Orbit Study: A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered ION356 in Participants With Pelizaeus Merzbacher Disease (PMD)

Pelizaeus-Merzbacher Disease Clinical Trial

Official title:

A Phase 1b Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION356 in Patients With Pelizaeus Merzbacher Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06150716
• Other study ID #: ION356-CS1
• Secondary ID: 2022-502432-39
• Status: Recruiting
• Phase: Phase 1
• Start date: April 10, 2024
• Est. completion date: June 2028

Study information

• Verified date: June 2024
• Source: Ionis Pharmaceuticals, Inc.
• Contact: Ionis Pharmaceuticals, Inc.
• Phone: (844) 387-9520
• Email: IonisPelizaeusMerzbacherStudy2[@]clinicaltrialmedia.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to evaluate the safety and tolerability of ION356.

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 an open-label long-term extension (LTE) part of 109 weeks. Eligible participants during the MAD portion of the study will receive doses of ION356 and upon completion will seamlessly transition to the open-label LTE to receive doses of ION356.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 2028
• Est. primary completion date: June 2028
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 2 Years to 17 Years

Eligibility

Key Inclusion Criteria

1. 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.

2. Diagnosis of PMD with genetic confirmation of PLP1 gene duplication.

3. Clinical phenotype and brain imaging consistent with a diagnosis of PMD.

4. Male between the ages of 2 and 17 years, inclusive, at the time of informed consent.

5. Able and willing to meet all study requirements (in the opinion of the Investigator), including travel to Study Center, procedures, measurements, and visits.

Exclusion Criteria

1. Clinically significant abnormalities in medical history, laboratory tests or physical examination.

2. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.

3. Any contraindication or unwillingness to undergo magnetic resonance imaging (MRI).

4. 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.

5. 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).

6. History of gene therapy or cell transplantation, or any experimental brain surgery.

7. Current obstructive hydrocephalus.

8. Known brain or spinal disease or previous spinal surgery that would interfere with the lumbar puncture (LP) process, CSF circulation, or safety assessment.

9. Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks prior to Screening or planned during the study.

10. 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.

Related Conditions & MeSH terms

• Pelizaeus-Merzbacher Disease

Intervention

Drug:
• ION356
Administered as intrathecal (IT) injection.

Locations

Country	Name	City	State
France	Ionis Investigative Site	Le Kremlin-Bicêtre
Germany	Ionis Investigative Site	Göttingen
Netherlands	Ionis Investigative Site	Amsterdam
United States	Ionis Investigative Site	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs		Up to Week 145
Primary	Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments		Baseline up to Week 145
Primary	Number of Participants With Clinically Significant Change From Baseline in Neurological Examination Findings		Baseline up to Week 145
Primary	Number of Participants With Clinically Significant Change From Baseline in Vital Signs		Baseline up to Week 145
Primary	Number of Participants With Clinically Significant Change From Baseline in Electrocardiography (ECG)		Baseline up to Week 145
Primary	Number of Participants With Change From Baseline in Concomitant Medication Use		Baseline up to Week 145
Secondary	Maximum Plasma Concentration (Cmax) of ION356		Pre-dose and at multiple points post-dose up to Week 145
Secondary	Area Under the Concentration-time Curve (AUC) of ION356		Pre-dose and at multiple points post-dose up to Week 145
Secondary	Plasma Terminal Elimination Half-life (t½) of ION356		Pre-dose and at multiple points post-dose up to Week 145
Secondary	Plasma Concentration of ION356		Pre-dose and at multiple points post-dose up to Week 145
Secondary	Cerebrospinal Fluid (CSF) Concentration of ION356		Pre-dose and at multiple points post-dose up to Week 105
Secondary	Concentration of ION356 Excreted in Urine		Pre-dose and at multiple points post-dose on Week 1 and Week 49
Secondary	Percent of ION356 Dose Excreted in Urine		Pre-dose and at multiple points post-dose on Week 1 and Week 49
Secondary	Renal Clearance of ION356		Pre-dose and at multiple points post-dose on Week 1 and Week 49