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Trial record 1 of 52 for:    prevail therapeutics
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Phase 1/2 Clinical Trial of PR006 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04408625
Recruitment Status : Not yet recruiting
First Posted : May 29, 2020
Last Update Posted : May 29, 2020
Sponsor:
Information provided by (Responsible Party):
Prevail Therapeutics

Brief Summary:
Study PRV-FTD101 is a Phase 1/2, multi-center, open-label ascending dose, first-in-human study that will evaluate the safety and effect of intra-cisternal PR006 administration on progranulin protein (PGRN) levels in patients with frontotemporal dementia with progranulin mutations (FTD-GRN). Three escalating dose (low dose, medium dose and high dose) cohorts are planned. The duration of the study is 5 years. During the first year, patients with be evaluated for the effect of PR006 on safety, tolerability, immunogenicity, biomarkers, and efficacy. Patients will follow up for an additional 4 years to monitor safety and changes on selected biomarkers and clinical outcomes.

Condition or disease Intervention/treatment Phase
Frontotemporal Dementia Biological: PR006 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Ascending Dose Study to Evaluate the Safety and Effects on Progranulin Levels of PR006A in Patients With Fronto-Temporal Dementia With Progranulin Mutations (FTD-GRN)
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : December 2027
Estimated Study Completion Date : December 2027


Arm Intervention/treatment
Experimental: Low dose Biological: PR006
Participants will receive a single dose of PR006, administered intracisternally

Experimental: Medium dose Biological: PR006
Participants will receive a single dose of PR006, administered intracisternally

Experimental: High dose Biological: PR006
Participants will receive a single dose of PR006, administered intracisternally




Primary Outcome Measures :
  1. Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 5 years ]
  2. Number of adverse reactions (ARs) and suspected ARs [ Time Frame: 5 years ]
  3. Number of serious ARs and serious suspected ARs [ Time Frame: 5 years ]
  4. Change in PGRN (progranulin protein) levels in blood [ Time Frame: 5 years ]
  5. Change in PGRN levels in CSF (cerebrospinal fluid) [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. Change in CDR plus NACC FTLD (Clinical Dementia Rating staging instrument plus National Alzheimer's Coordinating Center frontotemporal lobar degeneration domains [ Time Frame: 5 years ]
  2. Change in NFL (neurofilament light chain) levels in blood [ Time Frame: 5 years ]
  3. Change in NFL levels in CSF [ Time Frame: 5 years ]
  4. Immunogenicity of AAV9 in blood as measured by AAV9 antibody levels and enzyme-linked immunospot reactivity [ Time Frame: Up to Month 24 ]
  5. Immunogenicity of AAV9 in CSF as measured by AAV9 antibody levels and enzyme-linked immunospot reactivity [ Time Frame: Up to Month 24 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body weight range of ≥40 kg (88 lb) to ≤110 kg (242 lb) and a BMI of 18 to 34 kg/m2.
  • Has symptomatic frontotemporal dementia (FTD) per investigator assessment.
  • Stable use of background medications at least 8 weeks prior to investigational product dosing.
  • Carrier of a pathogenic GRN (progranulin gene) mutation.
  • 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.
  • Patient and/or patient's legally authorized representative has the ability to understand the purpose and risks of the study, and provide written informed consent and authorization to use protected health information.
  • 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..
  • Women of non-childbearing potential must be either surgically sterile or postmenopausal.
  • Men and women of childbearing potential must use a highly effective method of contraception for the duration of the study.
  • Men must agree to abstain from sperm donation for the duration of the study.
  • Women must agree to abstain from egg donation for the duration of the study.
  • Women of childbearing potential cannot be pregnant or lactating/breastfeeding, and must have a negative serum pregnancy test at screening.
  • Patient is not dependent on walker or wheelchair.
  • Patient is living in the community (i.e. not in nursing home); some levels of assisted living may be permitted at the discretion of the investigator.

Exclusion Criteria:

  • Diagnosis of a significant CNS (central nervous system) disease other than frontotemporal dementia (FTD) that may cause FTD symptoms or confound study objectives.
  • Brain magnetic resonance image (MRI) / magnetic resonance angiography (MRA) showing clinically significant abnormality considered to prevent intracisternal injection.
  • Contraindications to corticosteroid use or uncontrolled hypertension.
  • 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 laboratory test result abnormalities assessed 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.
  • Immunizations (live vaccines) in the 4 weeks prior to screening. Pneumococcal vaccine administration is allowed during screening.
  • Use of blood thinners in the 2 weeks prior to screening, or anticipated use of blood thinners during the study. Antiplatelet therapies may be acceptable.
  • Contraindications or intolerance to imaging methods (MRI, CT) and intolerance to contrast agents.
  • Contraindications to general anesthesia or deep sedation.
  • Positive urine test for drugs of abuse (including opiates, benzodiazepines, amphetamines, cocaine, barbiturates and phencyclidine) without prescription at screening and day -1.

Other protocol-defined inclusion/exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04408625


Contacts
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Contact: Prevail Therapeutics (917) 336-9310 patients@prevailtherapeutics.com

Locations
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United States, California
UCSF Memory and Aging Center, 350 Parnassus Ave, Suite 706
San Francisco, California, United States, 94117
Contact: Hannah Wiest    415-476-0671    hannah.wiest@ucsf.edu   
Contact: Mary Koestler    415-476-0661    mary.koestler@ucsf.edu   
United States, Florida
Mayo Clinic, 4500 San Pablo Road,
Jacksonville, Florida, United States, 32224
Bioclinica Orlando, 100 West Gore Street, Suite 202
Orlando, Florida, United States, 32806
Contact: Jessica Garaycoa    689-216-3100    Jessica.Garaycoa@ppdi.com   
United States, Pennsylvania
University of Pennsylvania, The Penn FTD Center, 3 West Gates
Philadelphia, Pennsylvania, United States, 19104
Contact: Frewine Ogbaselase    215-662-6134    Frewine.Ogbaselase@pennmedicine.upenn.edu   
Sponsors and Collaborators
Prevail Therapeutics
Investigators
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Study Director: Olga Uspenskaya-Cadoz, MD, PhD Prevail Therapeutics
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Responsible Party: Prevail Therapeutics
ClinicalTrials.gov Identifier: NCT04408625    
Other Study ID Numbers: PRV-FTD101
First Posted: May 29, 2020    Key Record Dates
Last Update Posted: May 29, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prevail Therapeutics:
Fronto-Temporal Dementia
Frontotemporal Dementia
Progranulin Mutations
FTD-GRN
Gene Therapy
Dementia Gene Therapy
AAV9
Additional relevant MeSH terms:
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Dementia
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Neurodegenerative Diseases
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms