Safety and Efficacy of Tarperprumig in Adult Participants with ANCA-Associated Vasculitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alexion Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

25 Nov 2025 → ongoing

Decision date (initial)

2025-11-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Alexion Pharmaceutical, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

To evaluate the safety and tolerability of tarperprumig in participants with newly diagnosed or relapsing ANCA‑associated vasculitis.

Secondary objectives 2

1. To evaluate the efficacy of treatment with tarperprumig on achieving disease remission, sustained remission, and preventing relapse in participants newly diagnosed or relapsing ANCA
2. To evaluate the efficacy of treatment with tarperprumig on kidney function and kidney damage in participants with newly diagnosed or relapsing ANCA-associated vasculitis

Conditions and MedDRA coding

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age: Participants aged 18 to 80 years (inclusive) at the time of consent.
2. Type of Participant and Disease Characteristics: Newly diagnosed or relapsing ANCA-associated vasculitis, GPA and MPA subtypes consistent with the 2022 ACR/EULAR classification criteria for GPA and MPA for whom treatment with rituximab or cyclophosphamide is considered.
3. Positive test for antibodies to either PR3-ANCA or MPO-ANCA at Screening or in the past by a quantitative assay (for example, ELISA, bead assay, etc).
4. At least one major item, or at least 3 minor items, or at least 2 renal items in the BVAS.
5. Estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2 (calculated using the 2021 CKD EPI equation without race coefficient) at Screening (Section 8.2.6).
6. Weight: There is no weight restriction in this study.
7. All participants must agree to follow protocol-specified contraception guidance as outlined in the study protocol. Contraceptive use must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male participants: Participants are eligible to participate if they agree to the following during the study intervention treatment period and for at least [CCI] after the last dose of study intervention: • Refrain from donating sperm • Be abstinent from intercourse where pregnancy can occur (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below  Agree to use an external condom and should also be advised of the benefit for a partner of CBP to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a partner able to give birth who is not currently pregnant  Agree to use an external condom when engaging in any activity that allows for passage of ejaculate to another person. b. Female participants: A participant is eligible to participate if not pregnant or breastfeeding, and one of the following conditions applies: • Is a woman of NCBP as defined in Section 10.5 Contraceptive and Barrier Guidance. • Is of CBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), preferably with low user dependency, as described in Section 10.5 Contraceptive and Barrier Guidance during the study intervention treatment period and for at least [CCI] after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The Investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention. • A CBP participant must have a negative highly sensitive pregnancy test (urine) as required by local regulations) within 24 hours before the first dose of study intervention, see Section 8.3.6 Pregnancy Testing.  If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. • Additional requirements for pregnancy testing during and after study intervention are located in Section 8.3.6 Pregnancy Testing. • The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a participant with an early undetected pregnancy.
8. Informed Consent: Willing and able to give written informed consent and to comply with the requirements of the study protocol.

