“The BAPTIST study” Baricitinib in calcium pyrophosphAte dePosiTion dIseaSe Trial – a proof of concept phase II clinical trial .

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ospedale Galeazzi S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

8 Jan 2025 → ongoing

Decision date (initial)

2024-09-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Eli Lilly Italia S.p.A and I.R.C.C.S. Ospedale Galeazzi - Sant’Ambrogio

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the effect of Baricitinib on inflammation of the synovial membrane in CPPD. The outcome for the primary objective is the changes in the synovial tissue CD68 scoring at 12 weeks, an objective outcome measure.

Secondary objectives 7

1. To assess changes in Krenn synovitis score and cytokines at the synovial level
2. To evaluate the improvement of patient-reported outcomes (PROs) and pain.
3. To determine changes at ultrasound examination in terms of calcium crystal deposition, synovitis and degenerative changes.
4. To identify subsets of the disease that could have a better response to the treatment.
5. to evaluate the effect of baricitinib on serum cytokine levels at a plasmatic level.
6. To explore the possible baricitinib-induced impact on whole-body metabolism.
7. To explore differences in biochemical and immunohistological markers between patients with the acute and the chronic form of CPPD.

Conditions and MedDRA coding

calcium pyrophosphate deposition disease

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed Informed Consent
2. Male and female patients aged ≥55 years
3. 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 accordingly to the Contraception Guidance Version_1.2_March_2024). HMA/03-Working_Groups/CTCG/2024_HMA_CTCG_Contraception_guidance_Version_1.2March_2024.
4. 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)
5. Patients fulfilling the 2023 ACR/EULAR classification criteria for CPPD disease
6. Patients with feasibility of synovial biopsy at the knee or wrist joint
7. Patients with CPPD clinical presentation that may be: -Subset 1: patients with prevalent polyarticular involvement of the small joints and tendons of hands and wrists (rheumatoid-like subset). Patients that present with prevalent inflammatory involvement of the hands and wrists (joints and/or tendons), with or without acute attacks of arthritis of the large joints, will be included in this group. Inclusion criteria will be joint effusion and/or synovitis of the II and/or III metacarpal phalangeal (MCP) joint of at least one hand, tenosynovitis of at least 1 tendon of one hand or wrist, hyperostosis of the II and/or III MCP head; -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.
8. Patients that according to the investigator’s judgement will benefit from the proposed treatments (favourable benefit/risk profile)

Exclusion criteria 21

1. Patients positive at anticitrullinated positive antibodies (ACPA), any titre
2. Patients with presence of significant uncontrolled respiratory, hepatic, renal, endocrine, hematologic, neurologic, or neuropsychiatric disorders, or abnormal laboratory screening values that, in the opinion of the investigator, pose an unacceptable risk to the patient if participating in the study or of interfering with the interpretation of the data
3. Patients with clinical laboratory test results at screening that are outside the normal reference range of the population and are considered clinically significant, or have any of the following specific abnormalities: neutrophil count <1500 cells/µL, lymphocyte count <500 cells/µL, platelet count <100,000 cells/µL, aspartate transaminase (AST) or alanine aminotransferase (ALT) > 2 times the upper limit of normal, haemoglobin <10 g/dL for male and female subjects, eGFR <30 mL/min
4. Patients affected by seronegative arthritis or other conditions that may be responsible of arthritis (i.e. gout, rheumatic polymyalgia, etc)
5. Patients with any other condition that precludes him/her from following and completing the protocol, in the opinion of the investigator
6. Patients currently enrolled in or discontinued from a clinical trial involving an investigational product or non-approved use of a drug or device within the last 4 weeks or a period of at least 5 half-lives of the last administration of the drug, whichever is longer, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
7. 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
8. 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
9. 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
10. 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
11. Patients with clinically serious infection or that have received intravenous antibiotics for an infection, within 4 weeks of randomization
12. Patients with symptomatic herpes zoster infection within 12 weeks of screening or recurrent or disseminated (even a single episode) herpes zoster
13. Patients with active viral infection that, based on the investigator's clinical assessment, makes the patient an unsuitable candidate for the study
14. 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 anti-HBs, but negative for HBcAg and HBsAb could be enrolled.
15. Hypersensitivity to the active substance or to any of the excipients
16. Patients with a history of disseminated opportunistic infections (e.g., listeriosis and histoplasmosis)
17. Patients with a history of venous thromboembolism (VTE), or are considered at high risk for VTE as deemed by the investigator
18. Patients who are currently on immunosuppressive therapies or have not discontinued them for at least 4 weeks
19. Patients with clinically significant (per investigator's judgement) drug or alcohol abuse within the last 6 months preceding the baseline visit
20. 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
21. Patients with recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting and uncontrolled hypertension (confirmed systolic blood pressure >160 mmHg or diastolic blood pressure >100 mm Hg); patients with less recent major cardiovascular events (> 6 months) will be thoroughly assessed for cardiovascular risk taking under consideration all possible risk factors and the disease phenotype and activity and will be included only in case of favourable benefit/risk ratio according to the principal investigators judgement.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in CD68 at 12 weeks.

Secondary endpoints 6

1. Change from baseline in Krenn synovitis score at 12 weeks
2. Change from baseline in CD3, CD8, CD20 at synovial level at 12 weeks
3. Change from baseline in DAS, HAQ score and WOMAC at 4, 12 and 24 weeks.
4. Change from baseline in MSUS EULAR-OMERACT synovitis score at 4, 12 and 24 weeks, CPP deposition extent according to the OMERACT CPPD scoring system at 4, 12 and 24 weeks and degenerative changes at 4, 12 and 24 weeks.
5. Change from baseline in serum cytokines levels (IL-1, IL-6, IL-8, anti-TNFα, Interferon α and γ, TGF-β) at 12 and 24 weeks
6. Change from baseline in visual analogic scale (VAS) pain at 4, 12 and 24 weeks

Investigational products

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

Test 1

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ospedale Galeazzi S.p.A.

Sponsor organisation

Ospedale Galeazzi S.p.A.

Address

Via Cristina Belgioioso 173

City

Milan

Postcode

20157

Country

Italy

Scientific contact point

Organisation

Ospedale Galeazzi S.p.A.

Contact name

Rheumatology Unit

Public contact point

Organisation

Ospedale Galeazzi S.p.A.

Contact name

Rheumatology Unit

Third parties 4

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 22 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