| Title: |
Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study |
| Authors: |
Wechalekar, A; Antoni, G; Al Azzam, W; Bergström, M; Biswas, S; Chen, C; Cheriyan, J; Cleveland, M; Cookson, L; Galette, P; Janiczek, RL; Kwong, RY; Lukas, MA; Millns, H; Richards, D; Schneider, I; Solomon, SD; Sörensen, J; Storey, J; Thompson, D; van Dongen, G; Vugts, DJ; Wall, A; Wikström, G; Falk, RH |
| Publisher Information: |
BioMed Central |
| Publication Year: |
2022 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
Background In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis. Methods Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients received ≤ 6 monthly doses of dezamizumab in the Phase 2 trial (n = 7), ≤ 2 doses of non-radiolabelled dezamizumab plus [89Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (n = 2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [89Zr]Zr-dezamizumab cardiac uptake assessed via PET. Results Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [89Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks. Conclusions Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1186/s12872-021-02407-6 |
| Availability: |
https://doi.org/10.1186/s12872-021-02407-6; https://ora.ox.ac.uk/objects/uuid:1a9ed7b9-969c-4f96-bd07-4c297b95ba30 |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.93DB64B1 |
| Database: |
BASE |