Phase 1/2 Clinical Trial of PR006 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
Phase 1/2 Clinical Trial of PR006 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
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.
Inclusion Criteria:

 -  Body weight range of ≥40 kg (88 lbs) 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..

 -  Patient is not dependent on a 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.

 -  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
 administration of immunosuppressant at the start of the study).

 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.

 -  Hypersensitivity or contraindications to corticosteroid and/or sirolimus use.

 -  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
 and shingles 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.

 Other protocol-defined inclusion/exclusion criteria may apply