QRL-201 for ALS

Recruiting at14 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: QurAlis Corporation

Disqualifiers: SOD1/FUS gene variants, Other studies, Stem cell/gene therapy, Neurological disorders, others

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.

Will 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.

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. ^{1 2 3 4 5}

Research Team

Angela Genge, MD

Principal Investigator

QurAlis Corporation

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

My condition shows signs of nerve damage affecting muscle movement.

I can undergo a lumbar puncture procedure.

My ALS symptoms started less than 2 years ago.

Exclusion Criteria

Currently enrolled in any other clinical study involving either an investigational product (IP) or off-label use of a drug or device

I have previously received stem cell or gene therapy.

Your lab test results show a significant health problem, as determined by the doctor in charge of the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple-ascending doses of QRL-201 or placebo intrathecally

Approximately 60 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• QRL-201 (Other)

Trial Overview 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.

Participant Groups

Group I: QRL-201: Sporadic ALS Experimental Treatment 1 Intervention

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

Group II: QRL-201: C9orf72-ALS Experimental Treatment 1 Intervention

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

Group III: Placebo: Sporadic ALS Placebo Group 1 Intervention

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

Group IV: Placebo: C9orf72-ALS Placebo Group 1 Intervention

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

QRL-201 is already approved in Canada for the following indications:

Approved in Canada as QRL-201 for:

• Amyotrophic Lateral Sclerosis (Phase 1)

Who Is Running the Clinical Trial?

QurAlis Corporation

Lead Sponsor

Trials

6

Recruited

270+

Findings from Research

In the CENTAUR trial, the combination of oral sodium phenylbutyrate and taurursodiol significantly reduced levels of neuroinflammatory biomarkers YKL-40 and C-reactive protein (CRP) by approximately 20% and 30%, respectively, after 24 weeks compared to placebo.

The reductions in YKL-40 and CRP levels correlated with improved scores on the ALS Functional Rating Scale-Revised (ALSFRS-R), suggesting these biomarkers may serve as treatment-sensitive indicators of disease progression in ALS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sodium phenylbutyrate and taurursodiol on plasma concentrations of neuroinflammatory biomarkers in amyotrophic lateral sclerosis: results from the CENTAUR trial. Bowser, R., An, J., Mehta, L., et al.[2023]

A Delphi panel of 24 ALS healthcare providers in France reached a consensus to adopt the new Gold Coast criteria for diagnosing ALS, replacing the more complex El Escorial criteria, which will streamline clinical practice.

AMX0035, a treatment targeting endoplasmic reticulum stress and mitochondrial dysfunction, is viewed as a promising new option for ALS management, especially when used alongside riluzole, pending confirmation from ongoing phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of amyotrophic lateral sclerosis in clinical practice: Results of the expert consensus using the Delphi methodology. Cassereau, J., Bernard, E., Genestet, S., et al.[2023]

In a phase 2 trial (CENTAUR) involving adults with ALS, the coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly improved survival, with a median overall survival of 25.0 months compared to 18.5 months for the placebo group.

Participants who started treatment with PB-TURSO at baseline experienced a 6.5-month longer median survival, indicating that PB-TURSO not only slows functional decline but also offers survival benefits for ALS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. Paganoni, S., Hendrix, S., Dickson, SP., et al.[2022]

MN-166 (ibudilast) shows promise as a neuroprotective treatment for ALS by inhibiting inflammation and glial cell activation, with early studies indicating potential improvements in survival and disease progression.

The ongoing COMBAT-ALS study, involving a randomized, double-blind, placebo-controlled design, aims to rigorously evaluate the safety, tolerability, and efficacy of MN-166 on various outcomes in ALS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. Oskarsson, B., Maragakis, N., Bedlack, RS., et al.[2022]

A review of 53 new drugs evaluated in clinical trials for ALS from 2020 to 2022 identified five promising candidates, including AMX0035, which has recently been approved by the FDA, marking it as the third drug approved for ALS treatment after riluzole and edaravone.

The review categorized these drugs into eight mechanistic groups, highlighting a diverse range of approaches being explored to combat ALS, with 13 drugs currently in phase 3 trials, indicating ongoing efforts to find more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022. Jiang, J., Wang, Y., Deng, M.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of sodium phenylbutyrate and taurursodiol on plasma concentrations of neuroinflammatory biomarkers in amyotrophic lateral sclerosis: results from the CENTAUR trial. [2023]

2. France pubmed.ncbi.nlm.nih.gov

Management of amyotrophic lateral sclerosis in clinical practice: Results of the expert consensus using the Delphi methodology. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

New developments and opportunities in drugs being trialed for amyotrophic lateral sclerosis from 2020 to 2022. [2022]