Phase 2, Randomized, Double-Blind, Placebo-controlled, Parallel-Group, Multicenter Study to Evaluate the Safety and Efficacy of Tarperprumig in Adult Participants with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Trial ID: 2025-521706-17-00
Protocol: ALXN1820-ANCA-201
Sponsor: Alexion Pharmaceuticals Inc.

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

Diseases & Conditions

Anti-neutrophil cytoplasmic antibody positive vasculitis

Objectives

The primary objective is to evaluate the **safety** and **tolerability** of **tarperprumig** in participants with newly diagnosed or relapsing **ANCA-associated vasculitis**. This assessment is clinically relevant as it establishes the baseline safety profile of this **bispecific monoclonal antibody** targeting **complement factor properdin** in a patient population characterized by systemic **autoimmune** inflammation and potential multi-organ involvement.

The secondary objectives include:

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

• To evaluate the efficacy of treatment with tarperprumig on **kidney function** and **kidney damage** in participants with newly diagnosed or relapsing ANCA-associated vasculitis.

Participants

The clinical trial enrolled a total of **54 participants** diagnosed with **anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis**, including both **granulomatosis with polyangiitis (GPA)** and **microscopic polyangiitis (MPA)** subtypes. The study population consisted of both **male and female participants** aged **18 to 80 years** at the time of consent. Participants were selected based on having newly diagnosed or relapsing disease consistent with the 2022 ACR/EULAR classification criteria, for whom treatment with **rituximab** or **cyclophosphamide** was considered appropriate. All participants had a positive test for antibodies to either **PR3-ANCA** or **MPO-ANCA** at screening or documented in their medical history by a quantitative assay. Disease activity was confirmed by the presence of at least one major item, or at least three minor items, or at least two renal items in the **Birmingham Vasculitis Activity Score (BVAS)**. Participants were required to have an **estimated glomerular filtration rate (eGFR)** of at least 15 mL/min/1.73 m² calculated using the 2021 CKD EPI equation without race coefficient. No weight restrictions were applied in this study. Female participants of childbearing potential were required to use highly effective contraceptive methods with a failure rate of less than 1% per year during the study intervention period and for a specified period after the last dose, and to have a negative pregnancy test within 24 hours before the first dose. Male participants were required to use barrier contraception and refrain from donating sperm during the treatment period and for a specified period thereafter.

Plans and Procedures

This is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial designed to evaluate the safety and efficacy of **tarperprumig** in adult participants with **anti-neutrophil cytoplasmic antibody-associated vasculitis**. The study investigates tarperprumig, a humanised bispecific monoclonal antibody against complement factor properdin and albumin, administered as a **solution for injection** via **subcutaneous injection**. The comparator is tarperprumig placebo. The primary objective is to evaluate the safety and tolerability of tarperprumig in participants with newly diagnosed or relapsing ANCA-associated vasculitis. The maximum treatment period is 52 weeks.

The trial will enroll participants aged 18 to 80 years with newly diagnosed or relapsing ANCA-associated vasculitis, including **granulomatosis with polyangiitis** and **microscopic polyangiitis** subtypes consistent with the 2022 ACR/EULAR classification criteria, for whom treatment with **rituximab** or **cyclophosphamide** is considered. Eligible participants must have a positive test for antibodies to either **PR3-ANCA** or **MPO-ANCA** at screening or in the past by a quantitative assay. Disease activity must be documented by at least one major item, or at least 3 minor items, or at least 2 renal items in the **Birmingham Vasculitis Activity Score**. Participants must have an **estimated glomerular filtration rate** of at least 15 mL/min/1.73 m² calculated using the 2021 CKD EPI equation without race coefficient at screening. There is no weight restriction in this study. Female participants of childbearing potential must use highly effective contraception with a failure rate of less than 1% per year during the study intervention treatment period and for a specified period after the last dose of study intervention, and must have a negative highly sensitive pregnancy test within 24 hours before the first dose. Male participants must agree to use contraception and refrain from donating sperm during the treatment period and for a specified period after the last dose.

The primary endpoints include the incidence of **treatment-emergent adverse events** and **treatment-emergent serious adverse events**, as well as changes from baseline in safety assessments including vital sign measurements, physical examination, clinical laboratory tests, and **electrocardiogram** results. Secondary endpoints include achieving disease remission at Week 26, achieving sustained remission at Week 52, achieving BVAS equal to 0 at specified timepoints including Weeks 26 and 52, relapse after previously achieving disease remission at Week 26, time to first relapse after having achieved disease remission at Week 26, change from baseline in **Vasculitis Damage Index** at specified timepoints including Weeks 26 and 52, time to first occurrence of BVAS equal to 0, change from baseline in BVAS at all timepoints, change from baseline in eGFR at specified timepoints including Weeks 26 and 52, change from baseline in proteinuria based on spot **urine protein-to-creatinine ratio** and percentage change from baseline at specified timepoints including Weeks 26 and 52, change from baseline in proteinuria based on spot **urine albumin-to-creatinine ratio** and percentage change from baseline at specified timepoints including Weeks 26 and 52, and hematuria change from baseline measured in red blood cells per high-power field and percentage change from baseline at specified timepoints including Weeks 26 and 52.

The estimated recruitment start date is November 2025, and the estimated end date is February 2028. Participant involvement in the study is expected to last up to 52 weeks during the treatment period. Conditions that may lead to early termination from the study are not specified in the available data.

Treatment

**Tarperprumig** is the experimental medicinal product being evaluated in this clinical trial. The active substance is tarperprumig, also known by the sponsor product code **ALXN1820**, which is a humanised bispecific monoclonal antibody against complement factor properdin and albumin. The substance is classified as a protein of other origin. Tarperprumig is formulated as a **solution for injection** and is administered via **subcutaneous injection**. The maximum treatment period is 52 weeks. The product is manufactured by Alexion Pharmaceuticals, Inc.

**Tarperprumig Placebo** serves as the comparator treatment in this randomized, double-blind, placebo-controlled study. The placebo is used to maintain blinding and enable comparison of safety and efficacy outcomes between the experimental treatment group and the control group. Specific details regarding the pharmaceutical form, route of administration, and dosage of the placebo are not specified in the available documentation.

Efficacy

Efficacy will be assessed through multiple parameters measured at specified timepoints throughout the study. The primary efficacy endpoints include the incidence of treatment-emergent adverse events and treatment-emergent serious adverse events, as well as changes from baseline in safety assessments encompassing vital sign measurements, physical examination findings, clinical laboratory tests, and electrocardiogram results.

Secondary efficacy endpoints will evaluate disease activity and remission status. These include achieving disease remission at Week 26, achieving sustained remission at Week 52, and achieving a Birmingham Vasculitis Activity Score equal to zero at Week 26 and Week 52. Additional parameters include the assessment of relapse after previously achieving disease remission at Week 26, time to first relapse after having achieved disease remission at Week 26, and time to first occurrence of Birmingham Vasculitis Activity Score equal to zero. Changes from baseline in the Vasculitis Damage Index will be measured at Week 26 and Week 52. Changes from baseline in Birmingham Vasculitis Activity Score will be assessed at all timepoints throughout the study.

Renal function parameters will be evaluated through changes from baseline in estimated glomerular filtration rate measured in milliliters per minute per 1.73 square meters at Week 26 and Week 52. Proteinuria will be assessed based on spot urine protein-to-creatinine ratio measured in milligrams per gram, with both absolute and percentage changes from baseline recorded at Week 26 and Week 52. Similarly, proteinuria based on spot urine albumin-to-creatinine ratio measured in milligrams per gram will be evaluated with absolute and percentage changes from baseline at Week 26 and Week 52. Hematuria will be assessed through changes from baseline in red blood cells per high-power field, with both absolute and percentage changes measured at Week 26 and Week 52.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Age: Participants aged 18 to 80 years (inclusive) at the time of consent.
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.
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).
At least one major item, or at least 3 minor items, or at least 2 renal items in the BVAS.
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).
Weight: There is no weight restriction in this study.
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.
Informed Consent: Willing and able to give written informed consent and to comply with the requirements of the study protocol.

cancel

Exclusion Criteria

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.
Alveolar hemorrhage requiring invasive pulmonary ventilation support at Screening.
Any diseases or conditions that, in the judgment of the Investigator, present a substantial clinical risk to participate in this study.
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.
Known hypersensitivity to any ingredient contained in the study intervention.
History of serious N meningitidis infection.
Current and/or history (within the previous 5 years) of drug and/or alcohol abuse and/or dependence.
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.
Evidence of hepatic disease: AST, ALT, ALP, or bilirubin > 3 times the ULN at Screening.
Evidence of latent or active TB (Section 8.1.9).
History of complement deficiency.
History of splenectomy.
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.
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.
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
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
Women who are pregnant (positive pregnancy test) or breastfeeding at study entry
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.
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.