PIPE-307 for Multiple Sclerosis

(VISTA Trial)

Recruiting at 26 trial locations

Overseen By

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Pipeline Therapeutics, Inc.

Must be taking: Immunomodulatory DMT

Must not be taking: Anticholinergics, CYP3A4 modulators

Disqualifiers: Optic neuritis, Severe myopia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

168 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called PIPE-307 to see if it can help people with relapsing-remitting multiple sclerosis. The drug likely works by calming the immune system to prevent nerve damage. The study will compare two different doses of PIPE-307 over several months.

Do I need to stop my current medications to join the trial?

The trial requires stopping certain medications. You cannot use dalfampridine, 4-aminopyridine drugs, anticholinergic medications, or drugs affecting CYP3A4 enzyme activity within 30 days before or during the study. Check with the trial team for specifics on your current medications.

Will I have to stop taking my current medications?

The trial requires that you do not use certain medications, such as dalfampridine, anticholinergic medications, and drugs affecting the CYP3A4 enzyme, within 30 days before and during the study. If you are on these medications, you may need to stop taking them to participate.

What data supports the idea that PIPE-307 for Multiple Sclerosis is an effective drug?

The available research does not provide specific data on the effectiveness of PIPE-307 for Multiple Sclerosis. The articles focus on other treatments and general aspects of managing the condition, such as patient satisfaction with support programs and outcomes of other therapies. Without direct evidence or comparisons involving PIPE-307, we cannot conclude its effectiveness from the provided information. ^{1 2 3 4 5}

What safety data is available for PIPE-307 in treating Multiple Sclerosis?

The provided research does not specifically mention PIPE-307 or its safety data. However, it discusses the importance of pharmacovigilance and registry-based studies in assessing the safety of multiple sclerosis treatments. Studies like REGIMS, Optimise:MS, and FASM focus on monitoring adverse effects and safety profiles of disease-modifying therapies for MS, highlighting the need for continuous safety evaluation of new treatments. ^{6 7 8 9 10}

Is the drug PIPE-307 a promising treatment for Multiple Sclerosis?

The information provided does not mention PIPE-307, so we can't determine if it's a promising treatment for Multiple Sclerosis based on this data. ^{11 12 13 14 15}

How is the drug PIPE-307 different from other multiple sclerosis drugs?

PIPE-307 is unique because it may offer a novel mechanism of action or administration compared to existing oral treatments like fingolimod and siponimod, which are known to modulate immune responses in multiple sclerosis. ^{11 12 13 14 15}

Research Team

Stephen Huhn, MD

Principal Investigator

Contineum Therapeutics

Eligibility Criteria

This trial is for English-speaking adults aged 18 to 50 with relapsing-remitting multiple sclerosis, as per the Revised McDonald Criteria. Participants must have been on a stable dose of one MS drug for the past six months and agree to use effective contraception. They should be in good health aside from MS.

Inclusion Criteria

I agree to use effective birth control during and for 1 month after the study.

Your disability status and retinal nerve fiber layer meet specific criteria.

I have been on one stable MS treatment for the past 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive PIPE-307 or placebo for 26 weeks

26 weeks

Periodic visits for safety assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PIPE-307

Trial Overview The study tests PIPE-307 at two different doses against a placebo in people with relapsing-remitting multiple sclerosis. It's randomized and double-blind, meaning neither participants nor researchers know who gets which treatment, divided into three groups equally over about 30 weeks.

Participant Groups

Group I: PIPE-307 Dose B Experimental Treatment 1 Intervention

Group II: PIPE-307 Dose A Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Pipeline Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

330+

Contineum Therapeutics

Lead Sponsor

Trials

7

Recruited

400+

Findings from Research

A survey of 1,123 adult MS patients revealed that those with greater needs and lower health status utilize patient support programs (PSPs) more, indicating that PSPs are crucial for patients with varying disease severity.

Patients reported that their health status would significantly decline (by 15 points) if the PSP were unavailable, highlighting that these programs provide substantial benefits to health-related quality of life for MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of a patient support program for multiple sclerosis on patient satisfaction and subjective health status. Kohlmann, T., Wang, C., Lipinski, J., et al.[2022]

In a study of 426 multiple sclerosis patients over an average of 8.3 years, it was found that newer treatments like natalizumab and fingolimod significantly reduced the risk of relapses and progression to higher disability levels (EDSS 4 or higher).

