ION356 for Pelizaeus-Merzbacher Disease

Recruiting at 6 trial locations

Overseen By Ionis Pharmaceuticals, Inc.

Age: < 18

Sex: Male

Trial Phase: Phase 1

Sponsor: Ionis Pharmaceuticals, Inc.

Must not be taking: Investigational drugs

Disqualifiers: Obstructive hydrocephalus, Brain disease, others

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

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on testing the safety and tolerability of a new treatment called ION356, specifically for Pelizaeus-Merzbacher Disease (PMD), a rare genetic disorder affecting brain development. Participants will receive one of two doses of ION356 to assess how their bodies handle it. Boys aged 2 to 17 years, diagnosed with PMD and with genetic confirmation, might be suitable candidates for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking another investigational drug, you must stop at least 1 month before screening, or longer depending on the drug's characteristics.

Is there any evidence suggesting that ION356 is likely to be safe for humans?

Research shows that ION356, a type of genetic therapy, is undergoing safety testing in people with Pelizaeus-Merzbacher Disease. In earlier studies, researchers injected the treatment into the spine and generally found it to be safe. No major changes in symptoms or MRI results occurred, suggesting the treatment did not cause significant harm. However, ION356 remains under study and has not received approval from any health authorities for treating any disease. More information is needed to fully understand its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Pelizaeus-Merzbacher Disease?

Unlike the standard treatments for Pelizaeus-Merzbacher Disease, which typically focus on symptom management and supportive care, ION356 targets the underlying genetic cause of the disease. Researchers are excited about ION356 because it is administered intrathecally, meaning it's delivered directly into the spinal fluid, which allows it to reach the central nervous system more effectively. This targeted delivery method offers the potential for more direct impact on the disease's progression, making ION356 a promising candidate for altering the course of the disease rather than just managing its symptoms.

What evidence suggests that ION356 might be an effective treatment for Pelizaeus-Merzbacher Disease?

Research shows that ION356 is a genetic treatment known as an antisense oligonucleotide. It targets the cause of Pelizaeus-Merzbacher Disease (PMD), a serious condition resulting from changes in the PLP1 gene. This gene affects myelin, the protective layer around nerves. Although health authorities have not yet approved ION356 for effectiveness, it aims to address the genetic cause of the disease. Early studies are investigating how this treatment might slow or alter the disease's progression. Initial research focuses on safety and understanding how the treatment functions in the body, with the hope of offering a new way to manage PMD in the future. Participants in this trial will receive ION356 at different dosages, with Cohort A receiving Dose A and Cohort B receiving Dose B, to evaluate its safety and potential effectiveness. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for boys aged 2-17 with Pelizaeus-Merzbacher Disease (PMD), confirmed by PLP1 gene duplication. They must be able to travel to the study center and comply with all requirements. Parents or guardians need to consent and participate in reporting symptoms.

Inclusion Criteria

I am a male aged between 2 and 17 years.

You are able and willing to complete all the study tasks and visits, including traveling to the study center.

My brain scans and symptoms match those of Pelizaeus-Merzbacher Disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple-Ascending Dose (MAD)

Participants receive multiple ascending doses of ION356 for safety and pharmacokinetics evaluation

48 weeks

Open-label Long-term Extension (LTE)

Participants continue to receive ION356 in an open-label extension to evaluate long-term safety and tolerability

109 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ION356

Trial Overview The Orbit Study is testing ION356, administered into the spinal fluid, to check its safety and how it affects the body in young males with PMD. The main goal is to see if it's safe and tolerable for these patients.

How Is the Trial Designed?

Group I: Cohort B: ION356 Dose B Experimental Treatment 1 Intervention

Participants will receive ION356 intrathecally at Dose B in the MAD Period, followed by ION356 Dose B in the LTE Period.

Group II: Cohort A: ION356 Dose A Experimental Treatment 1 Intervention

Participants will receive ION356 intrathecally at Dose A in the MAD Period, followed by ION356 Dose A in the LTE 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

Citations

1. neurology.ionis.com neurology.ionis.com/sites/default/files/2024-10/Pelizaeus-Merzbacher%20Disease%20Clinical%20Trial%20Handout.pdf

SY1269229_PMD_CT Handout_rd05_v02_PRINT - IONIS ION356 has not been evaluated for safety and efficacy by any regulatory authorities and is not indicated for the treatment of any disease. 157 weeks. Part 1: 48 ...

2. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-ion356-for-patients-with-pelizaeus-merzbacher-disease/

Study on the Safety and Effects of ION356 for Patients ... This study evaluates the safety and effects of ION356, an antisense oligonucleotide, injected intrathecally for patients with Pelizaeus-Merzbacher Disease, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11081862/

Pelizaeus-Merzbacher Disease: On the Cusp of Myelin Medicine As a major component of myelin, mutated PLP1 causes progressive neurodegeneration and eventually death due to severe white matter deficits. Medical care has ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06150716?term=orbit%20pmd&rank=1

NCT06150716 | Orbit Study: A Study to Evaluate the Safety ... This is a Phase 1b, open-label multiple-ascending dose (MAD) study of ION356 in approximately 24 pediatric participants with Pelizaeus-Merzbacher Disease and ...

5. pmdfoundation.org pmdfoundation.org/blog/ionis-pharmaceuticals-announces-clinical-study

Ionis Pharmaceuticals Announces Clinical Study Ionis Pharmaceuticals has announced the ORBIT Study to evaluate the safety, pharmacokinetics, and pharmacodynamics of intrathecally administered ION356 in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06150716

NCT06150716 | Orbit Study: A Study to Evaluate the Safety ... The primary purpose of this study is to evaluate the safety and tolerability of ION356. Detailed Description. This is a Phase 1b, open-label multiple-ascending ...

7. alextlc.org alextlc.org/news/update-on-ionis-pmd-clinical-trial/

Update on Ionis' PMD Clinical Trial New clinical sites open in US and Germany for Ionis ORBIT Phase 1 clinical trial of an investigational drug, ION356, in people with Pelizaeus-Merzbacher ...