Pelizaeus-Merzbacher DiseasePhase 1NCT06150716
Orbit Study: A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered ION356 in Participants With Pelizaeus Merzbacher Disease (PMD)
A Phase 1 study testing ION356 in people with Pelizaeus-Merzbacher Disease, run by Ionis Pharmaceuticals, Inc. at 7 sites in 5 countries.
Trial summary
The primary purpose of this study is to evaluate the safety and tolerability of ION356. Read more about this study
- Who is it for?
- Ages 2 to 17 years, men only
- Conditions the study is for
- Pelizaeus-Merzbacher Disease
- What is being tested?
- ION356
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 7 sitesin 5 countries
- Study dates
- 10 Apr 2024to Jun 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 17 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Participant's parent or legally accepted representative can provide informed consent, attend all scheduled study visits, provide feedback regarding the participant's symptoms, and can comply with all study requirements.
- Diagnosis of PMD with genetic confirmation of PLP1 gene duplication.
- Clinical phenotype and brain imaging consistent with a diagnosis of PMD.
- Male between the ages of 2 and 17 years, inclusive, at the time of informed consent.
- Able and willing to meet all study requirements (in the opinion of the Investigator), including travel to Study Center, procedures, measurements, and visits.
Who cannot join
- Clinically significant abnormalities in medical history, laboratory tests or physical examination.
- Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
- Any contraindication or unwillingness to undergo magnetic resonance imaging (MRI).
- Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of the investigational agent, whichever is longer.
- Previous treatment with an oligonucleotide (including small interfering ribonucleic acid) within 4 months of Screening if a single dose was received, or within 12 months of Screening if multiple doses were received. This exclusion does not apply to vaccines (both messenger ribonucleic acid [mRNA] and viral vector vaccines).
- History of gene therapy or cell transplantation, or any experimental brain surgery.
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- Current obstructive hydrocephalus.
- Known brain or spinal disease or previous spinal surgery that would interfere with the lumbar puncture (LP) process, CSF circulation, or safety assessment.
- Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks prior to Screening or planned during the study.
- Have any other conditions, which, in the opinion of the Investigator, would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the study.
Trial locations and contacts
7 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
Ionis Pharmaceuticals, Inc. contact
7 sites in 5 countries
United States3 sites, 3 recruiting
- Recruiting
Ionis Investigative Site
Atlanta, Georgia, 30342
- Recruiting
Ionis Investigative Site
Philadelphia, Pennsylvania, 19104
- Recruiting
Ionis Investigative Site
Salt Lake City, Utah, 84113
France1 site, 1 recruiting
- Recruiting
Ionis Investigative Site
Le Kremlin-Bicêtre, 94270
Germany1 site, 1 recruiting
- Recruiting
Ionis Investigative Site
Göttingen, 37075
Netherlands1 site, 1 recruiting
- Recruiting
Ionis Investigative Site
Amsterdam, 1105AZ
About this study
Official title: A Phase 1b Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION356 in Patients With Pelizaeus Merzbacher Disease
The primary purpose of this study is to evaluate the safety and tolerability of ION356.
Read the detailed description
This is a Phase 1b, open-label multiple-ascending dose (MAD) study of ION356 in approximately 24 pediatric participants with Pelizaeus-Merzbacher Disease and genetic confirmation of proteolipid protein 1 (PLP1) gene duplication. The study will have 2 parts: a 48-week multiple-ascending dose (MAD) part followed by a long-term extension (LTE) part of 109 weeks. Eligible participants will receive doses of ION356 during the MAD portion of the study and upon completion will seamlessly transition to the open-label LTE to receive doses of ION356.
