QRL-201 for ALS
Recruiting in Palo Alto (17 mi)
+13 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: QurAlis Corporation
Approved in 4 jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests the safety and tolerability of QRL-201, a new drug, in people with ALS. The drug is given directly into the spinal fluid to better reach the nervous system.
How is the drug QRL-201 different from other ALS drugs?
QRL-201 is unique because it is a new treatment being tested for ALS, while existing drugs like riluzole and edaravone only extend survival by a few months. The research does not provide specific details about QRL-201's mechanism or effects, but it is part of ongoing efforts to find more effective treatments for ALS.
12345Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but if you are on approved ALS treatments, you must be on a stable dose during the study.
Eligibility Criteria
This trial is for adults aged 18-80 with ALS, who have had symptoms start within the last 2 years. They must be able to perform a breathing test and not be on varying doses of ALS therapies. Participants should not be pregnant or nursing, can undergo spinal taps, and must use contraception.Inclusion Criteria
I can undergo a lumbar puncture procedure.
My condition shows signs of nerve damage affecting muscle movement.
I am between 18 and 80 years old and have been diagnosed with ALS.
Exclusion Criteria
I have previously received stem cell or gene therapy.
I have a genetic variant in the SOD1 or FUS genes.
I have a significant infection or an ongoing inflammatory condition.
I cannot receive medications directly into my spinal canal.
Participant Groups
The study tests the safety of different doses of QRL-201 in people with ALS. It involves multiple levels of dosing to find out which is safest and most tolerable for patients.
4Treatment groups
Experimental Treatment
Placebo Group
Group I: QRL-201: Sporadic ALSExperimental Treatment1 Intervention
Multiple-ascending doses of QRL-201 will be intrathecally administered to individuals with ALS.
Group II: QRL-201: C9orf72-ALSExperimental Treatment1 Intervention
QRL-201 will be intrathecally administered to individuals with C9orf72-ALS.
Group III: Placebo: Sporadic ALSPlacebo Group1 Intervention
Multiple-ascending doses of placebo comparator will be intrathecally administered to individuals with ALS.
Group IV: Placebo: C9orf72-ALSPlacebo Group1 Intervention
Placebo comparator will be intrathecally administered to individuals with C9orf72-ALS.
QRL-201 is already approved in European Union, United States, Canada, United Kingdom for the following indications:
🇪🇺 Approved in European Union as QRL-201 for:
- Amyotrophic Lateral Sclerosis (Phase 1)
🇺🇸 Approved in United States as QRL-201 for:
- Amyotrophic Lateral Sclerosis (Phase 1)
🇨🇦 Approved in Canada as QRL-201 for:
- Amyotrophic Lateral Sclerosis (Phase 1)
🇬🇧 Approved in United Kingdom as QRL-201 for:
- Amyotrophic Lateral Sclerosis (Phase 1)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of CalgaryCalgary, Canada
University of AlbertaEdmonton, Canada
CHUM - Hopital Notre-Dame, 1560 Sherbrooke St EMontréal, Canada
Montreal Neurological Institute-HospitalMontréal, Canada
More Trial Locations
Loading ...
Who is running the clinical trial?
QurAlis CorporationLead Sponsor
References
Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. [2022]An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS.
MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. [2022]Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with motor neuron loss as a defining feature. Despite significant effort, therapeutic breakthroughs have been modest. MN-166 (ibudilast) has demonstrated neuroprotective action by various mechanisms: inhibition of proinflammatory cytokines and macrophage migration inhibitory factor, phosphodiesterase inhibition, and attenuation of glial cell activation in models of ALS. Early-phase studies suggest that MN-166 may improve survival outcomes and slow disease progression in patients with ALS. This article describes the rationale and design of COMBAT-ALS, an ongoing randomized, double-blind, placebo-controlled, multicenter Phase IIb/III study in ALS. This study is designed to evaluate the pharmacokinetics, safety and tolerability and assess the efficacy of MN-166 on function, muscle strength, quality of life and survival in ALS.
