ION717 for Prion Diseases

Recruiting at 15 trial locations

Overseen By Ionis Pharmaceuticals, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ionis Pharmaceuticals, Inc.

Disqualifiers: Hydrocephalus, Brain disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 30 weeks

56 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves injecting a drug called ION717 into the spinal fluid of people with prion disease. The goal is to see how the drug behaves in the body and its effects on the disease. Prion disease has few treatment options, making this study important.

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

The trial protocol does not specify whether you need to stop taking your current medications.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the idea that ION717 for Prion Diseases is an effective treatment?

The available research does not provide any data on the effectiveness of ION717 for Prion Diseases. The studies listed focus on other treatments and conditions, such as psoriatic arthritis and cholesterol management, without mentioning ION717 or Prion Diseases. ^{1 2 3 4 5}

What safety data exists for ION717 treatment for Prion Diseases?

The provided research does not contain specific safety data for ION717 or its evaluation under different names. The studies focus on ionizable lipid nanoparticles and their safety in RNA delivery, but do not mention ION717 or its application in prion diseases. ^{6 7 8 9 10}

Is the drug ION717 a promising treatment for prion diseases?

The information provided does not directly mention ION717 or its effectiveness as a treatment for prion diseases. Therefore, we cannot determine if ION717 is a promising treatment based on the given research articles. ^{11 12 13 14 15}

How does the drug ION717 differ from other treatments for prion diseases?

ION717 is unique because prion diseases currently have no standard treatments, making any new drug like ION717 potentially novel in its approach to addressing these conditions. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for adults over 18 with early-stage prion disease, confirmed as probable or definite. Participants need to commit to the study schedule and travel requirements. They must have a caregiver willing to support their involvement throughout the trial.

Inclusion Criteria

I am willing to follow all study requirements, including traveling.

I am 18 years old or older.

I have been diagnosed with prion disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

up to 6 weeks

Treatment

Participants receive multiple doses of ION717 and placebo during the 30-week double-blind treatment period

30 weeks

Open-label extension

Participants receive multiple doses of ION717 during the 70-week open-label extension period

70 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

32 weeks

Treatment Details

Interventions

• ION717

Trial Overview The study is testing ION717, delivered directly into the spinal fluid (intrathecal delivery), against a placebo. It aims to assess how safe it is, how well tolerated by patients, its movement in the body (pharmacokinetics), and its effects on prion disease (pharmacodynamics).

Participant Groups

Group I: ION717 + Placebo, Regimen 2 Experimental Treatment 2 Interventions

Participants will receive multiple doses of study drug (ION717 and placebo) during the 30-week double-blind treatment period; the order of doses is blinded. Participants will then receive multiple doses of ION717 during the 70-week open-label extension period.

Group II: ION717 + Placebo, Regimen 1 Experimental Treatment 2 Interventions

Participants will receive multiple doses of study drug (ION717 and placebo) during the 30-week double-blind treatment period; the order of doses is blinded. Participants will then receive multiple doses of ION717 during the 70-week open-label extension period.

Who Is Running the Clinical Trial?

Ionis Pharmaceuticals, Inc.

Lead Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Findings from Research

In a 156-week phase III study involving 417 patients with psoriatic arthritis (PsA), ixekizumab demonstrated a consistent safety profile with treatment-emergent adverse events occurring in 38% of patients, similar to other treatments.

Efficacy results showed that ixekizumab maintained significant improvements in PsA symptoms and low rates of radiographic progression, with response rates for ACR ≥20% at 62.5% for the every 2 weeks dosing and 69.8% for the every 4 weeks dosing by week 156.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixekizumab treatment of biologic-naïve patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1). Chandran, V., van der Heijde, D., Fleischmann, RM., et al.[2021]

A systematic review of 10 randomized controlled trials with 4198 participants found that PCSK9 monoclonal antibodies (PCSK9-mAbs) had a minimal effect on reducing high-sensitivity C-reactive protein (hs-CRP) levels, with a change of -0.04 mg/L that was not statistically significant.

The analysis indicated that PCSK9-mAbs did not significantly impact hs-CRP levels regardless of the type of antibody used, treatment duration, or participant characteristics, suggesting that their primary benefit may not involve reducing inflammation as measured by hs-CRP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials. Cao, YX., Li, S., Liu, HH., et al.[2019]

In a study involving 2181 patients over 24-104 weeks, most patients (73.7%) on alirocumab 75 mg Q2W plus statins reached LDL cholesterol (LDL-C) goals by week 8.

