Frontotemporal Dementia MedDRA version: 21.1 Level: PT Classification code 10068968 Term: Frontotemporal dementia System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: AL001
Product Code: AL001
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Latozinemab
CAS Number: 2376132-27-1
Current Sponsor code: AL001
Other descriptive name: AL001
C
Sponsors
Alector Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1: 1. Is a known carrier of a heterozygous loss-of-function GRN mutation causative of FTD with a global CDR® plus NACC FTLD score of 0 to 2, and: • A CDR® plus NACC FTLD-SB score =0.5 with an elevated level of serum NfL, or • A CDR® plus NACC FTLD-SB score of >0.5 with 1 or more of the 6 behavioral/cognitive symptoms required for a diagnosis of possible bvFTD (Rascovsky 2011), or a diagnosis of PPA 2. Age 25 to 85 years, inclusive, at Screening 3. At Screening, women must be nonpregnant and nonlactating, and one of the following conditions must apply: a. 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. 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, if in accordance with the lifestyle of the participant, is acceptable. c. 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. Men 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. 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. Willing to and can comply with the study protocol requirements, in the opinion of the investigator. 7. Willing and able to give informed consent. If the patient is not competent, a legally authorized representative must provide informed consent on their behalf, and the patient must provide assent, in accordance with local regulations, guidelines, and IRB or IEC. 8. Patient has the availability of a person (“study partner”) who has frequent and sufficient contact with the patient (at least 5 hours per week of in-person contact) and who can provide accurate information to the study site regarding the patient's behavior, cognitive, and functional abilities, as well as their health, throughout the study. Requirements for the study partner include: a. Willing and able to provide informed consent to participate in the study as a study partner. b. The study partner must have sufficient cognitive capacity to accurately report upon the participant’s behavior, cognitive, and functional abilities, in the opinion of the investigator. c. The study partner should be in sufficiently good general health to have a high likelihood of maintaining the same level of interaction with the participant and participation in study procedures throughout the study duration. d. The same study partner should participate throughout the duration of Part 1 of the study. If a change in study partner is necessary, the medical monitor must
Exclusion criteria
Exclusion criteria: Part 1: 1. Dementia due to a condition other than FTD including, but not limited to, Alzheimer’s disease, Parkinsonism, REM behavior disorder, dementia with Lewy bodies, Huntington disease, or vascular dementia. 2.Known mutation causative of neurodegenerative disorder(s) other than heterozygous loss-of-function GRN mutations causative of FTD. 3.Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins. 4. Signs or symptoms of progressive supranuclear palsy or bulbar dysfunction, such as postural instability, eye problems, and swallowing difficulties. 5. 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 6. Clinically significant vitamin B12 or folate deficiency (if treated, must be on a stable regimen for at least 3 months prior to first study treatment administration). 7.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.Insufficiently controlled diabetes mellitus (e.g., hemoglobin A1C =8%). 9.Any surgery (major or emergent) or hospitalization within 30 days prior to first study treatment administration. 10. History of cancer within the last 5 years with the exception of basal cell or squamous cell carcinoma. 11. 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. 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. 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 if approved by the Medical Monitor. 14. Hematologic abnormalities as indicated by hemoglobin =10 g/dL; white blood cells (WBC) =3 000/mm3; absolute neutrophil count =1,000/mm3; or platelet count =150,000/mm3. 15. Participants with hypertension who are not adequately and stably controlled as per the ACC/AHA 16. History or presence of an abnormal ECG that is clinically significant, or evidence of acute or subacute myocardial infarction or ischemia. 17. History of or concurrent clinically significant cardiovascular disease such as but not limited to myocardial infarction, angina pectoris, New York Heart Associating Class III or IV cardiac failure ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease or clinically significant electrolyte abnormalities. If the condition is stable per cardiologist, then the patient can enroll at PI discretion. Note: Participants with premature ventricular contractions are eligible to participate. 18.Clinically significant electrolyte abnormalities. 19. For participants who consent to lumbar puncture, participant has contraindication to lumbar dural puncture, including coagulop
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To evaluate the efficacy of AL001 compared with placebo in symptomatic participants as measured by CDR® plus NACC FTLD-SB. Part 2: To assess the long-term safety and tolerability of AL001 in participants who have completed Part 1 of the study;Secondary Objective: Part 1: Secondary Efficacy: To evaluate the efficacy of AL001 compared with placebo in symptomatic participants as measured by CGI-S. To evaluate the efficacy of AL001 compared with placebo in symptomatic participants as measured by CGI-I To evaluate the efficacy of AL001 compared with placebo in symptomatic participants as measured by RBANS Pharmacodynamic and Disease Biomarkers: To evaluate the treatment effect of AL001 compared with placebo as measured by pharmacodynamic and disease pathology biomarkers in the symptomatic population, the at-risk population, and all FTD participants (both symptomatic and at-risk). Safety Objective: To evaluate the safety and tolerability of AL001 compared with placebo as measured by safety assessments and antidrug antibodies (ADAs) in the symptomatic population, the at-risk population, and all FTD participants (both symptomatic and at-risk). ;Primary end point(s): Part 1: Primary Efficacy Endpoint: Target population: Symptomatic carriers of GRN mutation causative of FTD as defined by the inclusion and exclusion criteria. Variable of interest: Change from baseline to Weeks 48, 72, and 96 in the CDR® plus NACC FTLD-SB. Intercurrent events and corresponding strategy: Study treatment discontinuation/prohibited concomitant medications (Treatment Policy). All observed values of the variable of interest, regardless of whether or not the participant has discontinued treatment/taken a prohibited medication. Population-level summary variable: Percent reduction of the placebo group change from baseline across Weeks 48, 72, and 96 Part 2: Primary Endpoint: ? Incidence, nature, and severity of AEs and SAEs ? Physical examination abnormalities ? Neurological e | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: Secondary Efficacy Endpoints: To evaluate the efficacy of AL001 compared with placebo in symptomatic participants as measured by the CDR® plus NACC FTLD-SB Target population: Symptomatic carriers of a GRN mutation causative of FTD as defined by the inclusion and exclusion criteria. Variable of Interest: Change from baseline to Weeks 48, 72, and 96 on the CGI-S Intercurrent events and corresponding strategy: Study treatment discontinuation/prohibited concomitant medications (Treatment Policy). All observed values of the variable of interest, regardless of whether or not the participant has discontinued treatment/taken a prohibited medication. Population level summary variable: Percent reduction of the placebo group change from baseline across Weeks 48, 72, and 96 To evaluate the efficacy of AL001 compared with placebo in symptomatic participants as measured by CGI-S Target population: Symptomatic carriers of a GRN mutation causative of FTD as defined by the inclusion and exclusion criteria. Variable of interest: Actual values at Weeks 48, 72, and 96 on CGI-S Intercurrent events and corresponding strategy: Study treatment discontinuation/prohibited concomitant medications (Treatment Policy). All observed values of the variable of interest, regardless of whether or not the participant has discontinued treatment/taken a prohibited medication. Population-level summary variable: Percent reduction of the placebo group values at Weeks 48, 72, and 96 To evaluate the efficacy of AL001 compared with placebo as measured by RBANS Target population: Symptomatic carriers of GRN mutation causative of FTD as defined by the inclusion and exclusion criteria. Variable of interest: Change from baseline to Weeks 48, 72, and 96 in the RBANS Intercurrent events and corresponding strategy: Study treatment discontinuation/prohibited concomitant medications (Treatment Policy). All observed values of the variable of interest, regardless of whether or not the p | — |
Countries
Argentina, Australia, Belgium, Canada, France, Germany, Greece, Italy, Netherlands, Portugal, Spain, Sweden, Switzerland, Türkiye, United Kingdom, United States
Contacts
Public ContactAlector Clinical Trial Information
Alector Inc.
Outcome results
None listed