CIZUTAMIG for Primary Sjögren's syndrome | Idiopathic inflammatory myopathy | Systemic sclerosis | Rheumatoid arthritis

Inclusion criteria

• {"criterion_text":"- Written informed consent and data protection declaration obtained prior to the initiation of any protocol required procedures\n- Disease specific inclusion criteria (RA): a.\tFulfilment of the 2010 ACR/EULAR classification criteria for RA b.\tRheumatoid factor (RF) and/or ACPA positivity at screening c.\tDisease Activity Score DAS28-CRP>3.2 at screening d.\tTender joint count (TJC) ≥ 3/68 and swollen joint count (SJC) ≥ 3/66 at screening e.\tFailure (defined as inadequate response after at least 3 months of therapy or intolerance) of at least one conventional DMARD and at least two tsDMARD/bDMARDs with different mechanisms\n- Willing and able to comply to study procedures and study protocol\n- Age ≥ 18 years at time of consent\n- Male participants unless surgically sterile, must agree to use two acceptable methods for contraception (e.g. spermicide and condom) during the trial and refrain from fathering a child starting from the time of signing the Informed Consent Form (ICF) throughout the trial\n- Females of childbearing potential (FCBP) must have a negative serum pregnancy test at screening and must agree to use a highly effective contraceptive method (Pearl index <1) starting from the time of signing the ICF and throughout the trial. If they take oral contraceptives, the patients must also agree to use two other acceptable methods for contraception (e.g. spermicide and condom) during the trial.\n- Updated vaccination record according to the Standing Committee on Vaccination (STIKO) recommendations for immunocompromised patients\n- Disease specific inclusion criteria (SSC): a.\tFulfillment of the 2013 ACR/EULAR classification criteria for SSc b.\tPositivity for at least one SSc-specific or associated antibody c.\tDiffuse cutaneous disease d.\tSevere disease defined as at least one of the following: i.\tSkin disease with screening mRSS ≥ 10 AND skin disease progression by ≥ 3 mRSS points or involvement of 1 new body area, or mRSS increase ≥ 2 units in 1 body area within the last 6 months and/or new tendon friction rubs ii.\tSSc-associated interstitial lung disease with either reduction of FVC of ≥ 5% and/or reduction of DLCO of ≥ 10% within the last 12 months before screening and/or presence of ILD with signs of alveolitis on HRCT with FVC < 85% iii.\tSSc-associated cardiac involvement with Troponin T elevation e.\tFailure (defined as inadequate response after at least 3 months of therapy or intolerance) of at least two of the following treatments with different mechanisms: glucocorticoids, methotrexate, azathioprine, mycophenolate mofetil, tocilizumab, rituximab, cyclophosphamide, tacrolimus, cyclosporine, nintedanib, hydroxychloroquine\n- Disease specific inclusion criteria (IIM): a.\tDiagnosis of IIMs including DM, PM (including antibody-positive immune-mediated necrotizing myopathy [IMNM]), anti-synthetase syndrome according to the 2017 American College of Rheumatology [ACR]/European Alliance of Associations for Rheumatology [EULAR] classification criteria (including probable or definite diagnosis; > 55%) b.\tPositivity for at least one myositis specific or associated antibody c.\tSevere, active disease defined as at least one of the following: i.\tMyositis with •\tRecent (within the last 6 months) evidence of myositis in muscle biopsy and/or muscle MRI and/or EMG and/or PET/CT •\tAND/OR at least two of the following: Manual Muscle Testing-8 (MMT-8) score ≤142; extra-muscular activity ≥2 cm; health Assessment Questionnaire ≥0.25; at least one muscle enzyme >1.5 times upper limit of normal; VAS of patient global assessment ≥ 2 cm; VAS of physician global assessment ≥ 2cm ii.\tIIM-associated interstitial lung disease with reduction of FVC of ≥ 5% and/or reduction of DLCO of ≥ 10% within the last 12 months and/or presence of ILD with signs of alveolitis on HRCT with FVC < 85% d.\tFailure (defined as inadequate response after at least 3 months of therapy or intolerance) of at least two of the following treatments with different mechanisms: glucocorticoids, methotrexate, azathioprine, mycophenolate mofetil, rituximab, cyclophosphamide, intravenous immunoglobulins, tacrolimus, cyclosporin A, nintedanib, janus kinase inhibitors, hydroxychloroquine\n- Disease specific inclusion criteria (pSjD): a.\tFulfillment of the 2016 ACR/EULAR classification criteria for SjD b.\tPositivity for SSA antibodies in serum c.\tModerate to severe disease defined as ESSDAI and/or ESSPRI ≥ 5 d.\tFailure (defined as inadequate response after at least 3 months of therapy or intolerance) of at least two of the following treatments with different mechanisms: glucocorticoids, hydroxychloroquine, methotrexate, azathioprine, leflunomide, rituximab, abatacept, belimumab, tacrolimus, cyclosporine A, mycophenolate mofetil, cyclophosphamide, intravenous immunoglobulins."}