For the 26.3% of patients who had their dose increased to 150 mg Q2W, 60.9% achieved LDL-C goals by week 24, along with an additional 14.2% reduction in LDL-C, indicating effective dose-response management without increased adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of alirocumab dose increase on LDL lowering and lipid goal attainment in patients with dyslipidemia. Kastelein, JJ., Kereiakes, DJ., Cannon, CP., et al.[2019]

PCSK9 inhibitors are effective in significantly lowering LDL cholesterol levels, especially in patients who do not achieve satisfactory results with statins alone, highlighting their role in managing high cardiovascular risk.

Recent large-scale clinical trials have shown that PCSK9 monoclonal antibodies not only lower cholesterol but also reduce the rates of cardiovascular events, indicating their potential as a critical treatment option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The New Face of Hyperlipidemia and the Role of PCSK9 Inhibitors. Nicholls, SJ.[2021]

In a phase I study involving 133 hypercholesterolemic subjects, RN317 was found to be well tolerated with no treatment-related discontinuations, demonstrating its safety profile.

RN317 effectively reduced LDL cholesterol levels by up to 52.5% after a single dose, and sustained reductions of approximately 50% were observed with multiple doses over an 85-day period, indicating its efficacy in managing cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Randomized Study of a Specifically Engineered, pH-Sensitive PCSK9 Inhibitor RN317 (PF-05335810) in Hypercholesterolemic Subjects on Statin Therapy. Levisetti, M., Joh, T., Wan, H., et al.[2021]

The novel ionizable lipid nanoparticle (244cis) demonstrated enhanced protein expression of human erythropoietin while significantly reducing immunogenicity compared to conventional lipid nanoparticles, making it safer for therapeutic use.

In a study involving tdTomato transgenic mice with pulmonary fibrosis, 244cis LNP achieved high levels of transfection in lung endothelial cells and fibroblasts, indicating its potential for effective mRNA delivery in chronic lung diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety. Kim, M., Jeong, M., Lee, G., et al.[2023]

Lipid nanoparticles (LNPs) containing ALC-0315 demonstrated significantly greater efficacy in knocking down coagulation factor VII and ADAMTS13 in liver cells compared to those containing MC3, achieving up to 10-fold greater knockdown at a dose of 1 mg/kg in mice.

However, at a higher dose of 5 mg/kg, ALC-0315 LNPs showed increased liver toxicity markers, while MC3 LNPs did not, suggesting that while ALC-0315 is more effective, it may pose a risk of hepatotoxicity at elevated doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of DLin-MC3-DMA and ALC-0315 for siRNA Delivery to Hepatocytes and Hepatic Stellate Cells. Ferraresso, F., Strilchuk, AW., Juang, LJ., et al.[2023]

Ionizable lipids are essential for the effective delivery of mRNA in lipid nanoparticle (LNP) formulations, as demonstrated by the FDA approval of the first siRNA drug and two COVID-19 vaccines that utilized unique ionizable lipids.

The review highlights recent advancements in the design and function of ionizable lipids, emphasizing their critical role in enhancing the efficiency of RNA delivery systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rational design and combinatorial chemistry of ionizable lipids for RNA delivery. Xu, Y., Golubovic, A., Xu, S., et al.[2023]

Solid-contact ion-selective electrodes (SC-ISEs) made with different silicones showed excellent performance in detecting potassium ions, maintaining stable responses and selectivity even after 41 hours in porcine plasma, indicating their potential for use in physiological samples.

Among the tested silicones, the commercial silicone (Dow 3140) demonstrated the lowest signal drift in porcine plasma, suggesting it may be the most effective material for long-term applications in wearable sensors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of the Composition of Plasticizer-Free Silicone-Based Ion-Selective Membranes on Signal Stability in Aqueous and Blood Plasma Samples. Spindler, BD., Graf, KI., Dong, XIN., et al.[2023]

Incorporating propyl sulphonate groups into a polytetramethylene oxide-based polyurethane improved its mechanical properties and significantly reduced platelet deposition during short blood-contacting times, indicating better biocompatibility.

The presence of propyl sulphonate was more influential on the polymer's blood-contacting response than ethyl carboxylate, as it enhanced fibrinogen deposition while reducing platelet activation, suggesting potential for safer medical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of carboxylate and/or sulphonate ion incorporation on the physical and blood-contacting properties of a polyetherurethane. Okkema, AZ., Cooper, SL.[2019]

The study identified a new prion protein species, PrP*20, which is detectable in uninfected human and animal brains and may indicate early stages of human prion diseases.

