A Study Evaluating the Safety and Tolerability of QRL-201 in ALS

NCT05633459 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: QRL-201-01
• Study Type: interventional
• Target: 69
• Locations: 6 countries
• Sites: 15

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

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALS, Stathmin-2, STMN2, ASO, Antisense Oligonucleotide

Outcome Measures

Primary Outcomes (1)

• Number of participants with one or more treatment emergent adverse events and serious adverse events

  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.

  Baseline through Day 421 [End of Study Visit

Secondary Outcomes (3)

• Pharmacokinetics (plasma): Maximum observed concentration of QRL-201 (Cmax)

  Predose up to 24 hours post dose

• Pharmacokinetics (plasma): Area under the concentration time curve from zero to infinity (AUCinf) of QRL-201

  Predose up to 24 hours post dose

• Pharmacokinetics (plasma): Time of maximum concentration (Tmax) of QRL-201

  Predose up to 24 hours postdose

Study Arms (5)

QRL-201: Sporadic ALS

EXPERIMENTAL

Multiple-ascending doses of QRL-201 will be intrathecally administered to individuals with ALS.

Drug: Multiple ascending doses of QRL-201

Placebo: Sporadic ALS

PLACEBO COMPARATOR

Multiple-ascending doses of placebo comparator will be intrathecally administered to individuals with ALS.

Drug: Multiple ascending doses of Placebo

QRL-201: C9orf72-ALS

EXPERIMENTAL

QRL-201 will be intrathecally administered to individuals with C9orf72-ALS.

Drug: QRL-201

Placebo: C9orf72-ALS

PLACEBO COMPARATOR

Placebo comparator will be intrathecally administered to individuals with C9orf72-ALS.

Drug: Placebo

QRL-201: Open-label Extended Dosing Period

EXPERIMENTAL

Open-label QRL-201 will be intrathecally administered to individuals with ALS who qualify for and enter the open-label extended dosing period.

Drug: QRL-201

Interventions

Multiple ascending doses of QRL-201 DRUG

Multiple ascending doses of QRL-201 will be intrathecally administered to individuals with sporadic ALS.

QRL-201: Sporadic ALS

Multiple ascending doses of Placebo DRUG

Multiple ascending doses of placebo comparator will be intrathecally administered to individuals with sporadic ALS.

Placebo: Sporadic ALS

QRL-201 DRUG

QRL-201 will be intrathecally administered to individuals with C9orf72 ALS.

QRL-201: C9orf72-ALS

Placebo DRUG

Placebo comparator will be intrathecally administered to individuals with C9orf72 ALS.

Placebo: C9orf72-ALS

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)
• Male or female participants in the sporadic ALS and C9orf72 ALS Cohorts of QRL-201-01 who have completed through at least Day 253 of safety follow up in the double-blind study period OR have completed Cohort 1 of Cohort 2
• Not pregnant and not nursing
• Willing and able to practice effective contraception
• Can visit study site for required visits
• 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)
• Currently enrolled in any other clinical study involving either an investigational product (IP) or off label use of a drug or device

Sponsors & Collaborators

• QurAlis Corporation: lead

Study Sites (15)

Universitaire Ziekenhuizen Leuven (UZ Leuven)

Leuven, B-3000, Belgium

Location

University of Calgary

Calgary, Alberta, T2N 1N4, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2G3, Canada

Location

Sunnybrook Health Science Centre

Toronto, Ontario, M4N 3M5, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Montreal Neurological Institute-Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE)

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Charité Research Organisation

Berlin, 10117, Germany

Location

University Hospital Schleswig-Holstein (UKSH) Campus Lübeck, Department for Neurology/ Precision Neurology

Lübeck, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

St James's Hospital

Dublin, D08 A978, Ireland

Location

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands

Location

The University of Sheffield, Royal Hallamshire Hospital

Sheffield, United Kingdom, S10 2JF, United Kingdom

Location

Kings College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

National Hospital for Neurology and Neurosurgery

London, WC1N 3BG, United Kingdom

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Manoj Malhotra, MD

  QurAlis Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Multiple-ascending doses of QRL-201 or placebo will be administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: December 1, 2022
• Study Start: December 16, 2022
• Primary Completion: May 29, 2026
• Study Completion (Estimated): November 30, 2027
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); GB (3); BE (1); CA (5); DE (4); IE (1)