An open label, phase I/II study investigating the safety and efficacy of a CD3/CD20 bispecific T-cell engager therapy in patients with active, treatment refractory, ANCA-IgG-positive associated vasculitis. The RENEWAL study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

27 Feb 2026 → ongoing

Decision date (initial)

2026-01-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Candid Therapeutics

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Primary objective Phase I: Safety; To assess the safety of CD3/CD20 TCE cell therapy in participants with active, treatment refractory,
ANCA-IgG-positive AAV
Primary objective Phase II: Safety and efficacy; To assess the safety and ANCA seroconversion rate of CD3/CD20 TCE therapy (CND261) in participants
with active, treatment refractory, ANCA-IgG-positive AAV

Secondary objectives 3

1. Clinical response: To assess the Clinical efficacy response after CD3/CD20 TCE therapy (CND261)
2. Cellular and humoral response: To assess the cellular and humoral response after CD3/CD20 TCE therapy (CND261)
3. Safety: To assess AEs and SAEs including those not encompassed by the primary endpoint

Conditions and MedDRA coding

Active, treatment refractory, ANCA-IgG-positive associated vasculitis

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Understand and voluntarily sign an informed consent form
2. Male or female, age ≥ 18 years at time of consent
3. Able to adhere to the study visits and protocol
4. Fulfillment of EITHER both of the following: • 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis (GPA) • Anti-PR3 antibodies titer above the laboratory threshold for positivity at screening OR both of the following: • 2022 ACR/EULAR classification criteria for microscopic polyangiitis (MPA) • Anti-MPO antibodies above the laboratory threshold for positivity at screening
5. A Birmingham Vasculitis Activity Score (BVAS) of at least 3 within 12 months before screening
6. 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
7. 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
8. 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
9. Updated vaccination record according to the STIKO recommendations for immunocompromised patients

Exclusion criteria 17

1. ANC < 500/µl, ALC < 100/µl or hemoglobin < 6/dl, absolute CD3+T cell count < 100/µl at screening
2. Severely impaired liver (Child Pugh C), cardiac or pulmonory (NYHA IV) function
3. 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
4. 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.
5. 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
6. Prior CAR-T or TCE therapy directed at any antigen or BCMA-targeted therapy at any time
7. Life-threatening allergies, hypersensitivity, or intolerance to CND261 or its excipients or tocilizumab
8. Pregnancy or lactation
9. Females who are intending to conceive during their study participation
10. Known hypersensitivity to any drug components
11. Malignancy in the last 5 years before screening (except adequately treated basal or squamous cell skin cancer
12. Requirement for immunization with live vaccine during the study period
13. Participants who are incapable to understand the aim, importance and consequences of the study and to give legal informed consent
14. 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
15. Participants who possibly are dependent on the Sponsor, the Principal Investigator or Investigator (e.g. family members)
16. Participants who are institutionalized by order of court or public authority
17. 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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. 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).
2. Phase II: Safety and ANCA seroconversion rate of CD3/CD20 TCE therapy (CND261) in participants with active, treatment refractory, ANCA-IgG-positive AAV
3. 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).
4. 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

Secondary endpoints 19

1. Clinical response: Duration without DMARD therapy from week 5 to week 52
2. 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
3. Clinical response: Time until clinical relapse or flare observed between week 5 and week 52
4. Clinical response: Number of flares from week 5 through weeks
5. Clinical response: Cumulative steroid dosage from week 5 to week 52
6. 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
7. Clinical response: Change of Vasculitis Damage Index (VDI) at week 8, 12, 24 and 52 compared to baseline
8. Clinical response: Change in Birmingham Vasculitis Activity Score (BVAS) at week 8, 12, 24 and 52 compared to baseline
9. Clinical response: Change in patient’s Global Assessment (PtGA) of disease activity (VAS 0-100mm) over time
10. Change in physician’s Global Assessment (PhGA) of disease activity (VAS 0-100mm) over time
11. Clinical response: Change in Short Form 36 (SF-36, quality of life questionnaire) over time
12. Clinical response: Change in Health Assessment Questionnaire Disability Index (HAQ-DI) over time
13. 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
14. Cellular and humoral response: Change in levels of anti-PR3 antibodies (GPA) and anti-MPO antibodies (MPA) over time
15. Cellular and humoral response: Change in the number of CD20+ B cell numbers over time
16. Cellular and humoral response: Change in levels of total IgG, IgA, IgM immunoglobulins over time
17. Cellular and humoral response: Change in eGFR and levels of CRP over time
18. Safety: Any AE and SAE until end of study
19. Safety: Type and severity, seriousness and relatedness of AEs

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Sponsor organisation

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Address

Theodor-Stern-Kai 7, Sachsenhausen Sachsenhausen

City

Frankfurt Am Main

Postcode

60596

Country

Germany

Scientific contact point

Organisation

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Contact name

Prof. Dr. med. Dr. rer. bio. hum. David Simon

Public contact point

Organisation

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

Contact name

Dr. Isabel Dittmann

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 7 files

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

Application history

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