Sökning: WFRF:(Millns Helen) >
Pharmacodynamic eva...
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
-
- Wechalekar, Ashutosh (författare)
- UCL, Gower St, London WC1E 6BT, England.
-
- Antoni, Gunnar (författare)
- Uppsala universitet,Plattformen för Preklinisk PET-MRI,Preparativ läkemedelskemi,Science for Life Laboratory, SciLifeLab
-
- Al Azzam, Wasfi (författare)
- GlaxoSmithKline, Philadelphia, PA USA.;Takeda, Lexington, MA USA.
-
visa fler...
-
- Bergstrom, Mats (författare)
- GlaxoSmithKline, Stevenage, Herts, England.
-
- Biswas, Swethajit (författare)
- GlaxoSmithKline, Stevenage, Herts, England.;Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England.
-
- Chen, Chao (författare)
- GlaxoSmithKline, Stevenage, Herts, England.
-
- Cheriyan, Joseph (författare)
- Cambridge Univ Hosp NHS Fdn Trust, Cambridge, England.
-
- Cleveland, Matthew (författare)
- GlaxoSmithKline, Stevenage, Herts, England.
-
- Cookson, Louise (författare)
- GlaxoSmithKline, Cambridge, England.
-
- Galette, Paul (författare)
- GlaxoSmithKline, Philadelphia, PA USA.
-
- Janiczek, Robert L. (författare)
- GlaxoSmithKline, Stevenage, Herts, England.
-
- Kwong, Raymond Y. (författare)
- Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
-
- Lukas, Mary Ann (författare)
- GlaxoSmithKline, Philadelphia, PA USA.
-
- Millns, Helen (författare)
- GlaxoSmithKline, Stevenage, Herts, England.
-
- Richards, Duncan (författare)
- GlaxoSmithKline, Stevenage, Herts, England.;Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England.
-
- Schneider, Ian (författare)
- GlaxoSmithKline, Cambridge, England.;Consolidated Consulting LTD, Cambridge, England.
-
- Solomon, Scott D. (författare)
- Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
-
- Sörensen, Jens (författare)
- Uppsala universitet,Klinisk fysiologi,Radiologi
-
- Storey, James (författare)
- GlaxoSmithKline, Stevenage, Herts, England.
-
- Thompson, Douglas (författare)
- GlaxoSmithKline, Stevenage, Herts, England.
-
- van Dongen, Guus (författare)
- Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam, Netherlands.
-
- Vugts, Danielle J. (författare)
- Vrije Univ Amsterdam, Amsterdam UMC, Amsterdam, Netherlands.
-
- Wall, Anders (författare)
- Uppsala universitet,Radiologi
-
- Wikström, Gerhard (författare)
- Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR),Klinisk epidemiologi,Uppsala Univ, Inst Med Vetenskaper, Uppsala, Sweden.
-
- Falk, Rodney H. (författare)
- Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
-
visa färre...
-
UCL, Gower St, London WC1E 6BT, England Plattformen för Preklinisk PET-MRI (creator_code:org_t)
- 2022-02-13
- 2022
- Engelska.
-
Ingår i: BMC Cardiovascular Disorders. - : BioMed Central (BMC). - 1471-2261 .- 1471-2261. ; 22:1
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
https://bmccardiovas...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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 [Zr-89]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 [Zr-89]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 [Zr-89]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 patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018).
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
Nyckelord
- Cardiac amyloidosis
- Miridesap
- Dezamizumab
- Positron emission tomography
- Immuno-PET
- Serum amyloid P component
- Systemic amyloidosis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Wechalekar, Ashu ...
-
Antoni, Gunnar
-
Al Azzam, Wasfi
-
Bergstrom, Mats
-
Biswas, Swethaji ...
-
Chen, Chao
-
visa fler...
-
Cheriyan, Joseph
-
Cleveland, Matth ...
-
Cookson, Louise
-
Galette, Paul
-
Janiczek, Robert ...
-
Kwong, Raymond Y ...
-
Lukas, Mary Ann
-
Millns, Helen
-
Richards, Duncan
-
Schneider, Ian
-
Solomon, Scott D ...
-
Sörensen, Jens
-
Storey, James
-
Thompson, Dougla ...
-
van Dongen, Guus
-
Vugts, Danielle ...
-
Wall, Anders
-
Wikström, Gerhar ...
-
Falk, Rodney H.
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Kardiologi
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Radiologi och bi ...
- Artiklar i publikationen
-
BMC Cardiovascul ...
- Av lärosätet
-
Uppsala universitet