Inhibition of JAK enzymes in early stage joint inflammation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Erlangen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

6 Sep 2023 → ongoing

Decision date (initial)

2024-05-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514026-23-00

EudraCT number

2021-006562-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

to evaluate the effect of JAK inhibition with baricitinib in preclinical stage of arthritis

Secondary objectives 4

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

Conditions and MedDRA coding

preclinical phase of rheumatoid arthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Female or male patients, at least 18 and at most 64 years of age
2. Clinical: no arthritis in 76/78 joint count
3. Imaging: ≥ 1 B-Mode or Power Doppler signal with ultrasound at one of the 76/78 joints of flexor/extensor tendons of hand or feet
4. 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
5. Genetics: HLA status with positive risk allele for RA such as HLA DRB1*01,*02,*03,*04...*015
6. Non-pregnant, non-breastfeeding female patients

Exclusion criteria 10

1. Clinically apparent arthritis (76/78 joint count)
2. Fulfilment of ACR/EULAR 2010 Classification Criteria for RA
3. Any previous therapy with bDMARD/tsDMARD/cDMARD
4. Any malignancy risk factor (e.g. current malignancy or history of malignancy)
5. Any active, chronic or recurrent infection
6. Any uncontrolled comorbidity
7. Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process, obtained within 3 months or according to local guidelines prior to screening and evaluated by a qualified physician
8. Contraindication for baricitinib treatment according to its SmPC
9. 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)
10. Any known VTE risk factor (e.g. previous VTE/LE or inherited coagulation disorder)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of patients with development of arthritis at week 48

Secondary endpoints 6

1. Number of patients with development of arthritis at week 24
2. Fulfillment of the ACR/EULAR 2010 RA classification criteria
3. Ultrasound: number of patients without signs of PD synovitis or PD tenosynovitis at week 24 and week 48 compared to baseline and compared within both groups
4. Safety: (S)AE
5. Subjective (SACRAH, sMHQ) and objective (moberg pick up test (MPUT)) hand function
6. Change in anti CCP2 antibody levels (RE/ml)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Erlangen AöR

Sponsor organisation

Universitaetsklinikum Erlangen AöR

Address

Maximiliansplatz 2, Innenstadt Innenstadt

City

Erlangen

Postcode

91054

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Erlangen AöR

Contact name

Sara Bayat

Public contact point

Organisation

Universitaetsklinikum Erlangen AöR

Contact name

Sara Bayat

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 2 files

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

Application history

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