	1187594-09-7
D.3.9.2	Current sponsor code	LY3009104
D.3.9.4	EV Substance Code	SUB180983
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Polymyalgia rheumatica (PMR)

E.1.1.1

Medical condition in easily understood language

Polymyalgia rheumatica (PMR)

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the 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.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The following inclusion criteria need to be fulfilled in order to be eligible for the study:
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 (see table 1) [19,20]
2. Diagnosis of PMR of maximum 3 weeks established at screening visit.
3. GC naïve1 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 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.

E.4

Principal exclusion criteria

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 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 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 randomization
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

E.5 End points

E.5.1

Primary end point(s)

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

E.5.1.1

Timepoint(s) of evaluation of this end point

See section E.5.1

E.5.2

Secondary end point(s)

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

E.5.2.1

Timepoint(s) of evaluation of this end point

See section E.5.2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

last scheduled visit for the last patient

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-06-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-05-19

P. End of Trial
P.	End of Trial Status	Ongoing

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