A Study of SmartFlow® Magnetic Resonance (MR) Compatible Ventricular Cannula for Administering Eladocagene Exuparvovec to Pediatric Participants

• ClinicalTrials.gov Identifier: NCT04903288
• Recruitment Status: Recruiting
• First Posted: May 26, 2021
• Last Update Posted: December 21, 2022
• Sponsor: PTC Therapeutics
• Information provided by (Responsible Party): PTC Therapeutics

Tracking Information

• First Submitted Date: May 21, 2021
• First Posted Date: May 26, 2021
• Last Update Posted Date: December 21, 2022
• Actual Study Start Date: May 12, 2021
• Estimated Primary Completion Date: July 15, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 19, 2022): Number of Participants With Adverse Events (AEs) Associated With the Surgical Administration of Eladocagene Exuparvovec Using the SmartFlow® MR-Compatible Ventricular Cannula [ Time Frame: Baseline (Day 1) up to Week 8 ]
• Original Primary Outcome Measures (submitted: May 21, 2021): Number of Participants With Adverse Events (AEs) Associated With the Surgical Administration of Eladocagene Exuparvovec Using the SmartFlow® MR Compatible Ventricular Cannula [ Time Frame: Baseline (Day 1) up to Week 8 ]
• Current Secondary Outcome Measures (submitted: May 21, 2021): Change From Baseline in Positron Emission Tomography (PET) Imaging of Putaminal-Specific L-6-[18F] Fluoro-3,4-Dihydroxyphenylalnine (18F-DOPA) PET Uptake at the End of the Trial Phase (Week 8) [ Time Frame: Baseline (Day 1), Week 8 ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of SmartFlow® Magnetic Resonance (MR) Compatible Ventricular Cannula for Administering Eladocagene Exuparvovec to Pediatric Participants
• Official Title: An Open-Label Trial to Address the Safety of the SmartFlow MR-Compatible Ventricular Cannula for Administering Eladocagene Exuparvovec to Pediatric Subjects
• Brief Summary: This study will have a trial phase, extension phase, and optional long-term extension phase. The primary objective of the trial phase is to assess the safety of the SmartFlow® MR Compatible Ventricular Cannula for administering eladocagene exuparvovec to pediatric participants with aromatic L-amino acid decarboxylase (AADC) deficiency. The extension phase is designed to capture additional clinical information for eladocagene exuparvovec, including changes in motor development, AADC-specific symptoms, and other pharmacodynamic (PD) measures. The optional long-term extension phase is designed to capture long-term safety and efficacy data from participants treated in the trial phase and the extension phase.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: AADC Deficiency

Intervention

Genetic: Eladocagene Exuparvovec

Four 0.08 milliliters (mL) infusions at a dose of 0.45×10^11 vg and a volume of 80 microliters (μl) per site to 4 sites (2 per putamen), for the total dose of 1.8×10^11 vg and a total volume of 320 μl per participant.

Study Arms

Experimental: Eladocagene Exuparvovec

Participants will receive eladocagene exuparvovec intraoperatively at 1.8×10^11 vector genomes (vg) via SmartFlow® MR Compatible Ventricular Cannula in a single operative session. Participants will receive standard of care for their AADC deficiency during the study.

Intervention: Genetic: Eladocagene Exuparvovec

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 21, 2021): 3
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 15, 2023
• Estimated Primary Completion Date: July 15, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Pediatric participants must have genetically-confirmed AADC deficiency with typical clinical characteristics and decreased AADC enzyme activity in plasma.
• Cranium sufficiently developed to allow placement of ClearPoint® system for stereotactic surgery.
• Persistent neurological defects secondary to AADC deficiency despite standard medical therapy (dopamine agonists, monoamine oxidase inhibitor, pyridoxine, or other forms of vitamin B6) in the opinion of the investigator.
• Unable to ambulate independently (with or without assistive device).
• Baseline hematology, chemistry, and coagulation values within the normal pediatric laboratory value ranges, unless in the investigator's opinion the out of range values are not clinically significant with respect to the participant's suitability for surgery.
• Participant must test negative for coronavirus disease of 2019 (COVID-19) a maximum of 72 hours prior to receiving gene therapy.
• Participant must be on stable dosage for 3 months prior to baseline for all medications related to treatment of AADC deficiency, including dopamine agonists, monoamine oxidase inhibitors, anticholinergic drugs, and vitamin B6.
• Females of childbearing potential must have a negative pregnancy test at screening and baseline and agree to abstinence or double-barrier form of contraception for the duration of the study following discharge from the hospital (acceptable methods will be determined by the site).
• Males sexually active with females of childbearing potential must agree to use a barrier method of birth control during the study following discharge from the hospital.
• Parent(s)/legal guardian(s) of the participant must agree to comply with the requirements of the study, including the need for frequent and prolonged follow up.
• Parent(s)/legal guardian(s) with custody of the participant must give their consent for the participant to enroll in the study.

Exclusion Criteria:

• The participant has presence of other significant medical or neurological conditions that would create an unacceptable operative or anesthetic risk.
• Participants with pyridoxine 5'-phosphate oxidase or tetrahydrobiopterin (BH4) deficiency.
• Contraindication for imaging studies (computed tomography [CT] scan, PET, or magnetic resonance imaging [MRI]), including sedation limitations or metal that would interfere with a brain MRI.
• Anti-adeno-associated virus, serotype 2 (anti-AAV2) antibody titer higher than 1:1200 or >1 optical density value by enzyme-linked immunosorbent assay.
• Participants who have received treatment with other experimental therapies within the last 24 weeks prior to planned gene therapy administration, or any treatment ever with a gene therapy.
• Evidence of a clinically active infection.
• Females who are pregnant or breast feeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Patient Advocacy; 1-866-562-4620; medinfo@ptcbio.com

• Listed Location Countries: Israel, Taiwan, United States

Administrative Information

• NCT Number: NCT04903288
• Other Study ID Numbers: PTC-AADC-GT-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: PTC Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: PTC Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: PTC Therapeutics
• Verification Date: December 2022