Primary Membranous Nephropathy
Conditions
Brief summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetic, and efficacy of surovatamig administered by subcutaneous injection in adult participants with primary membranous nephropathy.
Detailed description
This is a Phase II open-label study to assess the safety, tolerability, Pharmacokinetics, and efficacy of surovatamig in adult participants with pMN, who are positive for anti-PLA2R antibodies and have heavy and persistent proteinuria with a high risk of progressing to end stage kidney disease. The study will be conducted across approximately 30 to 40 study sites in approximately 10 countries. The study consists of 2 parts (Part A Multiple ascending with sentinel dosing and Part B Multiple ascending doses), with each consisting of 3 periods (ie, screening period, treatment period, and follow-up period; up to 26 months in total).
Interventions
DRUGSurovatamig
Participants will receive Surovatamig subcutaneously
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study consists of 2 parts (Part A and Part B), with each consisting of 3 periods (ie, screening period, treatment period, and follow-up period; up to 26 months in total).
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 75 years of age inclusive, at the time of signing the informed consent. 2. Diagnosis of anti-PLA2R antibody-positive pMN. 3. All participants must have received SoC therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for ≥ 4 weeks, with exceptions in case of intolerance, contraindications, or low blood pressure, before the screening period. 4. Positive for anti-PLA2R. 5. Up to date with required vaccinations as per institutional guidelines (eg, influenza, pneumococcal, and severe acute respiratory syndrome coronavirus 2) prior to study entry. 6. Male and/or female assigned at birth, inclusive of all gender identities. Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 7. Capable of giving signed informed consent
Exclusion criteria
1. Receipt of B cell-depleting therapy including CD19- or CD20-directed monoclonal antibodies \< 9 months before screening. 2. Immunomodulatory therapy \<3 months before screening. 3. Secondary causes of membranous nephropathy 4. Diabetes mellitus with haemoglobin A1C \> 8.5% tested at screening visit. 5. Malignancies 6. History of HLH/MAS. 7 Significant CNS co-morbidity 8\. History of chronic significant respiratory disease. 9. Significant opportunistic infection in the medical history deemed relevant by the Investigator. 10\. Abnormal vital sign after 10 minutes sitting at rest. 11. Administration of corticosteroids such as prednisolone at doses exceeding 20 mg or an equivalent agent \< 2 months before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events. | Through study completion, an average of 2 years | To assess the safety and tolerability of surovatamig on adverse events, including Adverse events, Serious adverse events, Adverse event of special interests, and Adverse events leading to discontinuation of surovatamig. |
| Change from baseline in UPCR (from 24-hour urine collection or the intended 24-hour urine collection) | At 6 months | To assess the effect of surovatamig on proteinuria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants achieving complete or partial remission of pMN | At 24 months | To evaluate the proportion of participants who achieve partial and/or complete remission |
| Percentage of participants achieving complete remission of pMN | At 24 months | To evaluate the proportion of participants who achieved complete remission |
| Percentage of participants achieving partial remission of pMN | At 24 months | To evaluate the proportion of participants who achieve partial remission |
| Change from baseline in UPCR (from 24-hour urine collection or the intended 24-hour urine collection) | At 24 months | To assess the effect of surovatamig on proteinuria |
| Change from baseline in anti-PLA2R antibody titer | At 24 months | To evaluate anti-PLA2R antibodies in blood |
| Change from baseline in B-cell count in peripheral blood | At 24 months | To assess the effect of surovatamig by assessment of B-cell depletion in blood |
| Time to relapse after complete or partial remission | At 24 months | Time to relapse after complete or partial remission |
| Time to a ≥ 3 months sustained reduction of eGFR | From Baseline to 24 months | Time to a sustained reduction of eGFR |
| Change from baseline in patient-reported experience of symptoms associated with pMN | Through study completion, an average of 2 years | To evaluate the change in patient-reported experience |
| Serum PK parameters of surovatamig, AUC Area under the plasma concentration versus time curve | Through study completion, an average of 2 years | To characterise the PK of surovatamig |
| Treatment-emergent ADAs | Through study completion, an average of 2 years | To evaluate the immunogenicity of surovatamig |
| Serum PK parameters of surovatamig, as Cmax (Peak Plasma Concentration) | Through study completion, an average of 2 years | To characterise the PK of surovatamig |
Countries
Belgium, France, Germany, Italy, Poland, Spain, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed