Patient Eligibility Expanded for Phase 1/2 REVEAL Trial of TSHA-102 in Rett Syndrome


Health Canada has greenlit a protocol amendment for Taysha Gene Therapies’ trial to include patients aged 12 years and older, rather than only adult patients.

Sukumar Nagendran, MD, the president and head of R&D at Taysha

Sukumar Nagendran, MD

Health Canada has granted authorization of a protocol amendment to the ongoing phase 1/2 REVEAL trial (NCT05606614) of Taysha Gene Therapies’ investigational treatment TSHA-102, according to a recent announcement.1

The trial was originally planned to assess the gene therapy in a population of 18 adult patients with Rett syndrome, with this adjustment expanding eligibility to include patients aged 12 years and older. Taysha noted that it anticipates dosing the first pediatric patient in REVEAL in the first quarter of 2024. Dosing of the third adult patient, and the completion of dosing in the low-dose cohort 1, is planned for either the fourth quarter of 2023 or the first quarter of 2024.

“Following review of the initial clinical data from the first 2 adult patients treated with TSHA-102 and Chemistry, Manufacturing, and Controls (CMC) data, Health Canada has authorized our protocol amendment to include adolescent patients aged 12 years and older in the ongoing REVEAL Phase 1/2 adult trial. Amending our protocol broadens the patient population who can potentially benefit from TSHA-102. We look forward to further advancing the clinical development of TSHA-102 and building on the encouraging data demonstrated in the first two adult patients treated,” Sukumar Nagendran, MD, the president and head of R&D at Taysha, said in a statement.1

Health Canada cleared the REVEAL trial in March 2022,2 and now the FDA has given the go-ahead for Taysha’s investigational new drug (IND) application for TSHA-102 in pediatric patients with Rett syndrome, after previously granting the treatment fast track designation in August 2023.3

READ MORE: Taysha Doses Second Patient With Rett Syndrome With TSHA-102, per IDMC Recommendation

“Health Canada’s clearance of the protocol amendment is an important milestone in our quest to develop a potentially transformative treatment for all patients and families in the Rett syndrome community,” Rumana Haque-Ahmed, the senior vice president of Regulatory Affairs at Taysha, said in a statement.1 “We look forward to future discussions with Health Canada and other regulatory authorities as we execute on our development plan to bring TSHA-102 to patients as safely and expeditiously as possible.”

REVEAL is a first-in-human, open-label, randomized, dose-escalation and dose-expansion study evaluating the safety and preliminary efficacy of TSHA-102 in women and girls with stage 4 Rett syndrome because of a MECP2 loss-of-function mutation. The gene therapy is administered as a single intrathecal lumbar injection, and the trial’s dose escalation will evaluate 2 levels sequentially, with an aim of identifying the maximum tolerated dose and maximum administered dose, which will then be given during the dose expansion phase of the trial.

Key Takeaways

  1. Health Canada approved a protocol change for Taysha Gene Therapies’ REVEAL trial of TSHA-102, expanding eligibility to patients aged 12 and older.
  2. Taysha expects to dose the first pediatric patient in the phase 1/2 REVEAL trial (NCT05606614) in Q1 2024.
  3. The FDA also greenlit Taysha’s IND application for TSHA-102 in pediatric patients with Rett syndrome.

Taysha announced that it had dosed the second patient in the trial in October 2023, per a recommendation to proceed made by the trial’s Independent Data Monitoring Committee (IDMC) in July 2023.4,5 That recommendation was given following a review of data from the first patient dosed. 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,5 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.

All of this news follows the September announcement that Taysha was discontinuing the development of its lead candidate, TSHA-120, another investigational adeno-associated virus (AAV) vector-based gene therapy that was being evaluated for the treatment of giant axonal neuropathy (GAN).6 The company made the decision after feedback from a Type C meeting with the FDA related to a roadmap to approval for the therapy. Taysha also announced at the time that Astellas Gene Therapies, with which Taysha has an option agreement, had made the choice not to claim an exclusive license for TSHA-120.

1. Taysha Gene Therapies Announces Expanded Eligibility in REVEAL Phase 1/2 Adult Trial to Include Adolescent Rett Syndrome Patients. News release. Taysha Gene Therapies. November 29, 2023. Accessed December 1, 2023.
2. Taysha Gene Therapies provides update on TSHA-120 program in giant axonal neuropathy and a 2023 corporate outlook. News release. Taysha Gene Therapies, Inc. January 31, 2023. Accessed December 1, 2023.
3. Taysha Gene Therapies Announces Fast Track Designation Granted by U.S. FDA for TSHA-102 in Rett Syndrome. News Release. Taysha Gene Therapies. Published August 24, 2023. Accessed December 1, 2023.
4. Taysha Gene Therapies announces positive recommendation from independent data monitoring committee of REVEAL phase 1/2 trial in Rett syndrome. News release. Taysha Gene Therapies, Inc. July 31, 2023. Accessed December 1, 2023.
5. Taysha Gene Therapies provides clinical updates for investigational programs TSHA-120 in giant axonal neuropathy (GAN) and TSHA-102 in Rett syndrome at R&D day. News release. Taysha Gene Therapies, Inc. June 28, 2023. Accessed December 1, 2023.
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