Baricitinib in CPPD - the BAPTIST Study

NCT06768294 | Not Yet Recruiting Phase 2

• 1 other identifier: Baptist (L4194)
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this clinical trial is to determine if baricitinib is effective in treating calcium pyrophosphate deposition disease (CPPD) in adults. The primary objective is to assess its impact on joint inflammation. The key questions the study seeks to answer are:

• Can baricitinib reduce inflammation in affected joints?
• Will baricitinib lead to changes in ultrasound findings, such as calcium crystal deposition and synovitis? Researchers will compare baricitinib to other treatments, including methylprednisolone, colchicine, hydroxychloroquine, and methotrexate with folic acid, for managing CPPD.

Conditions

Calcium Pyrophosphate Deposition Disease; Chondrocalcinosis

Keywords

calcium pyrophosphate deposition disease; chondrocalcinosis; pseudogout; ultrasound; baricitinib; olumiant; synovial biopsy; arthritis

Outcome Measures

Primary Outcomes (1)

• The evaluation the effect of baricitinib on inflammation of the synovial membrane in CPPD

  CD68 score will be used as outcome measure for the primary objective. CD68 score will be calculated from an analysis of 6 images from each biopsy section and expressed as the mean area of tissue occupied by positively stained cells.

  The outcome for the primary objective is the changes in the synovial tissue CD68 scoring at 12 weeks, an objective outcome measure.

Secondary Outcomes (13)

• To assess the changes in Krenn synovitis score at the synovial level

  12 weeks

• To assess the changes in cytochin levels at the synovial membrane

  12 weeks

• To determine changes at ultrasound examination in terms of calcium crystal deposition

  4, 12 and 24 weeks

• To determine changes at ultrasound examination in terms of synovitis

  4, 12 and 24 weeks

• To determine changes at ultrasound examination in terms of bone changes

  4, 12 and 24 weeks

Other Outcomes (1)

• To explore the possible baricitinib-induced impact on whole-body metabolism

  24 weeks

Study Arms (2)

One group will receive baricitinib at the dose of 4mg/daily

ACTIVE COMPARATOR

Drug: Baricitinib 4 MG Oral Tablet

standard of care (to be decided according to the guidelines)

SHAM COMPARATOR

Methylprednisolone tablets, Colchicine 1 mg tablets, Hydroxychloroquine 200 mg tablets, MTX + folic acid (to be decided according to the guidelines)

Drug: Methylprednisolone (Corticosteroid); Drug: Colchicine 1 MG Oral Tablet; Drug: Hydroxychloroquine 200 mg; Combination Product: Methotrexate + Folic Acid

Interventions

Baricitinib 4 MG Oral Tablet DRUG

Baricitinib is a JAK1/JAK2 inhibitor approved for use in Rheumatoid Arthritis. It is under investigation for use in several inflammatory diseases, including Psoriasis and Psoriatic Arthritis, Atopic Dermatitis, Inflammatory Bowel Disease and Systemic Lupus Erythematosus, with encouraging results. As IL-6 plays a central role in CPPD inflammatory process, a broad spectrum of interleukins and other proinflammatory proteins (including interferons) could be involved. A drug that acts by blocking more than one proinflammatory cytokine could be a promising treatment for a multifaceted disease such as CPPD.

One group will receive baricitinib at the dose of 4mg/daily

Methylprednisolone (Corticosteroid) DRUG

The initial dosage of methylprednisolone may vary depending on the entity of inflammation and the patient's comorbidities. Usually in CPPD a short-term administration of methylprednisolone starts with 16 mg per day after breakfast decreasing the initial dosage in small decrements at appropriate time intervals until discontinuation, in about 2 weeks. Methylprednisolone will be given in combination with gastroprotective agents such as proton pump inhibitors.

standard of care (to be decided according to the guidelines)

Colchicine 1 MG Oral Tablet DRUG

1 or ½ tablet (depending on individual tolerance) daily after breakfast

standard of care (to be decided according to the guidelines)

Hydroxychloroquine 200 mg DRUG

1 tablet daily after lunch

standard of care (to be decided according to the guidelines)

Methotrexate + Folic Acid COMBINATION_PRODUCT

MTX 2.5 mg tablets, from 2 to 4 tablets (5-10mg), depending on disease severity, to be administered once weekly after dinner, always in the same day of the week. One tablet of folic acid (folina 5 mg) will be administered the day after MTX administration, after breakfast, to reduce and prevent the common side effects of MTX.

standard of care (to be decided according to the guidelines)