Exclusion criteria

• {"criterion_text":"- ANC < 500/µl, hemoglobin < 6/dl, absolute CD3+T cell count < 500/µl at screening\n- Life-threatening allergies, hypersensitivity, or intolerance to cizutamig or its excipients or tocilizumab\n- Pregnancy or lactation\n- Females who are intending to conceive during the study\n- Malignancy in the last 5 years before screening (except basal or squamous cell skin cancer)\n- Requirement for immunization with live vaccine during the study period\n- Participants who are younger than 18 years or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent\n- Participants who have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the Investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results\n- Participants who possibly are dependent on the sponsor, the Principal Investigator or Investigator (e.g. family members)\n- Patients who are institutionalized by court order or regulatory action\n- Subjects participating in another clinical trial with an investigational medicinal product or medical device (there must be at least 3 months since the last IMP administration before this trial)\n- Severely impaired liver (Child Pugh C), cardiac or pulmonory (NYHA IV) function and need for supplemental oxygen\n- Patients with known selective IgA deficiency\n- IgG level below 4g/l at screening\n- Any condition, including the presence of laboratory abnormalities, which places the participants at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study, including active infections and within 1 week of completing anti-infective treatment, neurologic conditions, primary immunodeficiency and history of splenectomy\n- Patients will be excluded if they are known to have any of the following: a.\tSevere infection requiring hospitalization within the last two weeks. b.\tAny known human immunodeficiency virus (HIV) infection or positive HIV-1 or -2 antibody at screening c.\tPositive hepatitis B surface antigen (HBsAg). Patients with positive hepatitis B core antibody (HBcAb) must be tested for hepatitis B virus (HBV)-DNA to determine their status; if HBV DNA is positive, patients should be excluded; if HBV-DNA is negative, the patient may participate in the study. d.\tPatients with positive hepatitis C virus (HCV) antibody must be tested for HCV ribonucleic acid (RNA); if HCV RNA is also positive, patients should be excluded; if HCV RNA is negative, the patient may participate in the study at the investigator’s discretion. e.\tActive tuberculosis (TB) or lack of documentation of completion of treatment for active TB. If the TB test (QuantiFERON® Gold Test) is positive, patients may be allowed to enroll if chest CT is negative for active TB and treatment according to local guidelines has been initiated or completed prior to enrollment. If the TB test result is indeterminate, the site should repeat the test. A positive test result or 2 successive indeterminate results should be considered as a positive result. An indeterminate test result followed by a negative test result should be considered as a negative test result.\n- Receipt of or inability to discontinue any of the following excluded therapies at screening: a.\tAnti-metabolites: MMF/mycophenolate sodium, azathioprine, methotrexate b.\tCalcineurin inhibitors: e.g., but not limited to cyclosporine, tacrolimus, voclosporin c.\tAlkylating agent: cyclophosphamide d.\tJanus kinase (JAK) inhibitors, Bruton tyrosine kinase (BTK) inhibitors, Tyrosine kinase 2 (TYK2) inhibitors: e.g., but not limited to tofacitinib, upadacitinib, baricitinib, deucravacitinib e.\tComplement inhibitors: e.g., but not limited to eculizumab, ravulizumab, zilucoplan, avacopan f.\tPlasmapheresis or intravenous immunoglobulin (IVIg) g.\tFcRn inhibitors: including but not limited to efartigimod, rozanolixizumab h.\tAny of the following (including biosimilars): Tumor necrosis factor (TNF) inhibitors: e.g., but not limited to infliximab, adalimumab or anti-cytokine (IL-1, IL-6, IL-17, IL-12/23): e.g., but not limited to anakinra, tocilizumab, secukinumab, ustekinumab, risankizumab i.\tAnti-B-cell activating factor (BAFF) or anti-a proliferation inducing ligand (APRIL): e.g., but not limited to belimumab, telitacicept j.\tThalidomide or thalidomide derivatives k.\tCD19 inhibitor: e.g., but not limited to inebilizumab l.\tCD20 inhibitors: e.g., but not limited to rituximab, ocrelizumab, obinutuzumab m.\tOther cell depleting therapy, anti-CD3, anti-CD4, anti-CD5\n- Prior chimeric antigen receptor (CAR)-T or TCE therapy directed at any antigen or BCMA-targeted therapy at any time\n- Inability to taper glucocorticoids to a maximun of 20mg prednisolone equivalent per day until enrolment"}

