A first-in-human dose-escalation study of intrathecal INS1202 gene therapy in adults with amyotrophic lateral sclerosis (ALS)

Topic:

Clinical Trials

Poster Number: 388 O

Author(s):

Mark Stahl, MD, PhD, Insmed Gene Therapy LLC, San Diego, CA, USA, Laura Ferraiuolo, Insmed Gene Therapy LLC, San Diego, CA, USA, Gretchen Thomsen, PhD, Insmed Gene Therapy, Lynn Bayless, Insmed Gene Therapy LLC, San Diego, CA, USA, Paul Chang, MPH, Insmed, Arman Ghorbani, Insmed Gene Therapy LLC, San Diego, CA, USA, Young Jae Jeong, Insmed Gene Therapy LLC, San Diego, CA, USA, Allan Kaspar, PhD, Insmed Gene Therapy LLC, San Diego, CA, USA, Sheritha Lee, PhD, Insmed Gene Therapy, Heather Shahbazian, Insmed Gene Therapy LLC, San Diego, CA, USA, Samit Varma, Insmed Gene Therapy LLC, San Diego, CA, USA, Adebayo Lawal, Insmed Gene Therapy LLC, San Diego, CA, USA, Brian Kaspar, PhD, Insmed, Inc., Nicholas Maragakis, MD, Johns Hopkins School of Medicine, Baltimore, MD, USA

Background

ALS is characterized by progressive degeneration of motor neurons in the brain and spinal cord. Misfolded superoxide dismutase 1 (SOD1) protein aggregates are a pathological hallmark of SOD1-ALS, and misfolded wild-type SOD1 may participate in the pathogenesis of sporadic ALS (sALS). INS1202, a short-hairpin RNA construct delivered via an adeno-associated virus serotype 9 vector, is designed to suppress human SOD1 expression, preventing its toxic accumulation. INS1202 improved muscle function and survival in SOD1-mutant mice and reduced toxicity of sALS patient-derived astrocytes in co-culture with motor neurons. This supports clinical evaluation of whether SOD1 suppression reduces neurotoxicity and slows ALS progression.

Objectives

ARMOR is a first-in-human, multi-center, open-label phase 1 study that will evaluate safety, tolerability, and pharmacodynamics of a single intrathecal dose of INS1202 in adults with ALS. Eligible participants are aged 18–80 years, meet Gold Coast diagnostic criteria, and have an ALS Functional Rating Scale-Revised (ALSFRS-R) score ≥24, disease duration ≤42 months, and predicted vital capacity ≥50%. Participants with sALS require negative testing for known ALS-associated genetic mutations; participants with SOD1-ALS require a confirmed pathogenic SOD1 mutation.

Three sequential dose cohorts are planned. Dose escalation includes a 30-day safety monitoring period between initial patients and between cohorts, with review and endorsement by an independent data monitoring committee. Participants will have a 48-week primary follow-up for safety and exploratory efficacy post-dose, with long-term safety assessed in a 4-year extension study.

The primary endpoint is incidence and severity of adverse events. Secondary endpoints include identification of the recommended phase 2 dose and evaluation of viral vector shedding. Exploratory endpoints include SOD1 and neurofilament light chain protein levels, muscle function tests, patient-reported outcomes, and ALSFRS-R score.

Conclusions

The ARMOR trial is actively recruiting patients.
This study and Amiculum medical writing support are funded by Insmed Incorporated.