A Study to Evaluate Effectiveness and Safety of AL001 in Frontotemporal Dementia


About this study

The primary purpose of this study is to evaluate the efficacy of AL001 compared with placebo in carriers of progranulin gene (GRN) mutations causative of frontotemporal dementia (FTD) as measured by the Clinical Dementia Rating Dementia Staging Instrument PLUS National Alzheimer’s Disease Coordinating Center frontotemporal lobar degeneration Behavior & Language Domains Sum of Boxes (CDR® plus NACC FTLD-SB).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • 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 (Gorno-Tempini 2011).
  • Age 25 to 85 years, inclusive, at Screening.
  • At Screening, women must be nonpregnant and nonlactating, and one of the following conditions must apply:
    • 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]);
    • 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;
    • 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.
  • 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.
  • 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.
  • Willing to and can comply with the study protocol requirements, in the opinion of the investigator.
  • 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 institutional review board (IRB) or independent ethics committee (IEC).
  • 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:
    • Willing and able to provide informed consent to participate in the study as a study partner;
    • 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;
    • 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;
    • 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 be contacted;
    • Study partner agrees to provide information at investigational site visits that require partner input for COA completion;
    • Study partner agrees to accompany the participant at COA visits, as follows:
      • At-risk participants (CDR® plus NACC FTLD-SB score ≤ 0.5) require the study partner at the COA visits only;
      • . − Symptomatic participants (CDR® plus NACC FTLD-SB score > 0.5) require the study partner at each visit;
      • At-risk participants who become symptomatic (CDR® plus NACC FTLDSB > ) during the study treatment period require the study partner at each visit moving forward through Study Completion. Inclusion criteria applicable to those participants participating in the optional Winterlight Labs Speech Assessment (WLA) only:
      • Has available and willing study partner to administer the WLA;
      • Has WiFi access in their residence or WiFi access in a private area where the testing can take place;
      • Participants and study partners must be proficient in English, Spanish, French, or German in the investigator’s opinion.

Exclusion Criteria:

  • 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.
  • Known mutation causative of neurodegenerative disorder(s) other than heterozygous loss-of-function GRN mutations causative of FTD.
  • Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
  • Signs or symptoms of progressive supranuclear palsy or bulbar dysfunction, such as postural instability, eye problems, and swallowing difficulties.
  • 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 (American Psychiatric Association 2013).
  • Currently has or has had an acute illness that requires or required systemic antibiotics within 30 days prior to first study treatment administration.
  • 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).
  • 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).
  • Insufficiently controlled diabetes mellitus (e.g., hemoglobin A1C ≥ 8%).
  • Any surgery (major or emergent) or hospitalization within 30 days prior to first study treatment administration.
  • History of cancer within the last 5 years with the exception of basal cell or squamous cell carcinoma.
  • 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.
  • Significant kidney disease as indicated by either of the following:
    • Estimated glomerular filtration rate (eGFR) 95 mm Hg or systolic BP > 150 mm Hg) at screening.
  • History or presence of an abnormal ECG that is clinically significant, including complete left bundle branch block, second- or third-degree atrioventricular block, or evidence of acute or subacute myocardial infarction or ischemia.
  • History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy) or clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia).
    • Note: Participants with premature ventricular contractions are eligible to participate.
  • For participants who consent to lumbar puncture, participant has contraindication to lumbar dural puncture, including coagulopathy, concomitant anticoagulation medication (except for a platelet inhibitor such as aspirin), thrombocytopenia, or other factor(s) that precludes safe lumbar puncture.
  • History or presence of clinically evident vascular disease potentially affecting the brain (e.g., clinically significant carotid or vertebral artery stenosis or plaque; cerebral hemorrhage or infarct greater than 1 cm3; 3 or more lacunar infarcts in any location; cerebral contusion; encephalomalacia; intracranial aneurysm; arteriovenous malformation; subdural hematoma); hydrocephalus; space-occupying lesions (e.g., abscess or brain tumor such as meningioma) that have the potential to affect cognitive function; or intracranial tumor that is clinically relevant (e.g., glioma, cerebral metastasis).
  • History of a clinically significant, persistent neurologic deficit, structural brain damage, or CNS trauma.
  • Resides in a skilled nursing facility, convalescent home, or long-term care facility at screening; or requires continuous nursing care (i.e., > 3 months).
  • Unable to tolerate MRI procedures (e.g., due to anxiety or claustrophobia) or has a contraindication to MRI, including, but not limited to, the presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or body that are not compatible with an MRI scan; or any other clinical history or examination finding that would pose a potential hazard in combination with MRI.
  • Has a medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise their ability to comply with the protocol-required testing or procedures, or compromise the participant’s well-being, safety, or clinical interpretability.

Eligibility last updated 1/4/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Bradley Boeve, M.D.

Open for enrollment

Contact information:

Kevin Nelson

(507) 284-9295


More information


Publications are currently not available

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