An Open-Label Study to Evaluate Safety of long-term AL001 dosing in FTD
- Conditions
- MedDRA version: 21.1Level: PTClassification code 10068968Term: Frontotemporal dementiaSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]Frontotemporal Dementia
- Registration Number
- EUCTR2019-000138-20-DE
- Lead Sponsor
- Alector Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
PART 1:Prospective participants must meet all of the following criteria specific to their applicable participant category.
1) Completed Study AL001-1 through the Day 57 visit and did not experience AEs that the investigator deems would prevent safe participation in Study AL001-2
2) Meets 1 or more of the 6 behavioral/cognitive symptoms required for a diagnosis of possible behavioral variant frontotemporal dementia ,or has diagnosis of primary progressive aphasia
3) Prospective participant completed Study AL001-1 through the Day 43 visit and did not experience AEs that the investigator deems would prevent safe participation in Study AL001-2
4) Is a carrier of a loss of function GRN mutation causative of FTD and knows their mutation status
5) Has a CDR® plus NACC global 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
• 18 to 85 years of age
• At screening, female prospective participants must be nonpregnant and nonlactating, and at least 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 using an acceptable contraceptive method from screening until 10 weeks after the last dose of study drug. Acceptable contraception is defined as using hormonal contraceptives 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 the final dose of study treatment are located in the SoA
• Male prospective participants, if not surgically sterilized, must agree to use acceptable contraception and not donate sperm from Day 1 until 10 weeks after the last dose of study drug. 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 or an intrauterine device combined In addition, total abstinence, if in accordance with the lifestyle of the prospective participant, is acceptable. Vasectomized male participants should have received medical assessment of surgical success
•Agrees not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug
•Is willing and has the ability to comply with the study protocol requirements, in the opinion of the PI
•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)
•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 cognitive and functional abilities as well as their health throughout the study, agrees to pr
PART1:
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
• History of substance use disorder (drug or alcohol) within 2 years prior to the first study drug administration, with the exception of nicotine, as defined by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria (American Psychiatric Association 2013).
•Current acute illness or active infection requiring oral or IV antibiotics within 30 days prior to the first study drug administration that may affect safety assessments.
•History of surgery or hospitalization during the 30 days prior to first study drug administration
• History of cancer within the last 5 years with the exception of basal cell or squamous cell carcinoma.
• History or presence of intracranial tumor that is clinically relevant (e.g. glioma, cerebral metastasis).
• Positive for hepatitis B surface antigen, hepatitis C virus antibodies, or human immunodeficiency virus 1 and 2 antibodies or antigen, or history of spirochetal infection of the CNS.
• Significant kidney disease as indicated by a screening creatinine clearance <30 mL/min as calculated by the central laboratory using the Cockcroft Gault formula, which remains <30 mL/min if retested.
• 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 =1.5 × ULN, which remains above either of these limits if retested or other abnormalities in synthetic function that are clinically significant.
•Unstable or clinically significant cardiovascular disease (e.g., myocardial infarction, angina pectoris, New York Heart Association Class III or more cardiac failure) within the last 2 years.
• Uncontrolled hypertension.
• History or current abnormal ECG that is clinically significant including atrial fibrillation, complete left bundle branch block, second- or third degree heart atrioventricular block, or evidence of prior 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.
• Contraindication to lumbar dural puncture.
• Dementia or a milder, symptomatic syndrome (eg, mild cognitive impairment, mild behavioral impairment, or mild motor impairment) 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.
• 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
•Prospective participant 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 proce
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