ATTUNE: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION440 in Participants With Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome (MDS)
- Conditions
- Methyl CpG Binding Protein 2 (MECP2) Duplication Syndrome
- Interventions
- Procedure: Sham procedure
- Registration Number
- NCT06430385
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The primary purpose of this study is to evaluate the safety and tolerability of ION440.
- Detailed Description
This is a phase 1-2 randomized, double-blind, sham-controlled, multiple-ascending dose (MAD) study to evaluate ION440 in pediatric and adult participants with MECP2 Duplication Syndrome (MDS) and will be conducted in two parts. During Part 1 (MAD) (36 weeks), participants will be randomized in a 3:1 ratio to receive ION440 or sham. Individuals who complete Part 1 may enter Part 2, an open label long-term extension study (LTE), where they will receive ION440 for up to approximately 156 weeks. Multiple dose cohorts (Dose A, Dose B, and Dose C) will be evaluated in the study.
All dosing cohorts will be further subdivided by age. Sub cohort A will include participants 8 years of age and older and sub cohort B will include participants 2 through 7 years of age. Dosing cohorts will be enrolled sequentially with sub cohort A initiating prior to sub cohort B.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 48
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 3: ION440 Dose C ION440 Participants will receive ION440 intrathecally at Dose C during Part 1/MAD, followed by ION440 Dose C during Part 2/LTE. Cohort 2: ION440 Dose B ION440 Participants will receive ION440 intrathecally at Dose B during Part 1/MAD, followed by ION440 Dose B during Part 2/LTE. Sham Procedure Sham procedure During the Part 1/MAD period, a lumbar procedure (LP) will be performed at the same frequency as ION440 administration. Participants will not receive ITB injections during this period. It will be followed by the open-label Part 2/LTE period, where participants will receive ION440 at the same dose as their enrolled cohort (e.g. Dose A, Dose B or Dose C). Cohort 1: ION440 Dose A ION440 Participants will receive ION440 intrathecally at Dose A during Part 1/MAD, followed by ION440 Dose A during Part 2/LTE.
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs Baseline up to approximately 36 weeks Part 1: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings Baseline up to approximately 36 weeks Part 1: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Baseline up to approximately 36 weeks Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Up to approximately 36 weeks Part 1: Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments Baseline up to approximately 36 weeks Part 2: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings Baseline up to approximately 192 weeks Part 2: Number of Participants With TEAEs Up to approximately 192 weeks Part 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs Baseline up to approximately 192 weeks Part 2: Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments Baseline up to approximately 192 weeks Part 2: Number of Participants With Clinically Significant Change From Baseline in ECG Baseline up to approximately 192 weeks
- Secondary Outcome Measures
Name Time Method Part 1: Maximum Observed Concentration (Cmax) of ION440 in Plasma Pre-dose and at multiple points post-dose up to Week 36 Part 1: Trough Concentration (Ctrough) of ION440 in Plasma and CSF Pre-dose and at multiple points post-dose up to Week 36 Part 2: Trough Concentration (Ctrough) of ION440 in Plasma and CSF Up to approximately 192 weeks Part 1: Plasma Concentration of ION440 Pre-dose and at multiple points post-dose up to Week 36 Part 1: Plasma Terminal Elimination Half-life (t½) of ION440 Pre-dose and at multiple points post-dose up to Week 36 Part 1: Area Under the Concentration-time Curve (AUC) of ION440 in Plasma Pre-dose and at multiple points post-dose up to Week 36
Related Research Topics
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Trial Locations
- Locations (5)
Rady Children's Hospital
🇺🇸San Diego, California, United States
Gillette Children's Specialty Healthcare
🇺🇸Saint Paul, Minnesota, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States