Clinical trial NCT05633459: A Study Evaluating the Safety and Tolerability of QRL-201 in ALS
Official title: A Multi-Center, Randomized, Double-Blind Placebo Controlled Multiple-Ascending Dose Study to Evaluate the Safety and Tolerability of QRL-201 in Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS, Stathmin-2, STMN2, ASO, Antisense Oligonucleotide
Lead sponsor: QurAlis Corporation
Sponsor class: INDUSTRY
First posted: 2022-12-01
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the safety and tolerability of multiple doses of QRL-201 in people living with ALS

Detailed description: This first-in-human, Phase 1 study will evaluate the safety, tolerability, and pharmacokinetics (PK) of QRL-201 administered intrathecal (IT) to participants with Amyotrophic Lateral Sclerosis. Two dose escalation cohorts of 8 participants each, followed by an additional 48 participants, receiving the study drug in a 6:2 ratio of QRL-201 to placebo.

Eligibility criteria: Inclusion Criteria:

* Male or female participants aged 18 to 80 years diagnosed with ALS
* ALS symptom onset within 24 months of Screening
* Slow vital capacity \>50%
* Clinical or electrodiagnostic evidence of lower motor neuron involvement
* Not pregnant and not nursing
* Willing and able to practice effective contraception
* Able to tolerate lumbar puncture
* If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion)

Exclusion Criteria:

* Pathogenic variant, likely pathogenic variant, or variant of uncertain significance in the superoxide dismutase 1 (SOD1) and/or fused in sarcoma (FUS) genes
* Currently enrolled in any other clinical study involving either an investigational product (IP) or off-label use of a drug or device
* Prior exposure to stem cell or gene therapy products
* Any contraindication to intrathecal drug administration
* Abnormal laboratory values deemed clinically significant by the Investigator
* Significant infection or known inflammatory process
* Any sign and/or history of neurological conditions and other neuromuscular disorders that could affect the electrophysiological recordings.
* An EEG that shows signs of abnormal electrical activity (e.g., epilepsy)

Primary outcomes:
measure: Number of participants with one or more treatment emergent adverse events and serious adverse events
timeFrame: Baseline through Day 421 [End of Study Visit
Secondary outcomes:
measure: Pharmacokinetics (plasma): Maximum observed concentration of QRL-201 (Cmax)
timeFrame: Predose up to 24 hours post dose
measure: Pharmacokinetics (plasma): Area under the concentration time curve from zero to infinity (AUCinf) of QRL-201
timeFrame: Predose up to 24 hours post dose
measure: Pharmacokinetics (plasma): Time of maximum concentration (Tmax) of QRL-201
timeFrame: Predose up to 24 hours postdose
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven (UZ Leuven)
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Montréal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montréal
country: Canada
facility: Montreal Neurological Institute-Hospital
state: Quebec
city: Bonn
country: Germany
facility: Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE)
state: North Rhine-Westphalia
city: Berlin
country: Germany
facility: Charité Research Organisation
city: Lübeck
country: Germany
facility: University Hospital Schleswig-Holstein (UKSH) Campus Lübeck, Department for Neurology/ Precision Neurology
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Dublin
country: Ireland
facility: St James's Hospital
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: London
country: United Kingdom
facility: Kings College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery
city: Sheffield
country: United Kingdom
facility: The University of Sheffield, Royal Hallamshire Hospital
Study officials:
affiliation: QurAlis Corporation
name: Angela Genge, MD
role: STUDY_DIRECTOR
References: