Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double-blind, placebo-controlled, dose-titration trial.

Muscle & Nerve
Kathryn R WagnerPerry B Shieh

Abstract

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene resulting in the absence of dystrophin. Casimersen is a phosphorodiamidate morpholino oligomer designed to bypass frameshift DMD mutations and produce internally truncated, yet functional, dystrophin protein in patients amenable to exon 45 skipping. Our primary study objective was to evaluate safety and tolerability of casimersen; the secondary objective was to characterize the plasma pharmacokinetics. This multicenter, phase 1/2 trial enrolled 12 participants (aged 7-21 years, who had limited ambulation or were nonambulatory) and comprised a 12-week, double-blind dose titration, then an open-label extension for up to 132 weeks. During dose titration, participants were randomized 2:1 to weekly casimersen infusions at escalating doses of 4, 10, 20, and 30 mg/kg (≥2 weeks per dose), or placebo. Participants received casimersen for a mean 139.6 weeks. Treatment-emergent adverse events (TEAEs) occurred in all casimersen- and placebo-treated participants and were mostly mild (over 91.4%) and unrelated to casimersen or its dose. There were no deaths, dose reductions, abnormalities in laboratory parameters or vital signs, or casimersen-related serious AEs. Casime...Continue Reading

References

Jan 22, 2009·Human Mutation·Annemieke Aartsma-RusJohan T den Dunnen
Aug 3, 2013·Annals of Neurology·Jerry R MendellUNKNOWN Eteplirsen Study Group
Nov 18, 2015·Annals of Neurology·Jerry R MendellUNKNOWN Eteplirsen Study Group and Telethon Foundation DMD Italian Network
Mar 17, 2016·Nucleic Acid Therapeutics·Jeffery A Engelhardt
Jun 28, 2016·Neurology·Luca BelloUNKNOWN CINRG investigators
Aug 16, 2016·Neuropsychiatric Disease and Treatment·Jean K Mah
Mar 11, 2017·Drug Design, Development and Therapy·Kenji Rowel Q LimToshifumi Yokota
Mar 12, 2019·Journal of Neuromuscular Diseases·Navid KhanUNKNOWN Eteplirsen Investigators and the CINRG DNHS Investigators
Feb 7, 2020·Drugs·Young-A Heo
Mar 7, 2020·Neurology·Diane E FrankUNKNOWN SKIP-NMD Study Group
Jun 7, 2020·Orphanet Journal of Rare Diseases·Salvatore CrisafulliGianluca Trifirò
Dec 8, 2020·Annals of Clinical and Translational Neurology·Hirofumi KomakiShinichi Takeda

❮ Previous
Next ❯

Citations

Sep 8, 2021·Advanced Drug Delivery Reviews·Akash GuptaRobert Langer
Nov 14, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Atul Rawat, Brett M Morrison
Nov 20, 2021·Archives of Toxicology·Omar Sheikh, Toshifumi Yokota

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists
© 2021 Meta ULC. All rights reserved