Primary endpoints

• {"endpoint_text":"- Primary endpoint (Safety): Incidence and grading of severity of Cytokine Release Syndrome (CRS), Immune Cell Associated Neurotoxicity Syndrome (ICANS) and treatment-emergent adverse events (TEAE) and serious adverse events (SAE) due to IMP until 28 days after the last administration of BCMAxCD3 TCE cizutamig","definition_or_measurement_approach":"Incidence and grading of CRS, ICANS, TEAEs and SAEs attributed to the investigational medicinal product, assessed and graded until 28 days after the last administration of BCMAxCD3 TCE cizutamig."}

Secondary endpoints

• {"endpoint_text":"- Main disease specific clinical efficacy (SSc): rCRISS30/5 response at Week 16","definition_or_measurement_approach":"rCRISS30/5 response assessed at Week 16"}
• {"endpoint_text":"- Main disease specific clinical efficacy (IIM): moderate or major total improvement score (TIS) response at week 16","definition_or_measurement_approach":"Moderate or major TIS response assessed at Week 16"}
• {"endpoint_text":"- Main disease specific clinical efficacy (pSjD): change from baseline in European Alliance of Associations for Rheumatology (EULAR) Sjögren's syndrome disease activity index (ESSDAI) at week 16","definition_or_measurement_approach":"Change from baseline in ESSDAI measured at Week 16"}
• {"endpoint_text":"- Main disease specific clinical efficacy (RA): American College of Rheumatology (ACR) 20 response at week 16","definition_or_measurement_approach":"ACR20 response assessed at Week 16"}
• {"endpoint_text":"- Main disease specific clinical efficacy (ONLY for those with interstitial lung disease [ILD] at baseline for all IMIDs): Change in forced vital capacity (FVC) and diffusion capacity of the lungs for carbon monoxide (DLCO) at 16 and 52 weeks compared to baseline","definition_or_measurement_approach":"Change in FVC and DLCO measured at Weeks 16 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (SSc): rCRISS 20/30/50 response at week 16 and 52","definition_or_measurement_approach":"rCRISS 20/30/50 responses assessed at Weeks 16 and 52"}
• {"endpoint_text":"- Further disease specific clinical efficacy (SSc): Change in modified Rodnan skin score (mRSS) at 16, 24 and 52 weeks compared to baseline","definition_or_measurement_approach":"Change in mRSS measured at Weeks 16, 24 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (SSc): Change in Troponin T levels at 16, 24 and 52 weeks compared to baseline","definition_or_measurement_approach":"Change in Troponin T levels at Weeks 16, 24 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (SSc): Change in EULAR SSc Impact Score (Sclero-ID) over time compared to baseline","definition_or_measurement_approach":"Change in Sclero-ID assessed over time versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (SSc): Change in digital ulcer count at 16, 24 and 52 weeks compared to baseline","definition_or_measurement_approach":"Change in digital ulcer count measured at Weeks 16, 24 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (IIM): Minimal, moderate or major TIS response at 16, 24 and 52 weeks","definition_or_measurement_approach":"TIS response categories (minimal/moderate/major) assessed at Weeks 16, 24 and 52"}
• {"endpoint_text":"- Further disease specific clinical efficacy (IIM): Change in TIS score from baseline at 16, 24 and 52 weeks","definition_or_measurement_approach":"Change in TIS score measured at Weeks 16, 24 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (IIM): Change in muscle memory test 8 (MMT8) at 16, 24 and 52 weeks compared to baseline","definition_or_measurement_approach":"Change in MMT8 measured at Weeks 16, 24 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (IIM): Change in physician’s global assessment of extramuscular activity at 16, 24 and 52 weeks compared to baseline","definition_or_measurement_approach":"Change in physician's global assessment measured at Weeks 16, 24 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (IIM): Change in cutaneous disease area and severity index (CDASI) at 16, 24 and 52 weeks (in case of DM) compared to baseline","definition_or_measurement_approach":"Change in CDASI (for DM) measured at Weeks 16, 24 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (IIM): Change in CK, aldolase and Troponin T levels over time compared to baseline","definition_or_measurement_approach":"Change in CK, aldolase and Troponin T measured over time versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (pSjD): Change from baseline in ESSDAI at week 24 and 52","definition_or_measurement_approach":"Change in ESSDAI measured at Weeks 24 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (pSjD): Change from baseline in EULAR Sjögren’s syndrome patient reported index (ESSPRI) at week 16, 24 and 52","definition_or_measurement_approach":"Change in ESSPRI measured at Weeks 16, 24 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (pSjD): Percentage (%) of participants with decrease in ESSPRI ≥1 or 15% from baseline at 16, 24 and 52 weeks","definition_or_measurement_approach":"Proportion of participants with ESSPRI decrease ≥1 point or ≥15% from baseline at Weeks 16, 24 and 52"}