New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022. [2022]Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that primarily affects motor neurons in the brain and spinal cord. In the recent past, there have been just two drugs approved for treatment, riluzole and edaravone, which only prolong survival by a few months. However, there are many novel experimental drugs in development. In this review, we summarize 53 new drugs that have been evaluated in clinical trials from 2020 to 2022, which we have classified into eight mechanistic groups (anti-apoptotic, anti-inflammatory, anti-excitotoxicity, regulated integrated stress response, neurotrophic factors and neuroprotection, anti-aggregation, gene therapy and other). Six were tested in phase 1 studies, 31 were in phase 2 studies, three failed in phase 3 studies and stopped further development, and the remaining 13 drugs were being tested in phase 3 studies, including methylcobalamin, masitinib, MN-166, verdiperstat, memantine, AMX0035, trazodone, CNM-Au8, pridopidine, SLS-005, IONN363, tofersen, and reldesemtiv. Among them, five drugs, including methylcobalamin, masitinib, AMX0035, CNM-Au8, and tofersen, have shown potent therapeutic effects in clinical trials. Recently, AMX0035 has been the third medicine approved by the FDA for the treatment of ALS after riluzole and edaravone.
Management of amyotrophic lateral sclerosis in clinical practice: Results of the expert consensus using the Delphi methodology. [2023]Amyotrophic lateral sclerosis (ALS) is a rare disease characterized by a progressive and irreversible degeneration of upper and lower motor neurons leading to death. In France, limited data exist describing the criteria used in clinical practice for diagnosis and follow-up, and how novel therapies may fit in. The objective of this Delphi panel was to obtain an overview of current French practices in ALS diagnosis, management, and follow-up by determining the scales and criteria used in clinical practice outside of clinical trials, as well as the place of a future treatment like AMX0035, acting on endoplasmic reticulum (ER) stress and mitochondrial dysfunction, in the current therapeutic strategies. A questionnaire was administered to 24 ALS healthcare providers practicing in ALS centers in France. Two rounds of remote voting were organized, before proposition of final consensus statements. Consensus was considered reached when at least 66% of the voters agreed. Consensus were obtained to define the new Gold Coast criteria as the ones used in clinical practice to establish the diagnosis of ALS, thus replacing the revised El Escorial criteria, considered too complex and now mainly used to characterize the patient populations to be included in clinical trials. The clinical factors considered to establish ALS diagnosis are mainly the demonstration of progression of the motor deficit and elimination of differential diagnoses. The ALSFRS-R scale is used in daily clinical practice to assess patient's functional impairment in terms of number of points lost, with the bulbar, respiratory, and fine motor subscores being the most important to evaluate independently. A critical medical need was identified regarding the provision of new therapeutic alternatives in ALS. The panel members would support the earliest management of patients. In this landscape, based on data from a very encouraging phase II (Centaur trial), AMX0035 represents a new tool of choice in current treatment strategies for all patients for whom experts are confident in the diagnosis of ALS, in combination with riluzole. These results will need to be confirmed by the ongoing phase III trial (Phoenix trial).
Effect of sodium phenylbutyrate and taurursodiol on plasma concentrations of neuroinflammatory biomarkers in amyotrophic lateral sclerosis: results from the CENTAUR trial. [2023]An oral sodium phenylbutyrate and taurursodiol combination (PB and TURSO) significantly reduced functional decline in people living with amyotrophic lateral sclerosis (ALS) in the CENTAUR trial. Biomarkers linking clinical therapeutic effect with biological changes are of high interest in ALS. We performed analyses of neuroinflammatory biomarkers associated with ALS in the literature, including YKL-40 (also known as chitinase-3-like protein 1), chitinase 1 (CHIT1) and C reactive protein (CRP), in plasma samples collected in CENTAUR.