PTC857 for ALS

(CARDINALS Trial)

No longer recruiting at 74 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: PTC Therapeutics

Must be taking: Riluzole, Edaravone, Sodium phenylbutyrate

Disqualifiers: Pregnancy, Breast cancer, Significant diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called PTC857 for people with ALS, a disease affecting nerve cells in the brain and spinal cord. The trial aims to assess the effectiveness and safety of PTC857 compared to a placebo over 24 weeks. Participants who respond well can continue using PTC857 to monitor long-term effects. The trial seeks participants diagnosed with ALS within the last two years who still have relatively good motor function. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You can continue taking your current medications as long as they have been stable for at least 14 days before the study starts and remain unchanged during the study. However, if you are on standard ALS treatments like riluzole, edaravone, or sodium phenylbutyrate/taurursodiol, they need to be stable for 30 days before the study and remain unchanged.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that PTC857, a treatment under study for ALS (amyotrophic lateral sclerosis), has undergone early human trials. These trials examined how the body processes the drug and assessed its safety. Results suggest that PTC857 is generally well-tolerated. Some adverse events, or side effects, were reported, but they were mostly mild, indicating that while some participants experienced side effects, they were not serious.

Now in Phase 2 trials, the treatment has passed initial safety checks in humans. This phase focuses on evaluating the treatment's effectiveness and continues to monitor its safety. Ongoing testing indicates that PTC857 demonstrated a reasonable level of safety in earlier studies, prompting the enrollment of more participants to further explore its effects. ^{1 2 3 4 5}

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

Most treatments for ALS, like riluzole and edaravone, aim to slow disease progression but aren't highly effective in stopping nerve cell damage. PTC857 is unique because it targets a different pathway, potentially offering a new approach to managing ALS. Researchers are excited about PTC857 as it may provide a more robust way to protect neurons compared to existing options, giving hope for improved outcomes for those living with ALS. Additionally, the treatment includes a long-term extension phase, allowing for extended observation of its effects over time, which is promising for understanding its long-term benefits.

What evidence suggests that PTC857 might be an effective treatment for ALS?

Research suggests that PTC857, also known as utreloxastat, could help treat ALS (amyotrophic lateral sclerosis). This treatment blocks a specific enzyme that may contribute to the disease's progression. Early studies have shown that PTC857 is safe and can be taken as a pill, providing convenience for patients. Although more research is needed to confirm its effectiveness, these initial findings offer hope for people with ALS. During the 24-week treatment period, participants in this trial will receive either PTC857 or a placebo. ^{1 3 4 6 7}

Who Is on the Research Team?

Subha Krishnan

Principal Investigator

PTC Therapeutics

Are You a Good Fit for This Trial?

This trial is for people with ALS who have had symptoms for less than 24 months and a score of at least 34 on the ALSFRS-R scale. They must not be pregnant, nursing, or planning pregnancy, have no significant respiratory issues (slow vital capacity ≥60%), and no recent use of certain ALS treatments together. Participants should not have breast cancer history or be in other studies.

Inclusion Criteria

You have been diagnosed with either definite ALS or probable ALS based on the EL Escorial criteria.

My lung function is good enough to pass a basic breathing test.

You have been diagnosed with ALS within the past 24 months.

Exclusion Criteria

Current participation in any other investigational study with an investigational product or participation within 30 days prior to the start of the Screening Period or 5 half-lives of the previously taken investigational drug, whichever is longer

I have previously been treated with PTC857.

I have had breast cancer or a close family member has.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PTC857 or placebo for 24 weeks

24 weeks

Long-term Extension (LTE)

Participants receive open-label PTC857 for 28 weeks

28 weeks

Continued Long-term Extension

Participants receive open-label PTC857 for an additional 108 weeks

108 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• PTC857

Trial Overview The study tests PTC857's effectiveness and safety against a placebo in treating ALS. Participants will randomly receive either PTC857 or an inactive substance to compare outcomes between the two groups.

How Is the Trial Designed?

Group I: PTC857 Experimental Treatment 1 Intervention

Participants will receive PTC857 during the 24-Week Treatment Period. Following successful completion of the Treatment Period, participants who enter the Long-term Extension (LTE) Period, will receive open-label PTC857 for 28 weeks. Following completion of the LTE period, participants who enter the Continued LTE Period will receive open-label PTC857 for an additional 108 weeks.

Group II: Placebo Active Control 1 Intervention

Participants will receive matching placebo during the 24-Week Treatment Period. Following successful completion of the Treatment Period, participants who enter the LTE Period, will receive open-label PTC857 for 28 weeks. Following completion of the LTE period, participants who enter the Continued LTE Period will receive open-label PTC857 for an additional 108 weeks.

Who Is Running the Clinical Trial?

PTC Therapeutics

Lead Sponsor

Trials

75

Recruited

6,300+

Dr. Matthew B. Klein

PTC Therapeutics

Chief Executive Officer since 2023

BA from the University of Pennsylvania, MD from Yale University School of Medicine, MS in Epidemiology from the University of Washington School of Public Health

Dr. Stuart W. Peltz

PTC Therapeutics

Chief Medical Officer since 2023

MD from Harvard Medical School

Published Research Related to This Trial

The study evaluated design modifications for phase 3 clinical trials in ALS, using data from 988 participants across 5 trials and 5,100 from population-based cohorts, which could reduce sample size by 30.5% and placebo exposure time by 35.4%.

By implementing flexible trial designs and prognostic survival models, the proposed strategies aim to enhance patient selection and minimize exposure to ineffective treatments, potentially leading to more effective ALS therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovating Clinical Trials for Amyotrophic Lateral Sclerosis: Challenging the Established Order. van Eijk, RPA., Nikolakopoulos, S., Roes, KCB., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05349721

NCT05349721 | Study to Assess the Effects of PTC857 ... This study will assess the efficacy and safety of PTC857 treatment in participants diagnosed with ALS.

2. neurology.org neurology.org/doi/10.1212/WNL.0000000000205241

CARDINALS: A Phase 2, Randomized, Double-blind ... Utreloxastat (PTC857) is an emerging, orally bioavailable small molecule for the treatment of ALS that inhibits 15-lipoxygenase (15-LO) enzyme and the ...

3. clinicaltrials.ptcbio.com clinicaltrials.ptcbio.com/trials/PTC857-CNS-001-ALS?

Study to Assess the Effects of PTC857 Treatment in ... This study will assess the efficacy and safety of PTC857 treatment in participants diagnosed with ALS.

4. neals.org neals.org/als-trials/nct05349721

A Phase 2, Randomized, Double-Blind, Placebo ... This study will assess the effects and safety of PTC857 treatment in participants diagnosed with ALS.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10107758/

First‐in‐Human Studies of Pharmacokinetics and Safety of ... Utreloxastat (PTC857) is a 15‐lipoxygenase inhibitor being developed to treat amyotrophic lateral sclerosis. This first‐in‐human study investigated the safety ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36516010/

First-in-Human Studies of Pharmacokinetics and Safety ... Utreloxastat (PTC857) is a 15-lipoxygenase inhibitor being developed to treat amyotrophic lateral sclerosis. This first-in-human study ...

7. accp1.onlinelibrary.wiley.com accp1.onlinelibrary.wiley.com/doi/full/10.1002/cpdd.1203

First‐in‐Human Studies of Pharmacokinetics and Safety of ... Utreloxastat (PTC857) is a 15-lipoxygenase inhibitor being developed to treat amyotrophic lateral sclerosis. This first-in-human study ...