Clinical Trials Register

Summary
EudraCT Number:	2021-006562-20
Sponsor's Protocol Code Number:	JAKIPRA
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-08-08
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

Germany - BfArM

A.2

EudraCT number

2021-006562-20

A.3

Full title of the trial

JAK Inhibition in PReclinical Arthritis

Hemmung der Januskinasen im Vorstadium der rheumatoiden Arthritis

A.3.1

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

Inhibition of JAK Enzymes in early stage Joint inflammation

Hemmung der JAK-Enzyme bei frühen Formen von Gelenkentzündung

A.3.2

Name or abbreviated title of the trial where available

JAKIPRA

A.4.1

Sponsor's protocol code number

JAKIPRA

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	Universitätsklinikum Erlangen
B.1.3.4	Country	Germany
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	Lilly Deutschland GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Universitätsklinikum Erlangen
B.5.2	Functional name of contact point	Medizinische Klinik 3
B.5.3	Address:
B.5.3.1	Street Address	Ulmenweg 18
B.5.3.2	Town/ city	Erlangen
B.5.3.3	Post code	91054
B.5.3.4	Country	Germany
B.5.4	Telephone number	004991318543244
B.5.5	Fax number	004991318535784
B.5.6	E-mail	daniela.bohr@uk-erlangen.de

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 2 mg/4 mg Filmtabletten
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	Germany
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	Baricitinib blinded
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.3.9.4	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.3.11 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

Preclinical Phase of rheumatoid arthritis

Vorstadium der rheumatoiden Arthritis

E.1.1.1

Medical condition in easily understood language

Preclinical Phase of rheumatoid arthritis

Vorstadium der rheumatoiden Arthritis

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.1
E.1.2	Level	PT
E.1.2	Classification code	10039073
E.1.2	Term	Rheumatoid arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

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 evaluate the effect of JAK Inhibition with baricitinib in preclinical stage of arthritis

Untersuchung des Effekts einer Hemmung der Januskinasen durch Baricitinib im präklinischen Stadium der Arthritis

E.2.2

Secondary objectives of the trial

• To evaluate the effect of serological biomarkers such as pro-inflammatory cytokines, interferon signatures, bone biomarkers in preclinical arthritis
• To evaluate safety of baricitinib in preclinical stage of arthritis
• To identify (imaging and serological) biomarkers which may predict the course of disease in preclinical stage of arthritis
• To evaluate the effect of baricitinib on physical (hand) function in preclinical stage of disease

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Clinical: no arthritis in 76/78 joint count
• Imaging: ≥ 1 B-Mode or PD (Power Doppler) signal with ultrasound at one of the 76/78 joints or flexor/extensor tendons of hand or feet
• Autoantibodies: (2 different Autoantibodies are compulsory, one of them anti-CCP antibodies)
o Anti-CCP antibody positivity at Screening
o Anti-modified antibodies: (citrullinated vimentin, citVIM; citrullinated a-enolase, citENO; citrullinated fibrinogen alpha, citFIBa; citrullinated fibrinogen beta, citFIBb) (carbamylated vimentin, carVIM; ornithine acetylated vimentin (ac-orn VIM) and lysine acetylated Vimentin, ac-lys VIM)or RF
• Genetics: HLA Status with positive risk allel for RA such as HLA DRB1*01,*02,*03,…*015
• female or male patients, at least 18 and at most 64 years of age

• Klinisch: keine Arthritis im 76/78 joint count
• Bildgebung: ≥ 1 B-Mode or PD (Power Doppler) Signal im Ultraschall bei einem der 76/78 Gelenke oder Sehnen von Hand oder Fuß
• Autoantikörper: 2 verschiedene Autoantikörper sind obligatorisch, einer davon Anti-CCP Antikörper
o Anti-CCP Antibody positiv zum Screening
o Anti-modified antibodies: (citrullinated vimentin, citVIM; citrullinated a-enolase, citENO; citrullinated fibrinogen alpha, citFIBa; citrullinated fibrinogen beta, citFIBb) (carbamylated vimentin, carVIM; ornithine acetylated vimentin (ac-orn VIM) and lysine acetylated Vimentin, ac-lys VIM)or RF
• Genetics: HLA Status with positive risk allel for RA such as HLA DRB1*01,*02,*03,…*015
• weibliche oder männliche Patienten zwischen 18 und 64 Jahren

E.4

Principal exclusion criteria

• Clinically apparent arthritis (76/78 joint count)
• Fulfilment of ACR/EULAR 2010 Classification Criteria for RA
• Any previous therapy with bDMARD/tsDMARD/cDMARD
• Ongoing pregnancy status or breast-feeding
• Contraindication for Baricitinib treatment according to its SmPC
• Any malignancy risk factor (e.g. current malignancy or history of malignancy)
• Any active, chronic or recurrent infection
• Any pre-existing condition that constitutes a risk factor for major adverse cardiovascular events (e.g. history of stroke, coronary heart disease, myocardial infarction, current or past long-time smoker)
• Any known VTE risk factor (e.g. previous VTE/LE or inherited coagulation disorder)

• Klinische Zeichen der Arthritis (76/78 joint count)
• Erfüllen der ACR/EULAR 2010 Classification Criteria für RA
• Vorangegangene Therapie mit bDMARD/tsDMARD/cDMARD
• Schwangerschaft/Stillzeit
• Kontraindikationen für eine Behandlung mit Baricitinib (gemäß SmPC)
• aktive chronische bzw. rezidivierende Infektion
• MACE-Risikofaktoren (z.B. Schlaganfall, KHK, Herzinfarkt in der medizinischen Vorgeschichte, langjähriger Nikotinkonsum)
• Risikofaktoren für venöse Thrombembolien (z.B. Thrombose/Lungenembolie in der medizinischen Vorgeschichte, angeborene Gerinnungsstörung)

E.5 End points

E.5.1

Primary end point(s)

Number of patients with development of arthritis

E.5.1.1

Timepoint(s) of evaluation of this end point

week 48

E.5.2

Secondary end point(s)

• Number of patients with development of arthritis at week 24
• Fulfillment of the ACR/EULAR 2010 RA classification criteria
• Imaging:
o Ultrasound: Number of participants without signs of PD Synovitis or PD Tenosynovitis at week 24 and 48 compared to baseline and compared within both groups
• Explorative serological biomarkers: (week 24 and week 48 compared to baseline)
o Change in anti CCP2 antibody levels (RE/ml)
o Change in anti CCP2 antibodies in HLA-defined subgroups
o Glycosylation profile of total IgG, and CCP2 antibodies
o Number and frequency of total and CCP2-specific B cells
o MS-based unbiased metabolic profiling of plasma metabolites
o Changes in GBP1 levels
• Clinical outcomes, physical function and PROs:
o Patients without tender joints at week 48 compared to baseline
o Joint count 76/78; HAQ; SDAI/CDAI/DAS28-CRP
o Pain: VAS global, VAS pain, VAS physician
o Subjective (SACRAH, sMHQ) and objective (moberg-pick up test (MPUT)) hand function
o Safety

E.5.2.1

Timepoint(s) of evaluation of this end point

week 24 / week 48 compared to baseline

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

Yes

E.6.4

Safety

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

LSLV

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

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.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)

Standard of care

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

2022-10-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-04-11

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

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