๐ฌIn plain words
What the trial is, and whether it could suit you
This is a registrational, first-in-human, open-label, dose escalation and expansion study evaluating the safety, tolerability and effectiveness of TTX-381, administered by injection under the retina, for the treatment of eye problems caused by CLN2 (Batten disease). The study includes dose escalation and expansion groups evaluating treatment in one or both eyes. Participants are followed for 5 years after treatment to assess safety and clinical outcomes.
Sign in to get the eligibility rules as simple questions to take to your doctor.
๐ Eligibility rules (as published)
Inclusion Criteria:
Participants must meet all of the following criteria:
* Biallelic CLN2 mutations.
* Decreased leukocyte TPP1 activity.
* Clinical signs or symptoms consistent with CLN2 disease, such as developmental delay or decline, seizures, vision loss, or an older sibling with confirmed CLN2 diagnosis.
* Currently receiving biweekly ICV ERT treatment with cerliponase alfa.
* Age โฅ24 month and โค84 months at screening
* In the phase of accelerated decline in CRT with the following baseline retinal criteria confirmed by the central reading center:
1. CRT โค210 ฮผm and
2. CRT โฅ140 ฮผm in both eyes and
* Is willing and able to comply with the protocol and 5-year visit schedule.
Written informed consent must be provided by the participants parent(s) or legally authorized representative(s)
Exclusion Criteria:
Participants will be excluded if any of the following criteria apply:
* Any ocular or systemic condition that, in the investigator's opinion, would prevent administration or evaluation of TTX-381, interfere with interpretation of participant safety or study results or make the participant unsuitable for the study. (eg, significant lens or corneal opacities, glaucoma, amblyopia, gross retinal anatomical abnormality, etc).
* Difference in CRT measurement between the right and left eye \>10ฮผm at screening
* Prior Grade 3 or 4 hypersensitivity reaction, to ICV cerliponase alfa infusion. (eg, bronchospasm and hypotension requiring intravenous treatment, cardiac dysfunction, anaphylaxis)
* Any contraindication that would prevent continued administration of ICV cerliponase alfa, including ventriculo-peritoneal shunt, acute intracerebroventricular access device leakage, device failure, or device-related infection.
* Prior participation in a gene therapy study.
* Prior participation in another ocular clinical trial, except an intravitreal cerliponase alfa trial where a subject has received a maximum of 3 injections and the PI, Medical Monitor, and Sponsor all agree that he/she can safely and successfully participate in the study after a washout period of 3 or more months.
* Prior intraocular injections of any kind, except prior treatment with an maximum of 3 ICV injections of cerliponase alfa if at least 3 months have passed since last injection.
* Participation in a nonocular clinical study with an investigational drug within 6 months prior to screening, except for intracerebroventricular cerliponase alfa.
* Ocular surgery within 6 months prior to screening.
* Prior bone marrow transplant.
* Use of the following medications within the 30 days prior to treatment: gemfibrozil, mycophenolate, prednisone or other steroids for the intended purpose of treating NCL (Steroid treatment for asthma is not excluded),
* Known sensitivity or contraindications to medications planned for use in the peri-operative period.
* Contraindications to systemic immunosuppression.
* Severe renal insufficiency as determined by an estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2, based on creatinine, at Screening
* Severe hepatic insufficiency as determined by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 ร upper limit of normal (ULN) or total bilirubin \> 1.5 ร ULN at Screening Visit 1, unless the subject has a previously known history of Gilbert's syndrome and a fractionated bilirubin that shows conjugated bilirubin \< 35% of total bilirubin.
* Mutations in another CLN gene.
* Mutation in another gene associated with inherited retinal disease.
* Contraindications to intraocular surgery (eg, severe coagulopathy).
* Positive urine pregnancy test at Screening (applying only to females of childbearing potential).
* Any other condition that would not allow the potential participant to complete follow-up examinations during the study or, in the opinion of the investigator, makes the potential participant unsuitable for the study.
* The participant had a positive polymerase chain reaction (PCR) viral test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2 PCR) within the last 4 weeks before signing the informed consent form (ICF) or has persistent coronavirus disease (COVID-19) symptoms regardless of when the last SARS-CoV2 PCR viral test was performed or when the infection occurred.
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