As prion diseases progress, there is a transition from increased levels of PrP*20 to the accumulation of the more pathogenic PrP27-30, suggesting that monitoring PrP*20 could be important for early diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions. Yuan, J., Dong, Z., Guo, JP., et al.[2020]

The polymorphism at codon 129 of the human prion gene (PRNP) significantly affects the conformation and aggregation rates of the prion protein, with the methionine variant (rPrP(C(129M))) showing a more exposed helix 1 region compared to the valine variant (rPrP(C(129V))).

rPrP(C(129M)) aggregates faster and forms more aggregates than rPrP(C(129V)), suggesting that the methionine variant may contribute to a higher risk of prion disease due to its enhanced aggregation properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Normal cellular prion protein with a methionine at position 129 has a more exposed helix 1 and is more prone to aggregate. Pham, N., Yin, S., Yu, S., et al.[2021]

Creutzfeldt-Jakob disease (CJD) and related disorders are now classified as prion diseases, caused by the abnormal conversion of the normal prion protein (PrP) into a disease-causing form (PrP(Sc)), which leads to neurodegeneration.

The review highlights the infectious nature of prions and discusses the emergence of a new variant of CJD linked to a virulent form of bovine spongiform encephalopathy, emphasizing the need for understanding the molecular mechanisms behind these diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fundamentals of prion biology and diseases. DeArmond, SJ., Bouzamondo, E.[2019]

The study found that prions associated with Gerstmann-Sträussler-Scheinker disease (GSS-A117V) are highly infectious, with a significant infectivity level of 109.3 ID50 U/g, despite having a small protease-resistant core that lacks the C-terminus, suggesting that this part of the protein is not necessary for infectivity.

Purified 7 kDa PrPres aggregates, which are non-fibrillar and small, were shown to be highly infectious and capable of encoding the strain characteristics of the original prion sample, supporting the idea that non-fibrillar prion particles are effective in propagating neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of infectious, non-fibrillar and oligomeric prions from a genetic prion disease. Vanni, I., Pirisinu, L., Acevedo-Morantes, C., et al.[2023]

Prion diseases, caused by infectious agents known as prions, include serious conditions like Creutzfeldt-Jakob disease and 'mad cow' disease, and while significant research progress has been made in understanding their pathogenesis, effective diagnostic methods and treatments remain inadequate.

Despite advancements in prion disease research, current diagnostic procedures lack sensitivity, and no therapies have been proven to reliably alter the progression of these neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress and problems in the biology, diagnostics, and therapeutics of prion diseases. Aguzzi, A., Heikenwalder, M., Miele, G.[2019]

References

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

Ixekizumab treatment of biologic-naïve patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1). [2021]

2. England pubmed.ncbi.nlm.nih.gov

Impact of PCSK9 monoclonal antibodies on circulating hs-CRP levels: a systematic review and meta-analysis of randomised controlled trials. [2019]

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

Effect of alirocumab dose increase on LDL lowering and lipid goal attainment in patients with dyslipidemia. [2019]

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

The New Face of Hyperlipidemia and the Role of PCSK9 Inhibitors. [2021]

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

A Phase I Randomized Study of a Specifically Engineered, pH-Sensitive PCSK9 Inhibitor RN317 (PF-05335810) in Hypercholesterolemic Subjects on Statin Therapy. [2021]

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

Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety. [2023]

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

Comparison of DLin-MC3-DMA and ALC-0315 for siRNA Delivery to Hepatocytes and Hepatic Stellate Cells. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Rational design and combinatorial chemistry of ionizable lipids for RNA delivery. [2023]

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

Influence of the Composition of Plasticizer-Free Silicone-Based Ion-Selective Membranes on Signal Stability in Aqueous and Blood Plasma Samples. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of carboxylate and/or sulphonate ion incorporation on the physical and blood-contacting properties of a polyetherurethane. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions. [2020]

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

Normal cellular prion protein with a methionine at position 129 has a more exposed helix 1 and is more prone to aggregate. [2021]

13. Ireland pubmed.ncbi.nlm.nih.gov

Fundamentals of prion biology and diseases. [2019]

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

Isolation of infectious, non-fibrillar and oligomeric prions from a genetic prion disease. [2023]

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

Progress and problems in the biology, diagnostics, and therapeutics of prion diseases. [2019]