Despite an increase in the use of disease-modifying treatments from 31% in 2008 to 52% in 2015, overall healthcare costs remained stable, suggesting that these newer therapies may improve patient outcomes without increasing costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Outcome in Multiple Sclerosis in the Czech Republic. Kobelt, G., Jönsson, L., Pavelcova, M., et al.[2022]

A survey of 46 physicians across Europe revealed that 43% viewed the benefit-risk ratio of ofatumumab for treating relapsing multiple sclerosis as very good, indicating a positive perception of its safety and efficacy.

Over 93% of physicians supported the idea of self-administration of ofatumumab at home, with 83% believing it significantly reduces the time burden for patients, highlighting its convenience as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the treating physicians' first-hand experience with handling and satisfaction of ofatumumab therapy: findings from the PERITIA survey conducted in Europe. Rau, D., Eichau, S., Borriello, G., et al.[2023]

In a study of 65 patients with secondary progressive multiple sclerosis (SPMS), physical patient-reported outcomes (PROs) correlated well with physical disability measures, suggesting that these PROs can serve as useful clinical endpoints for assessing mobility and function.

However, psychological PROs did not correlate with cognitive outcomes or disease burden, indicating they may be better suited for measuring mental quality of life rather than cognitive status in SPMS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient reported outcomes in a secondary progressive MS cohort related to cognition, MRI and physical outcomes. Theodorsdottir, A., Nielsen, HH., Ravnborg, MH., et al.[2023]

The quality of clinical trials for Multiple Sclerosis (MS) treatments is improving due to better standards and regulatory requirements, leading to more effective testing of new compounds.

Despite advancements, selecting appropriate outcome measures remains challenging; it is recommended to use multiple assessment tools to capture the full range of treatment effects on patient disability and relapse rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reconsidering clinical outcomes in Multiple Sclerosis: relapses, impairment, disability and beyond. D'Souza, M., Kappos, L., Czaplinski, A.[2019]

The REGIMS registry is a multicenter observational study in Germany that collects data on the side effects of immunotherapies for multiple sclerosis, providing valuable insights into the long-term safety of these treatments.

By the end of 2019, REGIMS had recruited 1000 patients, primarily women with relapse-remitting MS, demonstrating the registry's ability to gather high-quality, real-world data despite facing logistical challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chances and Challenges of Registry-Based Pharmacovigilance in Multiple Sclerosis: Lessons Learnt from the Implementation of the Multicenter REGIMS Registry. Simbrich, A., Thibaut, J., Khil, L., et al.[2022]

Over the past five years, the treatment options for multiple sclerosis (MS) have expanded significantly, with the approval of new oral medications and a monoclonal antibody, allowing for more personalized treatment strategies.

While these new therapies offer improved management of MS, they also come with rare but serious side effects, highlighting the need for ongoing monitoring and adherence to safety protocols in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current immunotherapy of multiple sclerosis]. Paul, F., Ruprecht, K.[2018]

The Optimise:MS study has recruited over 2,000 participants from 14 hospitals in the UK to assess the safety profile of disease-modifying therapies (DMTs) for multiple sclerosis (MS) in real-world settings, focusing on serious adverse events (SAEs).

The study's statistical analysis plan is designed to address complex confounding factors and will provide valuable insights into the long-term outcomes of DMTs, including the effects of treatment switching and pregnancy outcomes, which are often not covered in randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and Opportunities of Real-World Data: Statistical Analysis Plan for the Optimise:MS Multicenter Prospective Cohort Pharmacovigilance Study. Waddingham, E., Miller, A., Dobson, R., et al.[2022]

In a study involving 272 Individual Case Safety Reports (ICSRs) collected from multiple sclerosis centers, adverse drug reactions (ADRs) were primarily reported in adult patients, with a higher incidence in women, indicating a need for gender-specific considerations in treatment.

Dimethyl fumarate, fingolimod, and IFN beta 1a were the most commonly implicated medications in ADRs, with a median time to event of 177 days for dimethyl fumarate, suggesting that monitoring for side effects should be prioritized during this period after starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary Results of the FASM Study, an On-Going Italian Active Pharmacovigilance Project. Maniscalco, GT., Brescia Morra, V., Florio, C., et al.[2020]

A variety of immunomodulatory and immunosuppressant therapies for multiple sclerosis (MS) have been developed since the 1990s, showing positive effects on relapse rates and disease progression, but they come with significant side effects that require careful monitoring.