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent;
• Male and female patients aged ≥55 years;
• Patients that according to the investigator's judgement will benefit from the proposed treatments (favourable benefit/risk profile)
• Menopause for women;(no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a high follicle stimulating single measurement is insufficient.);
• Male patients must avoid having a child during the trial and must use one of the highly effective methods of contraception or sexual abstinence or have a menopause partner (no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a high follicle stimulating single measurement is insufficient). Contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Sterilization of the female partner (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before the partner enrollment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment
• Male sterilization (vasectomy) at least 6 months prior to screening
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps).
• The female partner use oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS)
• Patients fulfilling the 2023 ACR/EULAR classification criteria for CPPD disease;
• Patients with feasibility of synovial biopsy at the knee or wrist joint;
• Patients with CPPD clinical presentation that may be:
• Subset 2: patients with prevalent involvement of the large joints (oligoarthritis). Patients with recurrent/persistent effusion in one or more large joints (independently of the presence and grade of OA), not responsive to a single injection of steroid and white cell count in joint synovial fluid that is more than 2000 cells/mm3 and/or patients with acute monoarticular arthritis, with more than 3 attacks in one joint in the last 12 months, will be included in this group.

You may not qualify if:

• Patients positive at anticitrullinated positive antibodies (ACPA), any titre;
• Patients affected by seronegative arthritis or other conditions that may be responsible of arthritis (i.e. gout, rheumatic polymyalgia, etc);
• Patients that refuse synovial biopsy or present contraindications, according to investigator's judgement, including (but not limited to) increased risk for bleeding (platelet count \<100000 or use of anticoagulants), allergy to local anesthetics, suspicion of septic arthritis;
• Patients with history of malignancy or lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for \< 5 years;
• Patients with cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinomas who have had active disease within 3 years of screening for this study;
• Patients with active, untreated, acute or chronic infection (such as untreated tuberculosis), or immunocompromised to an extent that such that participation in the study would pose an unacceptable risk to the subject. Patients with treated infections such as latent tuberculosis after completion of the appropriate therapy are not excluded;
• Patients with clinically serious infection or that have received intravenous antibiotics for an infection, within 4 weeks of randomization;
• Patients with active viral infection that, based on the investigator\'s clinical assessment, makes the patient an unsuitable candidate for the study;
• Patients with serology suggestive for active or chronic hepatitis B or hepatitis C infection; anti-HCV, anti-HBs, anti-HBc antibodies and HBcAg, HBsAg will be tested. Patients that will result positive for anti-HCV and/or HBcAg and/or HBsAg and/or anti-HBc antibodies will be excluded from the study. Patients who are positive for both anti-HBc and antiHBs, but negative for HBcAg and HBsAb could be enrolled.
• Patients with symptomatic herpes zoster infection within 12 weeks of screening or recurrent or disseminated (even a single episode) herpes zoster;
• Patients with a history of disseminated opportunistic infections (e.g., listeriosis and histoplasmosis);
• Patients with a history of venous thromboembolism (VTE), or are considered at high risk for VTE as deemed by the investigator
• Patients who are currently on immunosuppressive therapies or have not discontinued them for at least 4 weeks;
• Patients with clinically significant (per investigator\'s judgement) drug or alcohol abuse within the last 6 months preceding the baseline visit;
• Patients with any major surgery within 8 weeks prior to baseline or requiring major surgery during the study, which in the opinion of the investigator would pose an unacceptable risk to the patient;

Sponsors & Collaborators

• I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio: lead

Study Sites (1)

IRCCS Galeazzi - Sant Ambrogio Hospital

Milan, 20157, Italy

Location

Related Publications (19)

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• Sirotti S, Terslev L, Filippucci E, Iagnocco A, Moller I, Naredo E, Vreju FA, Adinolfi A, Becce F, Hammer HB, Cazenave T, Cipolletta E, Christiansen SN, Delle Sedie A, Diaz M, Figus F, Mandl P, MacCarter D, Mortada MA, Mouterde G, Porta F, Reginato AM, Schmidt WA, Serban T, Wakefield RJ, Zufferey P, Sarzi-Puttini P, Zanetti A, Damiani A, Pineda C, Keen HI, D'Agostino MA, Filippou G; OMERACT Ultrasound working group-CPPD subgroup. Development and validation of an OMERACT ultrasound scoring system for the extent of calcium pyrophosphate crystal deposition at the joint level and patient level. Lancet Rheumatol. 2023 Aug;5(8):e474-e482. doi: 10.1016/S2665-9913(23)00136-4. Epub 2023 Jul 5.

