A Phase 1/2 Study with Ascending Dose in order to Evaluate the Safety and Effects on Progranulin Levels of investigational product under code LY3884963 in Patients with Fronto-Temporal Dementia with Progranulin Mutations (FTD-GRN) (PROCLAIM)
- Conditions
- Fronto-Temporal Dementia with Progranulin Mutations (FTD-GRN)MedDRA version: 21.1Level: PTClassification code: 10068968Term: Frontotemporal dementia Class: 100000004852Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- CTIS2022-502942-29-01
- Lead Sponsor
- Prevail Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 35
Men or women aged 30 to 85 years (inclusive), at the time of informed consent., Patient has a reliable study partner/informant (e.g., family member, friend) willing and able to participate in the study as a source of information on the patient’s health status and cognitive and functional abilities (including providing input into the rating scales)., Patient is generally ambulatory and not dependent on a walker or wheelchair., Patient is living in the community (i.e. not in a nursing home); some levels of assisted living may be permitted at the Investigator's discretion., Pneumococcal pneumonia and shingles vaccines are required within 10 years of Screening (allowed to be performed during Screening but must be given at least 4 weeks prior to initiation of immunosuppressant regimen)., Body weight range of =40 kg (88 lb) to =110 kg (242 lb) and a body mass index (BMI) of 18 to 34 kg/m2., Has symptomatic frontotemporal dementia (FTD), including mild behavioral, cognitive, motor or language impairment per Investigator’s assessment (behavioral-variant FTD, primary progressive aphasia-FTD, FTD with corticobasal syndrome, or a combination of syndromes are allowed for enrollment)., Score =0.5 and =15 on CDR plus NACC FTLD sum of boxes., Stable use of background medications at least 8 weeks prior to LY3884963 dosing., Carrier of a pathogenic progranulin gene (GRN) mutation confirmed by the central laboratory., Negative screening test for Mycobacterium tuberculosis (MTB) or documented negative MTB test within 1 year prior to Screening., Age- and gender-appropriate cancer screenings are up to date and completed per the Investigator's judgment and local standard of care prior to Screening., Patient and/or patient’s legally authorized representative (LAR) (where applicable by local regulation) has the ability to understand the purpose and risks of the study, and provide written informed consent and authorization to use protected health information in accordance with national and local privacy regulations.
Diagnosis of a significant central nervous system (CNS) disease other than FTD that may be a cause for the patient's FTD symptoms or may confound study objectives., Use of blood thinners (e.g., warfarin, heparin, and novel oral anticoagulants) in the 2 weeks prior to Screening or the anticipated need to initiate blood thinners during the study. Antiplatelet therapies (prophylactic aspirin, clopidogrel) are acceptable if the patient is medically able to temporarily stop 48 hours to 7 days (depending on the antiplatelet medication used) prior to and at least 48 hours after ICM injection and LP. Note: the use of blood thinners as part of prophylaxis or treatment of an emergent VTE or another AE during the study does not exclude the patient, unless there is a baseline high risk of thromboembolic events, and use of blood thinners is highly anticipated in the opinion of the Investigator., Contraindications or intolerance to imaging methods (MRI, MRA, and/or computed tomography [CT]), including claustrophobia and intolerance to contrast agents used for MRI, MRA, or CT (including, but not limited to, gadolinium contrast agents and iohexol)., Contraindications to general anesthesia or deep sedation., Positive urine test for drugs of abuse (including opiates, amphetamines, cocaine, barbiturates, and phencyclidine) without prescription at Screening and on Day -1., Brain or cervical spine magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) imaging indicating clinically significant abnormality considered to prevent intracisternal magna (ICM) injection., Hypersensitivity or contraindications to corticosteroid, and/or sirolimus use (including, but not limited to, osteoporosis with vertebral fractures within 1 year prior to Screening, poorly controlled diabetes, uncontrolled hypertension, and uncontrolled hyperlipidemia or hypercholesterolemia per Investigator’s assessment)., Clinical evidence of peripheral symmetric sensory polyneuropathy (stable sensory mononeuropathies and radiculopathies are not exclusionary)., Concomitant disease or condition within 6 months of Screening that could interfere with, or treatment of which might interfere with, the conduct of the study or that would, in the opinion of the Investigator, pose an unacceptable safety risk to the patient or interfere with the patient's ability to comply with study procedures., Clinically significant abnormalities in laboratory test results at Screening., Participation within 3 months prior to Screening in another therapeutic investigational drug or device study with purported disease-modifying effects on FTD, unless it can be documented that the patient received placebo only., Any type of prior gene or cell therapy., Live vaccines in the 4 weeks prior to Screening. Note: Pneumococcal vaccine and/or shingles vaccine administration is allowed at least 4 weeks prior to initiation of immunosuppressant regimen.
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