CND261 for ANCA-associated vasculitis (ANCA-IgG-positive, treatment-refractory)

Inclusion criteria

• {"criterion_text":"- Understand and voluntarily sign an informed consent form\n- Male or female, age ≥ 18 years at time of consent\n- Able to adhere to the study visits and protocol\n- Fulfillment of EITHER both of the following: •\t2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis (GPA) •\tAnti-PR3 antibodies titer above the laboratory threshold for positivity at screening OR both of the following: •\t2022 ACR/EULAR classification criteria for microscopic polyangiitis (MPA) •\tAnti-MPO antibodies above the laboratory threshold for positivity at screening\n- A Birmingham Vasculitis Activity Score (BVAS) of at least 3 within 12 months before screening\n- Insufficient response or intolerance to at least three months of treatment with at least two of the following therapies: rituximab, mycophenolate mofetil, azathioprin, methotrexate, cyclophosphamide, avacopan, glucocorticoids; or to at least six weeks of treatment with cyclophosphamide or plasmapheresis and rituximab combination therapy. Patients without prior rituximab treatment may also be included if treatment with rituximab is considered not advisable based on the investigator’s clinical judgment (e.g., due to contraindication, prior hypersensitivity, increased infection risk, or other medical or safety considerations\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) until 12 months after dosing of the IMP\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\n- Updated vaccination record according to the STIKO recommendations for immunocompromised patients"}

Exclusion criteria

• {"criterion_text":"- ANC < 500/µl, ALC < 100/µl or hemoglobin < 6/dl, absolute CD3+T cell count < 100/µl at screening\n- Known hypersensitivity to any drug components\n- Malignancy in the last 5 years before screening (except adequately treated basal or squamous cell skin cancer\n- Requirement for immunization with live vaccine during the study period\n- Participants who 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- Participants who are institutionalized by order of court or public authority\n- Participants participating in another clinical trial with an investigational medicinal product or medical device (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\n- Any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study, including active severe and uncontrolled infections within the last two weeks, neurologic conditions, primary immunodeficiency and history of splenectomy\n- Patients will be excluded if they are known to have any of the following: a. Any known human immunodeficiency virus (HIV) infection or positive HIV-1 or -2 antibody at Screening b. Positive 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. c. Patients 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. d. Active 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 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. Anti-metabolites: MMF/mycophenolate sodium, azathioprine, methotrexate b. Calcineurin inhibitors: eg, but not limited to cyclosporine, tacrolimus, voclosporin c. Alkylating agent: cyclophosphamide d. Janus kinase (JAK) inhibitors, Bruton tyrosine kinase (BTK) inhibitors, Tyrosine kinase 2 (TYK2) inhibitors: eg, but not limited to tofacitinib, upadacitinib, baricitinib, deucravacitinib e. Complement inhibitors: eg, but not limited to eculizumab, ravulizumab, zilucoplan, avacopan f. Plasmapheresis or intravenous immunoglobulin (IVIg) g. FcRn inhibitors: including but not limited to efartigimod, rozanolixizumab h. Any of the following (including biosimilars): Tumor necrosis factor (TNF) inhibitors: eg, but not limited to infliximab, adalimumab or anti-cytokine (IL-1, IL-6, IL-17, IL-12/23): eg, but not limited to anakinra, tocilizumab, secukinumab, ustekinumab, risankizumab i. Anti-B-cell activating factor (BAFF) or anti-a proliferation inducing ligand (APRIL): eg, but not limited to belimumab, telitacicept j. Thalidomide or thalidomide derivatives k. CD19 inhibitor: eg, but not limited to inebilizumab l. CD20 inhibitors: eg, but not limited to rituximab, ocrelizumab, obinutuzumab m. Other cell depleting therapy, anti-CD3, anti-CD4, anti-CD5\n- Prior CAR-T or TCE therapy directed at any antigen or BCMA-targeted therapy at any time\n- Life-threatening allergies, hypersensitivity, or intolerance to CND261 or its excipients or tocilizumab\n- Pregnancy or lactation\n- Females who are intending to conceive during their study participation"}

Primary endpoints

• {"endpoint_text":"- Phase I: Incidence and grading of severity of Cytokine Release Syndrome (CRS), Immune Cell Associated Neurotoxicity Syndrome (ICANS) and treatment-related adverse events (AE) and serious adverse events (SAE) due to IMP until 28 days after the last administration of CD3/CD20 TCE therapy (CND261).","definition_or_measurement_approach":"Measured as incidence and grading of severity of CRS, ICANS and treatment-related AEs/SAEs occurring up to 28 days after last administration of CND261."}
• {"endpoint_text":"- Phase II: Safety and ANCA seroconversion rate of CD3/CD20 TCE therapy (CND261) in participants with active, treatment refractory, ANCA-IgG-positive AAV","definition_or_measurement_approach":"Measured as safety events and proportion of participants achieving ANCA seroconversion following CND261 (ANCA seroconversion evaluated per antibody tests for anti-PR3 for GPA and anti-MPO for MPA)."}
• {"endpoint_text":"- Incidence and grading of severity of Cytokine Release Syndrome (CRS), Immune Cell Associated Neurotoxicity Syndrome (ICANS) and treatment-related adverse events (AE) and serious adverse events (SAE) due to IMP until 28 days after the last administration of CD3/CD20 TCE therapy (CND261).","definition_or_measurement_approach":"Measured as incidence and grading of severity of CRS, ICANS and treatment-related AEs/SAEs occurring up to 28 days after last administration of CND261."}
• {"endpoint_text":"- Percentage of patients with ANCA seroconversion after CD3/CD20 TCE (CND261) therapy (normal anti-PR3 antibodies for GPA patients and normal anti-MPO antibodies for MPA patients) at week 24","definition_or_measurement_approach":"Measured as percentage of participants with normalization of anti-PR3 (GPA) or anti-MPO (MPA) antibodies at week 24."}

