QRL-201 for ALS

Not currently recruiting at 17 trial locations

Overseen By QurAlis Corporation

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: QurAlis Corporation

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 60 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called QRL-201 for people with ALS, a disease affecting nerve cells in the brain and spinal cord. The main goal is to determine the safety of QRL-201 and how well participants can tolerate it. The trial includes different groups: some will receive QRL-201, while others will receive a placebo, a harmless pill resembling the real drug. Individuals diagnosed with ALS within the past two years and who can undergo a lumbar puncture, a procedure to collect fluid from the spine, might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that QRL-201 is likely to be safe for humans?

Research has shown that QRL-201 is under study to determine its safety and tolerability in people with ALS. Early results from a similar study indicated that QRL-201 successfully passed the phase where it was tested at increasing doses. Researchers assessed how the body handles the drug at different amounts to ensure it is safe for people to take more over time.

The treatment is administered intrathecally, meaning it is delivered directly into the spinal fluid. This method targets specific areas more directly. Although QRL-201 is being tested in humans for the first time, no major safety issues have been reported so far.

Since this study is in an early phase, it primarily focuses on how well people can tolerate the treatment. Researchers closely monitor for any side effects. The absence of significant adverse events in the initial stages is a positive sign, but more information is needed as the study continues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ALS?

Researchers are excited about QRL-201 for ALS because it offers a new approach by being administered intrathecally, delivering the treatment directly to the spinal fluid where it can potentially be more effective. Unlike traditional options like Riluzole and Edaravone, which are taken orally or intravenously, QRL-201 may provide a more targeted delivery to the central nervous system. This could mean better outcomes for patients with both sporadic ALS and the genetic C9orf72-ALS variant, as it directly addresses the disease at its source.

What evidence suggests that QRL-201 might be an effective treatment for ALS?

Research has shown that QRL-201 targets a protein called STATHMIN-2, crucial for nerve cell function in ALS. ALS causes nerve cells in the brain and spinal cord to die. Early studies suggest that QRL-201 can increase STATHMIN-2 levels, potentially protecting nerve cells. In this trial, participants with sporadic ALS or C9orf72 ALS will receive QRL-201, while others will receive a placebo. These early findings suggest that QRL-201 could slow ALS progression by supporting nerve cell health, particularly for those with C9orf72 ALS, a specific genetic type of the disease. ^{1 2 3 5 6}

Who Is on the Research Team?

Angela Genge, MD

Principal Investigator

QurAlis Corporation

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• QRL-201

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.

How Is the Trial Designed?

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 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)

Who Is Running the Clinical Trial?

QurAlis Corporation

Lead Sponsor

Trials

6

Recruited

270+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. quralis.com quralis.com/news/quralis-anqur-clinical-trial-of-qrl-201-in-als-advances-to-dose-range-finding-drf-phase-with-first-participant-dosed/

QurAlis' ANQUR Clinical Trial of QRL-201 in ALS ... The Phase 1 ANQUR clinical trial evaluating QRL-201 for the treatment of ALS has successfully completed the dose-escalation phase, based on pharmacokinetic (PK ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05633459

A Study Evaluating the Safety and Tolerability of QRL-201 ... This first-in-human, Phase 1 study will evaluate the safety, tolerability, and pharmacokinetics (PK) of QRL-201 administered intrathecal (IT) to participants ...

3. neurology.org neurology.org/doi/10.1212/WNL.0000000000205187

QRL-201-01—A Multi-center, Randomized, Double-blind ... QRL-201-01 is a double-blind, multiple-ascending dose study in which approximately 64 people living with ALS will receive QRL-201, or matching placebo, in a 6: ...

4. neurologylive.com neurologylive.com/view/stathmin-targeting-therapy-qrl-201-enters-dose-range-finding-phase-successful-pk-analysis

STATHMIN-Targeting Therapy QRL-201 Enters Dose ... QRL-201 progresses to dose range-finding phase in ANQUR trial, targeting STATHMIN-2 expression in ALS patients, including C9orf72-related ALS.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12010636/

Genetic ALS caused by hexanucleotide repeat expansions in ... Polymorphic GGGGCC hexanucleotide repeat expansions in C9orf72 are a common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia ( ...

6. ctv.veeva.com ctv.veeva.com/study/a-study-evaluating-the-safety-and-tolerability-of-qrl-201-in-als

A Study Evaluating the Safety and Tolerability of QRL-201 in ... The primary objective of this study is to determine the safety and tolerability of multiple doses of QRL-201 in people living with ALS.