Exclusion criteria 19

1. Medical Conditions: Other systemic diseases that, in the judgment of the Investigator, constitute the primary illness, including but not limited to: eosinophilic granulomatosis with polyangiitis (EGPA), systemic lupus erythematosus, IgA nephropathy and/or IgA-associated vasculitis with or without Henoch-Schönlein purpura, rheumatoid vasculitis, Sjögren's syndrome, anti-GBM disease, cryoglobulinemic vasculitis, autoimmune hemolytic anemia, or mixed connective tissue disease.
2. Alveolar hemorrhage requiring invasive pulmonary ventilation support at Screening.
3. Any diseases or conditions that, in the judgment of the Investigator, present a substantial clinical risk to participate in this study.
4. For patients with a previous diagnosis of CKD, patients known to have a stable eGFR for greater than 3 months prior to Screening and a decline less than 25% of previous eGFR at Screening will be excluded.
5. Known hypersensitivity to any ingredient contained in the study intervention.
6. History of serious N meningitidis infection.
7. Current and/or history (within the previous 5 years) of drug and/or alcohol abuse and/or dependence.
8. Evidence of active hepatitis B, hepatitis C, and/or HIV infection. Only participants with documented negative historical results (within [CCI] before Screening) for HBV, HCV, and HIV or a negative test by screening can be included into the study. Evidence of hepatitis B or hepatitis C infections will be according to the following criteria at Screening: • Testing positive for HBsAg, OR • Testing positive for HBcAb while having a negative HBsAb. • Positive hepatitis C antibody test result at Screening or within 3 months unless HCV RNA negative test is documented. Note: HBV DNA testing may be performed instead of HBsAb as per local standard practice.
9. Evidence of hepatic disease: AST, ALT, ALP, or bilirubin > 3 times the ULN at Screening.
10. Evidence of latent or active TB (Section 8.1.9).
11. History of complement deficiency.
12. History of splenectomy.
13. History of malignancy, lymphoproliferative, or myeloproliferative disorder within 5 years prior to Screening with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
14. Prior/Concomitant Therapy Has received any of the following: a. A kidney transplant b. Dialysis or plasma exchange within [CCI] before Screening c. Cyclophosphamide within [CCI] before Screening d. [CCI] or other B cell or plasma cell-depleting agent within 12 months to > 14 days before Screening e. A cumulative dose of intravenous [CCI] greater than 3 g methylprednisolone equivalent within 4 weeks of Screening f. Oral daily dose of a glucocorticoid of > 10 mg prednisone equivalent for more than [CCI] continuously prior to the Screening Visit g. [CCI] or other complement inhibitors (eculizumab, ravulizumab, etc) within 30 days or 5 half-lives, whichever is longer, before Screening h. Anti-tumor necrosis factor treatment, abatacept, alemtuzumab, IVIG, antithymocyte globulin, or any other experimental or biological therapy within 12 weeks or 5 half-lives, whichever is longer, before Screening.
15. Prior/Concurrent Clinical Study Experience Participation in a clinical study involving an investigational medical product or device within 30 days or 5 half-lives of the investigational drug, whichever is longer, before screening
16. Diagnostic Assessments: The following abnormal laboratory findings at Screening: • IgG < 5 g/L (if [CCI] treatment is initiated before Screening, then test results before initiation of [CCI] and within 6 months of the Screening can be used) • WBC count (3500/µL), or neutrophil count less than 1500/μL
17. Women who are pregnant (positive pregnancy test) or breastfeeding at study entry
18. Participants with an active systemic bacterial, viral, fungal, or parasitic infection, with the diagnostic assessment at the discretion of the investigator, that required use of intravenous antibacterials, antivirals, antifungals, or anti-parasitic agents within 14 days prior to Day 1.
19. Participants with any contraindication to rituximab per the locally approved product information, or any label warning/precaution that in the Investigator’s judgment would prevent safe rituximab administration in this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of TEAEs and TESAEs.
2. Changes from Baseline in safety assessments (vital sign measurements, physical examination, clinical laboratory tests, and ECG results).

Secondary endpoints 12

1. Achieving disease remission at Week 26.
2. Achieving sustained remission at Week 52.
3. Achieving BVAS = 0 at [CCI], 26, and 52.
4. Relapse after previously achieving disease remission at Week 26.
5. Time to first relapse after having achieved disease remission at Week 26.
6. Change from Baseline in Vasculitis Damage Index (VDI) at [CCI] 26, and 52.
7. Time to first occurrence of BVAS = 0.
8. Change from Baseline in BVAS at all timepoints.
9. Change from Baseline in eGFR (mL/min per 1.73 m2) at [CCI] 26, and 52.
10. Change from Baseline in proteinuria based on spot UPCR (mg/g) and % change from Baseline at [CCI] 26, and 52.
11. Change from Baseline in proteinuria based on spot UACR (mg/g) and % change from Baseline at [CCI] 26, and 52.
12. Hematuria change from Baseline (RBCs/HPF) and % change from Baseline at [CCI] 26, and 52.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alexion Pharmaceuticals Inc.

Sponsor organisation

Alexion Pharmaceuticals Inc.

Address

121 Seaport Boulevard

City

Boston

Postcode

02210-2050

Country

United States

Scientific contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Public contact point

Organisation

Alexion Pharmaceuticals Inc.

Contact name

European Clinical Trial Information

Locations

5 EU/EEA countries · 23 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 51 files

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

Application history

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