Understanding the safety profiles and potential adverse reactions of these therapies is crucial for healthcare providers, as some side effects can be severe or life-threatening, highlighting the importance of patient education and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing Risks with Immune Therapies in Multiple Sclerosis. Förster, M., Küry, P., Aktas, O., et al.[2020]

In a study of 281 patients with relapsing multiple sclerosis, fingolimod significantly reduced the number of MRI-detected lesions and the annual relapse rate compared to placebo, indicating its efficacy as a treatment option.

While fingolimod showed promising results, it was associated with some adverse effects, including elevated liver enzymes and a case of posterior reversible encephalopathy syndrome, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral fingolimod (FTY720) for relapsing multiple sclerosis. Kappos, L., Antel, J., Comi, G., et al.[2022]

In a Phase II study involving 123 patients with relapsing forms of multiple sclerosis (MS), teriflunomide was found to be well tolerated as an add-on therapy to glatiramer acetate, with low rates of adverse events leading to treatment discontinuation.

Teriflunomide significantly reduced MRI markers of disease activity, showing a 64% relative reduction in T1-Gd lesions at the 7 mg dose compared to placebo, indicating its potential efficacy in managing MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis. Freedman, MS., Wolinsky, JS., Truffinet, P., et al.[2020]

Siponimod, an oral medication for multiple sclerosis, has been shown to enhance remyelination in mouse models, indicating its potential to repair damaged nerve fibers.

The treatment demonstrated a bell-shaped dose-response effect, where both low and high doses were effective, but high doses were less efficient, suggesting an optimal concentration for therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Remyelination and Proregenerative Microglia Under Siponimod Therapy in Mechanistic Models. Dietrich, M., Hecker, C., Martin, E., et al.[2022]

In a study of 171 Japanese patients with relapsing multiple sclerosis, fingolimod showed significant efficacy, with 70% of patients on the 0.5 mg dose and 86% on the 1.25 mg dose free from gadolinium-enhanced lesions at six months, compared to only 40% in the placebo group.

While fingolimod was effective, some patients experienced adverse effects such as transient bradycardia and elevated liver enzymes, highlighting the need for monitoring during treatment initiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, controlled trial of fingolimod (FTY720) in Japanese patients with multiple sclerosis. Saida, T., Kikuchi, S., Itoyama, Y., et al.[2022]

Fingolimod, the first oral treatment for relapsing multiple sclerosis, works by blocking sphingosine 1-phosphate receptors, which leads to a selective and reversible reduction in certain lymphocytes, helping to manage the disease without significantly increasing the risk of infections.

While fingolimod does not appear to raise the overall risk of opportunistic infections compared to other treatments, there have been cases of severe herpetic infections, indicating that monitoring for herpesvirus infections is important for patients on this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Infections and fingolimod]. Cervera, C.[2017]

References

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

The impact of a patient support program for multiple sclerosis on patient satisfaction and subjective health status. [2022]

2. Egypt pubmed.ncbi.nlm.nih.gov

Real-Life Outcome in Multiple Sclerosis in the Czech Republic. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Assessment of the treating physicians' first-hand experience with handling and satisfaction of ofatumumab therapy: findings from the PERITIA survey conducted in Europe. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Patient reported outcomes in a secondary progressive MS cohort related to cognition, MRI and physical outcomes. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Reconsidering clinical outcomes in Multiple Sclerosis: relapses, impairment, disability and beyond. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Chances and Challenges of Registry-Based Pharmacovigilance in Multiple Sclerosis: Lessons Learnt from the Implementation of the Multicenter REGIMS Registry. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

[Current immunotherapy of multiple sclerosis]. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Challenges and Opportunities of Real-World Data: Statistical Analysis Plan for the Optimise:MS Multicenter Prospective Cohort Pharmacovigilance Study. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Preliminary Results of the FASM Study, an On-Going Italian Active Pharmacovigilance Project. [2020]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Managing Risks with Immune Therapies in Multiple Sclerosis. [2020]

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

Oral fingolimod (FTY720) for relapsing multiple sclerosis. [2022]

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

A randomized trial of teriflunomide added to glatiramer acetate in relapsing multiple sclerosis. [2020]

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

Increased Remyelination and Proregenerative Microglia Under Siponimod Therapy in Mechanistic Models. [2022]

14. England pubmed.ncbi.nlm.nih.gov

A randomized, controlled trial of fingolimod (FTY720) in Japanese patients with multiple sclerosis. [2022]

15. Spain pubmed.ncbi.nlm.nih.gov

[Infections and fingolimod]. [2017]