NCT05633459
Active, not recruiting
Phase 1
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
ConditionsAmyotrophic Lateral Sclerosis
Overview
- Phase
- Phase 1
- Intervention
- Multiple ascending doses of QRL-201
- Conditions
- Amyotrophic Lateral Sclerosis
- Sponsor
- QurAlis Corporation
- Enrollment
- 64
- Locations
- 15
- Primary Endpoint
- Number of participants with one or more treatment emergent adverse events and serious adverse events
- Status
- Active, not recruiting
- Last Updated
- 8 months ago
Overview
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.
Investigators
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)
Arms & Interventions
QRL-201: Sporadic ALS
Multiple-ascending doses of QRL-201 will be intrathecally administered to individuals with ALS.
Intervention: Multiple ascending doses of QRL-201
Placebo: Sporadic ALS
Multiple-ascending doses of placebo comparator will be intrathecally administered to individuals with ALS.
Intervention: Multiple ascending doses of Placebo
QRL-201: C9orf72-ALS
QRL-201 will be intrathecally administered to individuals with C9orf72-ALS.
Intervention: QRL-201
Placebo: C9orf72-ALS
Placebo comparator will be intrathecally administered to individuals with C9orf72-ALS.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of participants with one or more treatment emergent adverse events and serious adverse events
Time Frame: Baseline through Day 421 [End of Study Visit
Endpoints: A summary of treatment emergent adverse events, serious adverse events, and other non-serious adverse events, regardless of causality, will be reported in the Reported Adverse Events module.
Secondary Outcomes
- Pharmacokinetics (plasma): Maximum observed concentration of QRL-201 (Cmax)(Predose up to 24 hours post dose)
- Pharmacokinetics (plasma): Time of maximum concentration (Tmax) of QRL-201(Predose up to 24 hours postdose)
- Pharmacokinetics (plasma): Area under the concentration time curve from zero to infinity (AUCinf) of QRL-201(Predose up to 24 hours post dose)
Study Sites (15)
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Related News
Neurology News: ShiraTronics' Migraine Device Trial, QurAlis' ALS Therapy, and Anavex's Alzheimer's Drug Application• ShiraTronics has initiated its RELIEV-CM2 study, implanting its neuromodulation device in chronic migraine patients across the US and Australia to assess therapeutic effects.
• QurAlis' QRL-201, designed to restore STATHMIN-2 expression, advances to the dose range-finding phase of its ANQUR trial for ALS after successful dose-escalation.
• Anavex Life Sciences has submitted a marketing authorization application to the EU for blarcamesine as a potential treatment for Alzheimer's disease, based on Phase 2/3 trial data.QurAlis Advances ALS Programs: QRL-201 Enters Dose Range-Finding, QRL-101 Dosed in Phase 1• QurAlis' QRL-201, designed to restore STMN2 expression, enters the dose range-finding phase of its Phase 1 ANQUR trial after successful dose escalation.
• The ANQUR trial expands to include patients with C9orf72-related ALS and will assess additional biomarkers to evaluate QRL-201's therapeutic potential.
• The first ALS patient has been dosed in a Phase 1 trial of QRL-101, a Kv7.2/7.3 ion channel opener, targeting hyperexcitability-induced disease progression.
• QRL-101's Phase 1 trial will assess safety, tolerability, and impact on nerve cell excitability biomarkers, with topline data expected in the first half of 2025.ALS Clinical Trial Landscape: Investigational Therapies Targeting Sporadic ALS• Several clinical trials are underway for sporadic ALS, targeting TDP-43 pathology, STMN2 expression, and neuroinflammation.
• Biogen's BIIB-105, AbbVie/Calico's ABBV-CLS-7262, Denali's DNL-343, and QurAlis' QRL-201 are among the therapies currently being evaluated in clinical trials.
• Prilenia's Pridopidine and Clene's CNM-Au8 have completed Phase 2 trials, showing some positive trends in motor function and survival benefits, respectively.
• The FDA is set to make a decision on Brainstorm Cell's NurOwn, a mesenchymal stem cell therapy, with an advisory committee meeting scheduled for September 27th.