A Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of AL001 in FTD

Phase 1

Conditions: Frontotemporal Dementia
MedDRA version: 21.1Level: PTClassification code 10068968Term: Frontotemporal dementiaSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2019-004066-18-FR

Lead Sponsor: Alector Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 180

Inclusion Criteria

Each participant must meet all of the following criteria to be enrolled in this study.
Key Inclusion Criteria:
•Participant is a known carrier of a heterozygous loss-of-function GRN mutation causative of FTD, with either:
•A global CDR® plus NACC FTLD score of 0 and an elevated level of serum NfL as measured on the Simoa NF-Light Advantage Kit assay (pre-symptomatic participants) or,
• A global CDR® plus NACC FTLD score of 0.5, 1, or 2; and 1 or more of the
6 behavioral/cognitive symptoms required for a diagnosis of possible bvFTD, or a diagnosis of PPA (symptomatic participants).

General Inclusion Criteria:
2. Presymptomatic participants (with a global CDR® plus NACC FTLD score of 0) are 45 to 85 years of age, inclusive, at screening, or symptomatic participants (with a global CDR® plus NACC FTLD score of 0.5,1, or 2) are 25 to 85 years of age, inclusive, at screening
3. At screening, female participants must be nonpregnant and nonlactating, and 1 of the following conditions must apply:
a. Participant is not a woman of childbearing potential (WOCBP) (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1-year postmenopausal [amenorrhea duration of 12 consecutive months with no identified cause other than menopause]).
b. Participant is a WOCBP and agrees to use an acceptable contraceptive method from screening until 10 weeks after the last dose of study treatment. Acceptable contraception is defined as using hormonal contraceptives (e.g. combined oral contraceptive pill) or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom. In addition, total abstinence, in accordance with the lifestyle of the participant, is acceptable.
A WOCBP must have a serum pregnancy test conducted at screening. Additional requirements for pregnancy testing during and after study intervention are described in the Schedules of Assessments.
4. Male participants must agree to use acceptable contraception and not donate sperm from Day 0 until 10 weeks after the last dose of study treatment. Acceptable contraception for the male participant when having sexual intercourse with a WOCBP who is not currently pregnant is defined as using a condom. In addition, WOCBP partners must use hormonal contraceptives (e.g. combined oral contraceptive pill) or an intrauterine device.
5. Participant agrees not to donate blood or blood products for transfusion for the duration of the study and for 1 year after the final dose of study treatment.
6. Participant is willing to and can comply with the study protocol requirements, in the opinion of the investigator.
7. Participant is willing and able to give informed consent. If the study participant is not competent, a legally authorized representative must provide informed consent on their behalf, and the participant must provide assent, in accordance with the local regulations, guidelines, and institutional review board (IRB) or independent ethics committee (IEC).
8. Participant has availability of a person (study partner”) who has frequent and sufficient contact with the participant (at least 5 hours per week of in-person contact), can provide accurate information regarding the participant’s behavior, cognitive, and functional abilities as well as their health throughout the study, agrees to provide information at investigational site visits that require partner input for COA completion, and gives t

Exclusion Criteria

1. Participant has dementia due to a condition other than FTD including, but not limited to, Alzheimer’s disease, Parkinson’s disease, dementia with Lewy bodies, Huntington disease, or vascular dementia.
2. Participant has a known mutation causative of neurodegenerative disorder(s) other than heterozygous loss-of-function GRN mutations causative of FTD.
3. Participant has a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
4. Participant has a history of moderate or severe substance use disorder within the past
2 years, with the exception of nicotine, as defined by the Diagnostic and Statistical
Manual of Mental Disorders, fifth edition criteria
5. Participant currently has or has had an acute illness that requires or required systemic antibiotics within 30 days prior to study treatment administration.
6. Participant has clinically significant vitamin B12 or folate deficiency (if treated, must be on a stable regimen for at least 3 months prior to study treatment administration).
7. Participant has untreated hypothyroidism (if treated, thyroid supplementation dose must be stable for at least 3 months with a normal thyroid-stimulating hormone level prior to study treatment administration).
8. Participant has insufficiently controlled diabetes mellitus (e.g., hemoglobin A1C
=8%).
9. Participant has had any surgery (major or emergent) or hospitalization within 30 days prior to study treatment administration.
10. Participant has a history of cancer except if it:
a.Is considered likely to be cured; b.Is not being actively treated with anticancer therapy or radiation and in the opinion of the investigator, is not likely to require treatment in the ensuing
3 years; c.Is considered to have low probability of recurrence (with supporting documentation from the treating oncologist if possible), including participants with ongoing antihormonal treatment (e.g., tamoxifen);d.For prostate cancer, has not had significant progression within the past 2 years.
11. Participant is positive for hepatitis B surface antigen, human immunodeficiency
virus-1 or -2 antibodies or antigen, or history of spirochetal infection of the CNS (e.g., syphilis, borreliosis, or Lyme disease). Participants with a positive hepatitis C virus antibody will be allowed if hepatitis C RNA is negative.
12. Participant has significant kidney disease as indicated by either of the following:
a. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, according to the re-expressed abbreviated (four-variable) MDRD Study equation
b.Creatinine =2 mg/dL.
13. Participant has impaired hepatic function as indicated by screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =2.5 the upper limit of normal (ULN), or total bilirubin =2.0 × ULN. Note: Participants with Gilbert's syndrome are eligible to participate
14. Participant has hematologic abnormalities as indicated by hemoglobin =9 g/dL; white blood cells (WBC) =3 000/mm3; absolute neutrophil count =1 500/mm3; or platelet count =100 000/mm3.
15. Participant has or has had unstable or clinically significant cardiovascular disease within the past 2 years.
16. Participant has uncontrolled hypertension (e.g., repeated supine diastolic blood pressure [BP] >95 mm Hg).
17. Participant has a history or presence of an abnormal ECG that is clinically significant, or evidence of acute or subacute myocardial

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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