Clinical Trials

Date: 2019-01-07

Type of information: update on patient enrollment

phase: 2

Announcement: update

Company: Voyager Therapeutics (USA-MA)

Product: VY-AADC

Action mechanism:

• gene therapy. VY-AADC is an adeno-associated viral vector serotype 2 encoding human aromatic L-amino acid decarboxylase (AAV2-hAADC). It is designed to deliver the AADC gene directly into neurons of the putamen where dopamine receptors are located, bypassing the substantia nigra neurons and enabling the neurons of the putamen to express the AADC enzyme to convert levodopa into dopamine.  The approach with VY-AADC, therefore, has the potential to durably enhance the conversion of levodopa to dopamine and provide clinically meaningful improvements by restoring motor function in patients and improving symptoms following a single administration.

Disease: Parkinson's disease

Therapeutic area: Neurological diseases - Neurodegenerative diseases

Country: USA

Trial details:

• The Phase 2 RESTORE-1 trial will enroll patients who have been diagnosed with Parkinson’s disease for at least four years, are not responding adequately to oral medications, and have at least three hours of OFF time during the day as measured by a validated self-reported patient diary. Patients who meet the eligibility criteria will be randomized (1:1) to one-time administration of VY-AADC (for a total dose of up to 2.5×1012 vector genomes) or placebo surgery.
• The primary endpoint of RESTORE-1 is ON time without troublesome dyskinesia, or good ON time, as measured by a self-reported patient diary at 12 months. Secondary endpoints include diary OFF time, other motor function and quality of life measures from the United Parkinson’s Disease Rating Scales (UPDRS-II,-III scores), the Parkinson’s Disease Questionnaire (PDQ-39), and patient’s global function as measured by the proportion of participants with improvement on the Clinical Global Impression (CGI) score. The trial will also measure non-motor symptoms from the Non-Motor Symptom Scale (NMSS), as well as safety.
• Biomarker data include measurements of the coverage of the specific region of the brain (putamen) targeted with VY-AADC and measurements of AADC enzyme expression and activity in the putamen measured by positron emission tomography (PET) using fluorodopa F-18. Changes in patients’ daily doses of oral levodopa and related medications will also be recorded. (NCT03562494)

Latest news:

• • On January 7, 2019, Voyager Therapeutics announced an update to its VY-AADC clinical program for Parkinson’s disease. In December 2018, the company held a Type B meeting with the FDA to discuss the overall development program for VY-AADC. Based on the meeting discussion and subsequent written feedback from the FDA, Voyager plans to submit a revised trial protocol that will include an increase in the target number of patients in the RESTORE-1 Phase 2 trial, resulting in 75 to 100 total patients in the trial, and to conduct a staggered-parallel Phase 3 trial (RESTORE-2) of similar size and design to RESTORE-1. These updates incorporate guidance from the FDA from the Type B meeting to conduct two adequate and well-controlled clinical trials for a large patient population such as Parkinson’s disease. The RESTORE-1 Phase 2 trial is currently enrolling patients who have been diagnosed with Parkinson’s disease for at least four years, are not responding adequately to oral medications, and have at least three hours of OFF time during the day as measured by a validated self-reported patient diary. Patients who meet the eligibility criteria are randomized (1:1) to one-time administration of VY-AADC or placebo surgery. The primary efficacy endpoint of RESTORE-1 is ON time without troublesome dyskinesia, or good ON time, as measured by a validated self-reported patient diary at 12 months. In addition, Voyager will continue to follow patients on a blinded basis beyond 12 months to obtain additional safety data and to assess the durability of the potential beneficial effects. Secondary endpoints include diary OFF time, other motor function and quality of life measures from the United Parkinson’s Disease Rating Scales (UPDRS-II,-III scores), the Parkinson’s Disease Questionnaire (PDQ-39), and patient’s global function as measured by the proportion of participants with improvement on the Clinical Global Impression (CGI) score. The trial will also measure non-motor symptoms from the Non-Motor Symptom Scale (NMSS), as well as safety. Biomarker data include measurements of the coverage of the specific region of the brain (putamen) targeted with VY-AADC and measurements of AADC enzyme expression and activity in the putamen measured by positron emission tomography (PET) using fluorodopa F-18. Changes in patients’ daily doses of oral levodopa and related medications will also be recorded. Voyager expects RESTORE-1 will take approximately 15 to 21 months to enroll. Voyager plans to begin enrolling patients in RESTORE-2 in both active Phase 2 sites and additional sites globally in the first half of 2020. Voyager anticipates that, if positive, results from RESTORE-1 and RESTORE-2 could potentially form the basis for submission of a biologics license application (BLA) to the FDA for VY-AADC for the treatment of Parkinson’s disease. • On December 10, 2018, Voyager Therapeutics announced dosing of the first patient in RESTORE-1, a Phase 2, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of VY-AADC for the treatment of Parkinson’s disease in patients with motor fluctuations that are refractory to medical management.

 

Is general: Yes