PXT3003 for Charcot-Marie-Tooth Disease

(PLEO-CMT-FU Trial)

Not currently recruiting at 25 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Pharnext SA

Must not be taking: Opioids, Cancer drugs, others

Disqualifiers: Significant health change, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called PXT3003 for individuals with Charcot-Marie-Tooth Type 1A (CMT1A), a condition affecting the nerves and causing muscle weakness and wasting. The trial evaluates the effectiveness and safety of PXT3003 over an extended period. Participants from an earlier study of this treatment can continue in this trial. Ideal candidates have completed the previous study and have a confirmed diagnosis of CMT1A. As a Phase 3 trial, this is the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications that are not allowed in the study, like baclofen, naltrexone, and some others. It's best to discuss your current medications with the study team to see if any changes are needed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that PXT3003 has been tested for safety in people with Charcot-Marie-Tooth disease type 1A (CMT1A). In earlier studies, most patients who took PXT3003 tolerated it well. This treatment combines three ingredients: baclofen, naltrexone, and D-sorbitol.

In these studies, some participants experienced side effects, but they were mostly mild. The most common were stomach issues, such as an upset stomach or diarrhea. These side effects are usually manageable and don't interfere with most people's daily activities.

Although PXT3003 is still under study, reaching this stage of trials indicates it has shown a reasonable level of safety in earlier research. This suggests that many patients have taken it without serious issues.

Prospective trial participants should discuss any concerns or questions with the research team. They can provide more details about the treatment and what to expect. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for Charcot-Marie-Tooth Disease?

Researchers are excited about PXT3003 for Charcot-Marie-Tooth Disease because it combines three active ingredients: baclofen, naltrexone HCl, and D-sorbitol, which work together to target disease symptoms more comprehensively than current options. Unlike existing treatments that typically address only specific symptoms, PXT3003 has the potential to improve overall nerve function by acting on multiple pathways. Additionally, its liquid oral solution form makes it easy to administer and could enhance patient compliance.

What evidence suggests that PXT3003 might be an effective treatment for Charcot-Marie-Tooth Disease?

Research has shown that PXT3003 could help treat Charcot-Marie-Tooth disease type 1A (CMT1A). In this trial, participants will receive one of two doses of PXT3003. One study found that a high dose of PXT3003 not only stabilized patients' conditions but also improved them. PXT3003 combines three ingredients: baclofen, naltrexone, and D-sorbitol. These work together to affect a protein called PMP22, which plays a significant role in CMT1A. This combination has proven to be safe and well-tolerated. Early results also suggest that PXT3003 may reduce symptoms and improve the quality of life for people with CMT1A. ^{1 2 3 4 6}

Who Is on the Research Team?

Marianne de Visser, MD

Principal Investigator

Academic Medical Center, Amsterdam, Netherlands

Mark Roberts, MD

Principal Investigator

Selor Royal NHS Foundation Trust, Manchester, UK

Florian Thomas, MD PhD

Principal Investigator

Seton Hall-Hackensack-Meridian School of Medicine, Hackensack, USA

Teresa Sevilla, MD

Principal Investigator

Hospital Universitario i Politécnico La F, Valencia, Spain

Shahram Attarian, MD

Principal Investigator

CHU la Timone, Marseille, France

Are You a Good Fit for This Trial?

This trial is for patients with Charcot-Marie-Tooth Disease Type 1A who completed the primary study CLN-PXT3003-02. Participants must agree to birth control use, have finished 15 months of prior treatment, and sign a new consent form. Children aged 16-18 need parental consent. Those with significant health changes or using unauthorized treatments can't join.

Inclusion Criteria

I was in the CLN-PXT3003-02 study, took placebo or dose 1, and completed 15 months including the final visit.

I have signed, or if under 18, my parents and I have both signed the consent form for this study.

Patients whose V6 was performed within 4 weeks before entering the extension study or if not done must have a new baseline visit (VB)

Exclusion Criteria

Any clinically significant change in health status that, in the opinion of the Investigator, would prevent the subject from participating in this study or successfully completing this study

I am not taking any medications that are not allowed in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Period 1

Patients continue on PXT3003 dose 1 or dose 2 for 9 months

9 months

Regular visits as per study protocol

Period 2

All patients continue on twice dose 1 (2X5mL)

15 months

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

What Are the Treatments Tested in This Trial?

Interventions

• PXT3003

Trial Overview The trial tests PXT3003's long-term safety and tolerability in CMT1A patients. It continues from a previous study where participants either received PXT3003 or placebo. Now all receive PXT3003 at varying doses over two periods to assess ongoing effects.

How Is the Trial Designed?

Group I: PXT3003 dose 1 Active Control 1 Intervention

Period 1, PXT3003 : Liquid oral solution (0.6 mg/mL baclofen, 0.07 mg/mL naltrexone HCl and 210 mg/mL D-sorbitol), 5 mL bid (taken morning and evening with food) for 9 consecutive months

Group II: PXT3003 dose 2 Active Control 1 Intervention

Period 1, PXT3003: Liquid oral solution (1.2 mg/mL baclofen, 0.14 mg/mL naltrexone HCl and 420 mg/mL D-sorbitol), 5 mL bid (taken morning and evening with food) for 9 consecutive months Period 2, PXT3003: Liquid oral solution (0.6 mg/mL baclofen, 0.07 mg/mL naltrexone HCl and 210 mg/mL D-sorbitol), 10 mL bid (taken morning and evening with food)

Who Is Running the Clinical Trial?

Pharnext SA

Lead Sponsor

Trials

7

Recruited

4,400+

Pharnext S.C.A.

Lead Sponsor

Trials

7

Recruited

4,400+

Premier Research

Collaborator

Premier Research Group plc

Collaborator

SynteractHCR

Industry Sponsor

Trials

10

Recruited

1,200+

Syneos Health

Collaborator

Trials

181

Recruited

69,600+

Amarex

Collaborator

Trials

1

Recruited

190+

Theradis

Collaborator

Trials

1

Recruited

190+

Premier Research Group plc

Industry Sponsor

Trials

65

Recruited

74,200+

John Ratliff

Premier Research Group plc

Chief Executive Officer since 2024

MBA

Dr. Milena Kanova-Petrova

Premier Research Group plc

Chief Medical Officer since 2024

MD

Synteract HCR (Syneos Health)

Collaborator

Trials

1

Recruited

190+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8520617/

A double-blind, placebo-controlled, randomized trial of ... Overall, high-dose PXT3003 is a promising treatment option for patients with Charcot–Marie–Tooth disease type 1A. Supplementary Information. The ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04762758

NCT04762758 | Phase III Trial Assessing the Efficacy and ... This is an international, multi-center, randomized, double-blind, placebo-controlled, parallel-group, Phase III study of PXT3003 in subjects with CMT1A.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25519680/

An exploratory randomised double-blind and placebo ... This trial confirmed the safety and tolerability of PXT3003. The highest dose (HD) showed consistent evidence of improvement beyond stabilization.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02579759

Study Details | NCT02579759 | Phase III Trial Assessing ... The purpose of this study is to determine whether PXT3003 is effective and safe in the treatment of Charcot-Marie-Tooth disease - Type 1 A (CMT1A).

5. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2023/03/6814-TSID_9130-PXT3003-for-Charcot-Marie-Tooth-Disease-V1.0-MAR2023-NON-CONF.pdf

Health Technology Briefing March 2023 A combination of baclofen, naltrexone and D-sorbitol in low doses (PXT3003) could be effective in treating. CMT1A as each agent interferes with PMP22 expression ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4311411/

PMC - PubMed Central An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with ...