A Study to Assess the Effect of Surovatamig in Adult Participants With Antibody-mediated Kidney Disease

Official title

A Phase 2, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Surovatamig in Adults With Antibody-mediated Kidney Disease

Overview

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

• Drug Surovatamig
  Participants will receive Surovatamig subcutaneously

Primary outcome measures

• Number of participants with adverse events. [Time frame: Through study completion, an average of 2 years]
• Change from baseline in UPCR (from 24-hour urine collection or the intended 24-hour urine collection) [Time frame: At 6 months]

Secondary outcome measures (12)

• Percentage of participants achieving complete or partial remission of pMN [Time frame: At 24 months]
• Percentage of participants achieving complete remission of pMN [Time frame: At 24 months]
• Percentage of participants achieving partial remission of pMN [Time frame: At 24 months]
• Change from baseline in UPCR (from 24-hour urine collection or the intended 24-hour urine collection) [Time frame: At 24 months]
• Change from baseline in anti-PLA2R antibody titer [Time frame: At 24 months]
• Change from baseline in B-cell count in peripheral blood [Time frame: At 24 months]
• Time to relapse after complete or partial remission [Time frame: At 24 months]
• Time to a ≥ 3 months sustained reduction of eGFR [Time frame: From Baseline to 24 months]
• Change from baseline in patient-reported experience of symptoms associated with pMN [Time frame: Through study completion, an average of 2 years]
• Serum PK parameters of surovatamig, AUC Area under the plasma concentration versus time curve [Time frame: Through study completion, an average of 2 years]
• Treatment-emergent ADAs [Time frame: Through study completion, an average of 2 years]
• Serum PK parameters of surovatamig, as Cmax (Peak Plasma Concentration) [Time frame: Through study completion, an average of 2 years]

Eligibility criteria

Inclusion criteria

• 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.
• Diagnosis of anti-PLA2R antibody-positive pMN.
• 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.
• Positive for anti-PLA2R.
• Up to date with required vaccinations as per institutional guidelines (eg, influenza, pneumococcal, and severe acute respiratory syndrome coronavirus 2) prior to study entry.
• 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.
• Capable of giving signed informed consent

Exclusion criteria

• Receipt of B cell-depleting therapy including CD19- or CD20-directed monoclonal antibodies < 9 months before screening.
• Immunomodulatory therapy <3 months before screening.
• Secondary causes of membranous nephropathy
• Diabetes mellitus with haemoglobin A1C > 8.5% tested at screening visit.
• Malignancies
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• Research Site — Los Angeles
• Research Site — Iowa City
• Research Site — Bethesda
• Research Site — New York
• Research Site — Houston
• Research Site — Houston

France · 5 centers

• Research Site — Bordeaux
• Research Site — Créteil
• Research Site — Lyon
• Research Site — Nantes
• Research Site — Nîmes

Italy · 4 centers

• Research Site — Brescia
• Research Site — Rozzano
• Research Site — Torino
• Research Site — Verona

Spain · 2 centers

• Research Site — Barcelona
• Research Site — Madrid

United Kingdom · 2 centers

• Research Site — London
• Research Site — Manchester

Belgium · 1 center

• Research Site — Ieper

Germany · 1 center

• Research Site — Düsseldorf

Poland · 1 center

• Research Site — Lodz

Identifiers

NCT: NCT07571746 · D740FC00001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