Continuation Study of Latozinemab in Patients with Neurodegenerative Diseases Following Prior Participation in Alector-Sponsored Trials

The primary objective of this study is to provide continued access to **latozinemab** for participants who have previously participated in a latozinemab study sponsored by Alector, or in partnership or collaboration with Alector. This is clinically relevant as it allows for the ongoing evaluation of the long-term effects and potential benefits of latozinemab in individuals with **neurodegenerative diseases**, ensuring that participants can maintain their treatment regimen without interruption.

Secondary objectives include:

• To monitor the safety and tolerability of latozinemab, measured by safety assessments and anti-drug antibodies (ADAs).
• To monitor the clinical benefit of ongoing treatment with latozinemab for participants using clinical outcome assessments (COAs).

The clinical trial involves a total of **20 participants** who have previously participated in a latozinemab study. The study population includes both **male and female subjects**. Participants are adults, with an age range that includes individuals from 18 to 64 years old. The trial population was selected based on their successful completion of a prior latozinemab study, ensuring they have experience with the treatment under investigation. Participants are required to be in a general health status that allows them to comply with the study protocol requirements. Lifestyle considerations such as diet and physical activity are not specified, but participants must agree to use effective contraception and refrain from donating blood or blood products during and after the study. The study includes a vulnerable population, indicating that special considerations are in place to protect these individuals. The primary medical condition under investigation is **neurodegenerative diseases**. Key inclusion criteria include the ability to provide informed consent and adherence to contraceptive guidelines for both men and women. The trial does not specify any exclusion criteria beyond those related to consent and previous study completion.

The clinical trial is designed to evaluate the continued access to **latozinemab** for participants with **neurodegenerative diseases** who have previously participated in a related study. This trial is a Phase 3, randomized, double-blind, controlled study aimed at monitoring the safety and tolerability of the investigational product. The trial is expected to commence recruitment on August 31, 2024, and conclude by July 31, 2027, with a maximum treatment period of 39 weeks for each participant. Participants will receive **latozinemab** via intravenous infusion, with a maximum daily dose of 60 mg/kg and a total dose not exceeding 2340 mg/kg.

The study involves a sequence of visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as successful completion of a previous **latozinemab** study and the ability to provide informed consent. Women of childbearing potential must agree to use effective contraception, and men must agree to use acceptable contraception and refrain from donating sperm during the study and for 10 weeks after the last dose. Follow-up visits will occur at regular intervals to assess the primary endpoints, including the number of participants receiving **latozinemab** and the duration of treatment, as well as secondary endpoints such as the incidence of adverse events and the development of anti-drug antibodies. The end-of-study visit will evaluate the overall safety and efficacy outcomes.

Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including non-compliance with the study protocol or the occurrence of significant adverse events. The study aims to ensure that participants do not donate blood or blood products for transfusion during the study and for one year after the final dose. The trial's design and procedures are structured to maintain scientific rigor and ensure the collection of reliable data on the investigational product's safety and efficacy in the target population.

The clinical trial involves the administration of **latozinemab**, an experimental medication developed by Alector Inc. Latozinemab is formulated as a **solution for infusion** and is administered via **intravenous infusion**. The dosing regimen for latozinemab is based on a weight-adjusted protocol, with a maximum daily dose of 60 mg/kg and a total maximum dose of 2340 mg/kg over the course of the treatment period. The maximum treatment duration is 39 weeks. Latozinemab is classified as an orphan drug, indicating its use in the treatment of rare conditions, specifically neurodegenerative diseases. The active substance in latozinemab is a protein of other origin, which is not classified under a specific ATC code.

In this continuation study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The primary objective is to provide continued access to latozinemab for participants who have previously participated in a related study. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The study does not include a pediatric formulation, and the pharmaceutical form remains consistent as a solution for infusion throughout the trial duration.

Efficacy in the clinical trial of latozinemab for participants with neurodegenerative disease will be assessed using both primary and secondary endpoints. The primary endpoints include the number of participants receiving latozinemab and the duration of treatment. Secondary endpoints focus on safety and include the number, percentages, nature, and severity of adverse events (AEs) and serious adverse events (SAEs), as well as the number and percentage of cases of the development of anti-drug antibodies (ADAs) to latozinemab. Additionally, the trial will measure the actual values of the Clinical Global Impression - Severity (CGI-S) and Clinical Global Impression - Improvement (CGI-I) every three months to evaluate changes in the participants' condition over time.