Secondary endpoints

• {"endpoint_text":"- Clinical response: Duration without DMARD therapy from week 5 to week 52","definition_or_measurement_approach":"Measured as duration (weeks) without disease-modifying antirheumatic drug therapy between week 5 and week 52."}
• {"endpoint_text":"- Clinical response: Percentage of patients who reach EULAR sustained remission criteria (absence of typical signs, symptoms, or other features of active AAV) through week 52","definition_or_measurement_approach":"Measured as proportion meeting EULAR sustained remission criteria through week 52."}
• {"endpoint_text":"- Clinical response: Time until clinical relapse or flare observed between week 5 and week 52","definition_or_measurement_approach":"Measured as time-to-event (relapse/flare) between week 5 and week 52."}
• {"endpoint_text":"- Clinical response: Number of flares from week 5 through weeks","definition_or_measurement_approach":"Measured as count of disease flares occurring from week 5 through study follow-up (timepoints not fully specified)."}
• {"endpoint_text":"- Clinical response: Cumulative steroid dosage from week 5 to week 52","definition_or_measurement_approach":"Measured as cumulative corticosteroid dose administered between week 5 and week 52."}
• {"endpoint_text":"- Clinical response: Percentage of patients who reach EULAR response criteria (≥ 50% reduction of Birmingham Vasculitis Activity Score (BVAS) at week 8, 12, 24 and 52) compared to baseline","definition_or_measurement_approach":"Measured as proportion with ≥50% BVAS reduction at specified weeks compared to baseline."}
• {"endpoint_text":"- Clinical response: Change of Vasculitis Damage Index (VDI) at week 8, 12, 24 and 52 compared to baseline","definition_or_measurement_approach":"Measured as change in VDI scores at weeks 8, 12, 24 and 52 versus baseline."}
• {"endpoint_text":"- Clinical response: Change in Birmingham Vasculitis Activity Score (BVAS) at week 8, 12, 24 and 52 compared to baseline","definition_or_measurement_approach":"Measured as change in BVAS at specified timepoints compared to baseline."}
• {"endpoint_text":"- Clinical response: Change in patient’s Global Assessment (PtGA) of disease activity (VAS 0-100mm) over time","definition_or_measurement_approach":"Measured as change in PtGA VAS (0-100mm) over study visits."}
• {"endpoint_text":"- Change in physician’s Global Assessment (PhGA) of disease activity (VAS 0-100mm) over time","definition_or_measurement_approach":"Measured as change in PhGA VAS (0-100mm) over study visits."}
• {"endpoint_text":"- Clinical response: Change in Short Form 36 (SF-36, quality of life questionnaire) over time","definition_or_measurement_approach":"Measured as change in SF-36 scores over time."}
• {"endpoint_text":"- Clinical response: Change in Health Assessment Questionnaire Disability Index (HAQ-DI) over time","definition_or_measurement_approach":"Measured as change in HAQ-DI over time."}
• {"endpoint_text":"- Cellular and humoral response: Percentage of patients with ANCA seroconversion after CD3/CD20 TCE (CND261) therapy (normal anti-PR3 antibodies for GPA patients and normal anti-MPO antibodies for MPA patients) at week 8, 24 (Phase I), 12, and 52","definition_or_measurement_approach":"Measured as percentage with normalization of anti-PR3/anti-MPO antibodies at specified weeks."}
• {"endpoint_text":"- Cellular and humoral response: Change in levels of anti-PR3 antibodies (GPA) and anti-MPO antibodies (MPA) over time","definition_or_measurement_approach":"Measured as quantitative changes in anti-PR3 and anti-MPO antibody levels over time."}
• {"endpoint_text":"- Cellular and humoral response: Change in the number of CD20+ B cell numbers over time","definition_or_measurement_approach":"Measured as change in CD20+ B cell counts over time."}
• {"endpoint_text":"- Cellular and humoral response: Change in levels of total IgG, IgA, IgM immunoglobulins over time","definition_or_measurement_approach":"Measured as changes in total IgG, IgA, and IgM levels over time."}
• {"endpoint_text":"- Cellular and humoral response: Change in eGFR and levels of CRP over time","definition_or_measurement_approach":"Measured as changes in eGFR and CRP levels over time."}
• {"endpoint_text":"- Safety: Any AE and SAE until end of study","definition_or_measurement_approach":"Captured as incidence of any adverse events and serious adverse events until study end."}
• {"endpoint_text":"- Safety: Type and severity, seriousness and relatedness of AEs","definition_or_measurement_approach":"Characterised by type, severity, seriousness and relationship to IMP for reported AEs."}

Germany

Earliest CTIS Part Ii Submission Date

19-01-2026

Latest Decision Or Authorization Date

30-01-2026

Processing Time Days

11

Number Of Sites

1

Number Of Participants

8

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":"Monetary support","organisation_type":""}