• {"endpoint_text":"- Further disease specific clinical efficacy (pSjD): Percentage (%) of participants with decrease in ESSDAI ≥3 points from baseline at 16, 24 and 52 weeks","definition_or_measurement_approach":"Proportion of participants with ESSDAI decrease ≥3 points at Weeks 16, 24 and 52"}
• {"endpoint_text":"- Further disease specific clinical efficacy (pSjD): Percentage (%) of participants with ESSDAI <5 at 16, 24 and 52 weeks","definition_or_measurement_approach":"Proportion of participants with ESSDAI <5 at Weeks 16, 24 and 52"}
• {"endpoint_text":"- Further disease specific clinical efficacy (pSjD): Change from baseline in oral and ocular dryness numerical rating scale (NRS) at 16 and 52 weeks","definition_or_measurement_approach":"Change in oral and ocular dryness NRS at Weeks 16 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (pSjD): Percentage (%) of participants with increase of Schirmer's test ≥ 5 mm if abnormal baseline at 16 and 52 weeks","definition_or_measurement_approach":"Proportion with Schirmer's test increase ≥5 mm (if abnormal baseline) at Weeks 16 and 52"}
• {"endpoint_text":"- Further disease specific clinical efficacy (RA): American College of Rheumatology (ACR) 50/70 response at 16, 24 and 52 weeks.","definition_or_measurement_approach":"ACR50/70 responses assessed at Weeks 16, 24 and 52"}
• {"endpoint_text":"- Further disease specific clinical efficacy (RA): ACR 20 response at week 24 and 52 weeks.","definition_or_measurement_approach":"ACR20 response assessed at Weeks 24 and 52"}
• {"endpoint_text":"- Further disease specific clinical efficacy (RA): Disease acitivity score 28 (DAS28)-CRP / DAS28-ESR / simplified disease acitivity index (SDAI) / Boolean remission at 16, 24, and 52 weeks.","definition_or_measurement_approach":"DAS28-CRP/DAS28-ESR/SDAI/Boolean remission assessed at Weeks 16, 24 and 52"}
• {"endpoint_text":"- Further disease specific clinical efficacy (RA): Proportion of patients with DAS28-CRP<3.2 at week 16, 24 and 52","definition_or_measurement_approach":"Proportion with DAS28-CRP <3.2 at Weeks 16, 24 and 52"}
• {"endpoint_text":"- Further disease specific clinical efficacy (RA): Change in DAS28-CRP / SDAI / clinical disease activity index (CDAI) at 16, 24, and 52 weeks compared to baseline.","definition_or_measurement_approach":"Change in DAS28-CRP/SDAI/CDAI at Weeks 16, 24 and 52 versus baseline"}
• {"endpoint_text":"- Further disease specific clinical efficacy (RA): Change in ESR values over time compared to baseline","definition_or_measurement_approach":"Change in ESR measured over time versus baseline"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Duration without disease-modifying antirheumatic drug (DMARD) therapy from week 5 to week 52","definition_or_measurement_approach":"Duration without DMARD therapy measured from Week 5 to Week 52"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Time until clinical relapse or flare observed between week 5 and week 52","definition_or_measurement_approach":"Time to clinical relapse/flare between Weeks 5 and 52"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Number of flares from week 5 through week 52","definition_or_measurement_approach":"Number of disease flares recorded from Week 5 through Week 52"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Cumulative steroid dosage from week 5 to week 52","definition_or_measurement_approach":"Cumulative steroid dose from Week 5 to Week 52"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Change in levels of CRP over time compared to baseline","definition_or_measurement_approach":"Change in CRP levels over time versus baseline"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Change in hand strength over time compared to baseline","definition_or_measurement_approach":"Change in hand strength over time versus baseline"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Change in patient’s global assessment (PtGA) of disease activity (VAS 0-100mm) over time compared to baseline","definition_or_measurement_approach":"Change in PtGA (VAS 0-100mm) over time versus baseline"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Change in physician’s global assessment (PhGA) of disease activity (VAS 0-100mm) over time compared to baseline","definition_or_measurement_approach":"Change in PhGA (VAS 0-100mm) over time versus baseline"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Change in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) over time compared to baseline","definition_or_measurement_approach":"Change in FACIT-F scores over time versus baseline"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Change in Short Form 36 (SF-36, quality of life questionnaire) over time compared to baseline","definition_or_measurement_approach":"Change in SF-36 scores over time versus baseline"}
• {"endpoint_text":"- General clinical response and patient reported outcomes in all IMID groups: Change in Health Assessment Questionnaire Disability Index (HAQ-DI) over time compared to baseline","definition_or_measurement_approach":"Change in HAQ-DI over time versus baseline"}

Germany

Earliest CTIS Part Ii Submission Date

17-11-2025

Latest Decision Or Authorization Date

28-11-2025

Processing Time Days

11

Number Of Sites

1

Number Of Participants

12

Primary sponsor

Full Name

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Candid Therapeutics","duties_or_roles":"Source of monetary support","organisation_type":""}