- Conditions
- Pelizaeus-Merzbacher Disease
- Being tested
- ION356
- Medical subject headings
- Pelizaeus-Merzbacher Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ION356Drug
Administered as intrathecal (IT) injection.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: ION356 Dose A | Experimental | Participants will receive ION356 intrathecally at Dose A in the MAD Period, followed by ION356 Dose A in the LTE Period. Receives: Drug: ION356 |
| Cohort B: ION356 Dose B | Experimental | Participants will receive ION356 intrathecally at Dose B in the MAD Period, followed by ION356 Dose B in the LTE Period. Receives: Drug: ION356 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Measured: Up to Week 145
Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments
Measured: Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Neurological Examination Findings
Measured: Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Measured: Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Electrocardiography (ECG)
Measured: Baseline up to Week 145
Number of Participants With Change From Baseline in Concomitant Medication Use
Measured: Baseline up to Week 145
Secondary outcomes (8)
Maximum Plasma Concentration (Cmax) of ION356
Measured: Pre-dose and at multiple points post-dose up to Week 145
Area Under the Concentration-time Curve (AUC) of ION356
Measured: Pre-dose and at multiple points post-dose up to Week 145
Plasma Terminal Elimination Half-life (t½) of ION356
Measured: Pre-dose and at multiple points post-dose up to Week 145
Plasma Concentration of ION356
Measured: Pre-dose and at multiple points post-dose up to Week 145
Cerebrospinal Fluid (CSF) Concentration of ION356
Measured: Pre-dose and at multiple points post-dose up to Week 105
Concentration of ION356 Excreted in Urine
Measured: Pre-dose and at multiple points post-dose on Week 1 and Week 49
Percent of ION356 Dose Excreted in Urine
Measured: Pre-dose and at multiple points post-dose on Week 1 and Week 49
Renal Clearance of ION356
Measured: Pre-dose and at multiple points post-dose on Week 1 and Week 49
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2023
- Study start10 Apr 2024
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pelizaeus-Merzbacher DiseaseStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06150716
- Sponsor's protocol ID
- ION356-CS1
- Other IDs
- 2022-502432-39
- Status last verified
- Dec 2025
- First submitted
- 21 Nov 2023
- Last updated
- 12 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION356 in Patients With Pelizaeus Merzbacher Disease
- ClinicalTrials.gov ID
- NCT06150716
- Acronym / sponsor ID
- ION356-CS1
- Conditions
- Pelizaeus-Merzbacher Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Apr 2024 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 29 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 dose (MAD) study of ION356 in approximately 24 pediatric participants with Pelizaeus-Merzbacher Disease and genetic confirmation of proteolipid protein 1 (PLP1) gene duplication. The study will have 2 parts: a 48-week multiple-ascending dose (MAD) part followed by a long-term extension (LTE) part of 109 weeks. Eligible participants will receive doses of ION356 during the MAD portion of the study and upon completion will seamlessly transition to the open-label LTE to receive doses of ION356.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A: ION356 Dose A | Experimental | Drug: ION356Participants will receive ION356 intrathecally at Dose A in the MAD Period, followed by ION356 Dose A in the LTE Period. |
| Cohort B: ION356 Dose B | Experimental | Drug: ION356Participants will receive ION356 intrathecally at Dose B in the MAD Period, followed by ION356 Dose B in the LTE Period. |
Who may qualify
- Ages
- 2 to 17 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Participant's parent or legally accepted representative can provide informed consent, attend all scheduled study visits, provide feedback regarding the participant's symptoms, and can comply with all study requirements.
- Diagnosis of PMD with genetic confirmation of PLP1 gene duplication.
- Clinical phenotype and brain imaging consistent with a diagnosis of PMD.
- Male between the ages of 2 and 17 years, inclusive, at the time of informed consent.
- Able and willing to meet all study requirements (in the opinion of the Investigator), including travel to Study Center, procedures, measurements, and visits.
Key exclusion criteria (10 listed)
- Clinically significant abnormalities in medical history, laboratory tests or physical examination.
- Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
- Any contraindication or unwillingness to undergo magnetic resonance imaging (MRI).
- Treatment with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of the investigational agent, whichever is longer.
- Previous treatment with an oligonucleotide (including small interfering ribonucleic acid) within 4 months of Screening if a single dose was received, or within 12 months of Screening if multiple doses were received. This exclusion does not apply to vaccines (both messenger ribonucleic acid [mRNA] and viral vector vaccines).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ION356Administered as intrathecal (IT) injection. | Drug | Cohort A: ION356 Dose A, Cohort B: ION356 Dose B |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Up to Week 145
Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments
Time frame: Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Neurological Examination Findings
Time frame: Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Electrocardiography (ECG)
Time frame: Baseline up to Week 145
Number of Participants With Change From Baseline in Concomitant Medication Use
Time frame: Baseline up to Week 145
8 secondary outcomes
Maximum Plasma Concentration (Cmax) of ION356
Time frame: Pre-dose and at multiple points post-dose up to Week 145
Area Under the Concentration-time Curve (AUC) of ION356
Time frame: Pre-dose and at multiple points post-dose up to Week 145
Plasma Terminal Elimination Half-life (t½) of ION356
Time frame: Pre-dose and at multiple points post-dose up to Week 145
Plasma Concentration of ION356
Time frame: Pre-dose and at multiple points post-dose up to Week 145
Cerebrospinal Fluid (CSF) Concentration of ION356
Time frame: Pre-dose and at multiple points post-dose up to Week 105
Concentration of ION356 Excreted in Urine
Time frame: Pre-dose and at multiple points post-dose on Week 1 and Week 49
Percent of ION356 Dose Excreted in Urine
Time frame: Pre-dose and at multiple points post-dose on Week 1 and Week 49
Renal Clearance of ION356
Time frame: Pre-dose and at multiple points post-dose on Week 1 and Week 49
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2025.
- Individual participant dataSharing planned: Yes. Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ionis Pharmaceuticals, Inc. contact
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ION356 in people with Pelizaeus-Merzbacher Disease, run by Ionis Pharmaceuticals, Inc. at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, France, Germany, Japan, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ionis Pharmaceuticals, Inc. ((844) 387-9520, IonisPelizaeusMerzbacherStudy2@clinicaltrialmedia.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs (time frame: Up to Week 145). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2025.