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• Terslev L, Naredo E, Aegerter P, Wakefield RJ, Backhaus M, Balint P, Bruyn GAW, Iagnocco A, Jousse-Joulin S, Schmidt WA, Szkudlarek M, Conaghan PG, Filippucci E, D'Agostino MA. Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 2: reliability and application to multiple joints of a standardised consensus-based scoring system. RMD Open. 2017 Jul 11;3(1):e000427. doi: 10.1136/rmdopen-2016-000427. eCollection 2017.

  PMID: 28948984 BACKGROUND

• Uson J, Rodriguez-Garcia SC, Castellanos-Moreira R, O'Neill TW, Doherty M, Boesen M, Pandit H, Moller Parera I, Vardanyan V, Terslev L, Kampen WU, D'Agostino MA, Berenbaum F, Nikiphorou E, Pitsillidou IA, de la Torre-Aboki J, Carmona L, Naredo E. EULAR recommendations for intra-articular therapies. Ann Rheum Dis. 2021 Oct;80(10):1299-1305. doi: 10.1136/annrheumdis-2021-220266. Epub 2021 May 25.

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• Genovese MC, Smolen JS, Takeuchi T, Burmester G, Brinker D, Rooney TP, Zhong J, Daojun M, Saifan C, Cardoso A, Issa M, Wu WS, Winthrop KL. Safety profile of baricitinib for the treatment of rheumatoid arthritis over a median of 3 years of treatment: an updated integrated safety analysis. Lancet Rheumatol. 2020 Jun;2(6):e347-e357. doi: 10.1016/S2665-9913(20)30032-1.

  PMID: 38273598 BACKGROUND

• Caporali R, Taylor PC, Aletaha D, Sanmarti R, Takeuchi T, Mo D, Haladyj E, Bello N, Zaremba-Pechmann L, Fang Y, Dougados M. Efficacy of baricitinib in patients with moderate-to-severe rheumatoid arthritis up to 6.5 years of treatment: results of a long-term study. Rheumatology (Oxford). 2024 Oct 1;63(10):2799-2809. doi: 10.1093/rheumatology/keae012.

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• Filippou G, Adinolfi A, Cimmino MA, Scire CA, Carta S, Lorenzini S, Santoro P, Sconfienza LM, Bertoldi I, Picerno V, Di Sabatino V, Ferrata P, Galeazzi M, Frediani B. Diagnostic accuracy of ultrasound, conventional radiography and synovial fluid analysis in the diagnosis of calcium pyrophosphate dihydrate crystal deposition disease. Clin Exp Rheumatol. 2016 Mar-Apr;34(2):254-60. Epub 2016 Feb 9.

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• Abhishek A, Tedeschi SK, Pascart T, Latourte A, Dalbeth N, Neogi T, Fuller A, Rosenthal A, Becce F, Bardin T, Ea HK, Filippou G, Fitzgerald J, Iagnocco A, Liote F, McCarthy GM, Ramonda R, Richette P, Sivera F, Andres M, Cipolletta E, Doherty M, Pascual E, Perez-Ruiz F, So A, Jansen TL, Kohler MJ, Stamp LK, Yinh J, Adinolfi A, Arad U, Aung T, Benillouche E, Bortoluzzi A, Dau J, Maningding E, Fang MA, Figus FA, Filippucci E, Haslett J, Janssen M, Kaldas M, Kimoto M, Leamy K, Navarro GM, Sarzi-Puttini P, Scire C, Silvagni E, Sirotti S, Stack JR, Truong L, Xie C, Yokose C, Hendry AM, Terkeltaub R, Taylor WJ, Choi HK. The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease. Ann Rheum Dis. 2023 Oct;82(10):1248-1257. doi: 10.1136/ard-2023-224575. Epub 2023 Jul 26.

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MeSH Terms

Conditions

Chondrocalcinosis; Arthritis

Interventions

baricitinib; Methylprednisolone; Adrenal Cortex Hormones; Colchicine; Hydroxychloroquine; Methotrexate; Folic Acid

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Alkaloids; Heterocyclic Compounds; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines

Study Officials

• Georgios Filippou, Assistant Professor

  IRCCS Galeazzi - Sant'Ambrogio Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Georgios Filippou, Assistant professor

CONTACT

0039 0283502707; georgios.filippou@grupposandonato.it

Silvia Sirotti, researcher

CONTACT

0039 028350270; silvia.sirotti@grupposandonato.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2024
• First Posted: January 10, 2025
• Study Start: January 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 10, 2025

Record last verified: 2025-01

Locations

IT (1)