The first pediatric patient was treated in the United States, but the company has now also received clearance to treat pediatric patients in the UK.
The first pediatric patient has been dosed in the phase 1/2 REVEAL Pediatric Study clinical trial (NCT06152237) evaluating Taysha Gene Therapies’ TSHA-102, an investigational adeno-associated virus (AAV) vector-based gene therapy, for the treatment of Rett syndrome.1
The first patient in the trial, which is initially treating female patients aged 5 to 8 years who have stage 3 Rett syndrome, was treated in the United States at RUSH University Medical Center in Chicago. Taysha noted alongside this announcement that it has received clearance of a clinical trial application (CTA) from the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA), with which the company plans to expand the trial to the UK.
"Designed as a 1-time, disease-modifying treatment with the ability to mediate MECP2 expression on a cell-by-cell basis, TSHA-102 holds the potential to address a significant unmet medical need for the Rett syndrome community,” Elizabeth Berry-Kravis, MD, PhD, a professor of pediatrics, neurology, and anatomy/Cell biology at RUSH University Medical Center and the principal investigator at that site, said in a statement.1 “By intervening early in disease, we believe TSHA-102 may provide significant therapeutic impact for pediatric patients. I look forward to evaluating this promising gene therapy and its impact on the lives of patients and their caregivers in the clinic.”
The open-label, randomized, trial, which has a dose-escalation and dose-expansion design, will first seek to determine the maximum administered dose (MAD) and maximum tolerated dose (MTD) in patients aged 5 to 8 years at 2 different dose levels. Each dose level will include at least 3 patients in this portion, which is referred to as Part A. Taysha anticipates that dosing of patients in the lowest dose cohort in Part A will be finished in the middle of 2024; the company also plans to announce initial safety and efficacy data at that time. Part B of the study will treat patients in 2 separate aged-based cohorts at either the MAD or MTD. The 2 cohorts will include patients aged 5 to 8 years and patients aged 3 to 5 years, respectively. TSHA-102 is delivered via a single lumbar intrathecal injection.
A separate phase 1/2 clinical trial, referred to simply as REVEAL (NCT05606614), is evaluating TSHA-102 in older patients with Rett syndrome in Canada. Originally open to adult patients only, the trial’s eligibility criteria were expanded in November 2023 to include patients as young as 12 years old.2 As of late 2023, 2 adult patients have been dosed in this trial, and dosing of a third patient is expected by the end of the first quarter of 2024.2,3
The second patient was dosed per a recommendation to proceed made by the trial’s Independent Data Monitoring Committee (IDMC) in July 2023, given following a review of data from the first patient dosed.4,5 In June 2023, Taysha noted that the first patient had been discharged from the hospital in accordance with study protocol and had completed several follow-up visits, with the IDMC’s recommendation based on a prespecified examination of clinical results carried out after the first patient had reached the end of a 42-day posttreatment evaluation period.
“Dosing the first pediatric patient with Rett syndrome marks an important step forward in our efforts to broaden the clinical evaluation of TSHA-102 to younger patients with earlier stages of Rett syndrome,” Sukumar Nagendran, MD, the president and head of research and development at Taysha, added to the statement.1 “We are pleased with our progress on expanding the study of TSHA-102 across a broad population of ages and stages of Rett syndrome to bring a potentially transformative treatment option to all patients and families suffering from this devastating disease. The pediatric trial will build on our ongoing REVEAL adolescent and adult trial, where early data demonstrated improvements across multiple clinical domains in adult patients with the most advanced stage of disease. We also plan to expand our US pediatric trial into the UK following the recent acceptance of our CTA by the MHRA.”