Clinical Trials

Drug Trials

Alector Phase 2 AL001-2 (INFRONT-2)

PI: David Irwin

Sub-I: Lauren Massimo, Sara Manning, Murray Grossman

Study Status: Open, No longer recruiting

Target Population: GRN+ pre-symptomatic and symptomatic

Phase: Phase 2, Open Label

General Overview: Part 1 is a 96-week evaluation of the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical effect of AL001 administered intravenously for a total of 25 doses), in asymptomatic and symptomatic carriers of loss-of-function GRN mutations causative of FTD. Part 2 is an optional OLE for eligible participants who have completed the 96-week Part 1 treatment period. The OLE period will evaluate the long-term safety and tolerability of AL001 administered at the same dose and regimen as Part 1 for up to a total of 25 doses (96-week optional OLE period).

 

Alector Phase 3 AL001-3 (INFRONT-3)

PI: David Irwin

Sub-I: Lauren Massimo, Sara Manning, Murray Grossman

Study Status: Actively Recruiting

Target Population: Males and Females Age 18-85, GRN+ pre-symptomatic and symptomatic, patient is living in the community and has a reliable study partner. Specific criteria vary based on symptomatic/pre-symptomatic status.

Phase: Phase 3, Double Blind Placebo Control 

General Overview: This is a multicenter Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of AL001 compared to placebo administered by intravenous (IV) infusion every 4 weeks in participants who are carriers of heterozygous loss-of-function GRN mutations causative of FTD. This trial is open to pre-symptomatic and symptomatic participants. Participation lasts 96 weeks, with a 2-year open label extension phase for subjects who remain eligible.

 

Genetic Therapy Trials

Prevail Trial PRV-FTD-101 (PROCLAIM)

PI: David Irwin

Sub-I: Lauren Massimo, Sara Manning, Murray Grossman

Study Status: Actively Recruiting

Target Population: FTD-GRN (behavioral-variant FTD [bvFTD], primary progressive aphasia [PPA]-FTD, FTD with corticobasal syndrome, or a combination of syndromes are allowed for enrollment)., men or women aged 30 to 80, 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. Score ≥1 and ≤15 on CDR plus NACC FTLD sum of boxes (SB). Patient is ambulatory and living in the community.

Phase: Phase 1/2 Ascending Dose

General Overview: 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 on PGRN levels of intracisternal PR006A administration in patients with FTD-GRN. Three escalating-dose cohorts (low, medium, high) are planned. The purpose is to assess the safety, tolerability, immunogenicity, and effects of PR006A on progranulin protein (PGRN) levels in plasma and/or cerebrospinal fluid (CSF), as well as its effects on biomarkers and efficacy parameters. PR006A will be administered as a single dose via suboccipital injection into the cisterna magna by a proceduralist. The procedure will be performed with the patient under general anesthesia and using imaging guidance and involves a 2-night inpatient stay and an immunosuppression regime pre and post procedure. The duration of the study is 5 years. During the first year, patients will 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.

 

PassageBio PBFT-02 (UpLIFT-D)

PI: David Irwin

Sub-I: Lauren Massimo, Sara Manning, Murray Grossman

Study Status: Actively Recruiting

Target Population: FTD-GRN (behavioral-variant FTD [bvFTD], primary progressive aphasia [PPA]-FTD, FTD with corticobasal syndrome, or a combination of syndromes are allowed for enrollment)., men or women aged 35 to 75, Patient is living in the community and has a reliable study partner.

 

Phase: Phase 1B Open-label dose escalation

General Overview: PBFT02 is a gene therapy for frontotemporal dementia intended to deliver a functional copy of the GRN gene to the brain. This study will assess the safety, tolerability, and efficacy of this treatment in patients with frontotemporal dementia and mutations in the progranulin gene (FTD-GRN). PBFT02 is an adeno-associated viral vector serotype 1 carrying GRN, the gene encoding for human progranulin, formulated as a solution for injection into the cisterna magna. Two dose cohorts are planned, with an optional third cohort. This is a global interventional, multicenter, open-label, single-arm, dose-escalation study of PBFT02 delivered as a one-time dose administered into the cisterna magna to patients with FTD-GRN. The procedure will be performed with the patient under general anesthesia or deep sedation and using imaging guidance and involves a 3-night inpatient stay and an immunosuppression regime pre and post procedure. This is a 5-year study, with a 2-year main study, followed by a 3-year safety extension.

 

For information about clinical trials (interventional research studies) at the Penn FTD Center, please reach out to our clinical trials team:

Dahlia Kamel, Clinical Trials Coordinator 

Kamel.dahlia@pennmedicine.upenn.edu 

215-662-6134 

Danielle Almstead, Clinical Trials Coordinator 

Danielle.Almstead@pennmedicine.upenn.edu 

215-662-6122