Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
Conditions
Interventions
Product Name: Recombinant AAV-9 vector expressing the human progranulin protein
Product Code: AVB-101
Pharmaceutical Form: Solution for infusion
Sponsors
AviadoBio Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, 30 to 75 years of age, inclusive, at Screening; 2. Carriers of a pathogenic granulin (GRN) mutation as confirmed by a sponsor approved genetic test; 3. Frontotemporal dementia (FTD) as evidenced by Clinical Dementia Rating (CDR)+ National Alzheimer's Coordinating Center (NACC) frontotemporal lobar degeneration (FTLD) global score of 0.5, 1.0, or 2.0; 4. Presence of 1 or more of the criteria for diagnosis of possible behavioral variant FTD or Primary Progressive Aphasia; 5. Identified, informed study partner able to support the subject for the duration of the study 6. The subject and/or legally authorized representative is able and willing to give written informed consent prior to study participation. If a subject lacks capacity to consent in the investigator’s opinion, the subject’s assent should be obtained, if required in accordance with local laws, regulations and customs, plus the written informed consent of a legal representative should be obtained. In countries where local laws, regulations, and customs do not permit subjects who lack capacity to consent to participate in this study, they will not be enrolled. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. Classification of the mutation in the GRN gene as “not pathogenic,” “likely benign variant,” or “benign variant” in the Alzheimer’s Disease and Frontotemporal Dementia Mutation Database; 2. Severe dementia that precludes ability to comply with study procedures and/or poses unacceptable safety risk to the subject (i.e. CDR+ NACC FTLD score of 3.0); 3. Concurrent disease that may cause cognitive impairment unrelated to mutations in the GRN gene, such as other causes of dementia, neurosyphilis, hydrocephalus, stroke, small vessel ischemic disease, uncontrolled hypothyroidism, or vitamin B12 deficiency; 4. Clinically significant abnormality on magnetic resonance imaging (MRI) at Screening considered to be a contraindication to intrathalamic infusion; 5. Surgically significant pattern of brain atrophy on MRI at Screening that interferes with planned surgical trajectory; 6. Previous treatment with any gene or cell therapy; 7. Previous treatment with any investigational medicinal product within 60 days or 5 half-lives (whichever is longer) prior to study drug dosing; 8. Concomitant disease or treatment which, in the opinion of the Investigator, may pose an unacceptable safety risk to the participant or interfere with study conduct or the subject's ability to comply with study procedures; 9. Contraindications to MRI as per local guidelines; 10. Contraindications to gadolinium-based contrast agents per local guidelines; 11. Contraindications to general anesthesia for a period of up to 10 hours and/or cardiopulmonary disorders that would result in a higher ASA risk classification; 12. Contraindications to lumbar puncture as per local guidelines;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of a one-time, bilateral, intrathalamic administration of AVB-101 in subjects with FTD-GRN.;Secondary Objective: To evaluate the preliminary clinical and biomarker measures of efficacy of a one-time, bilateral, intrathalamic administration of AVB-101 in subjects with FTD-GRN.;Primary end point(s): Over a 26-week initial and 5year total follow up period: • Number and incidence of AEs, SAEs, and clinically meaningful laboratory test abnormalities; • Change from baseline in vital signs, ECG parameters, and physical and neurological examinations, and MMSE • Change from baseline in mini-mental state examination (MMSE); • Change from baseline in biochemistry and hematology safety laboratory tests; • Time to achieve clearance of vector genomes in plasma and semen (male only) • Incidence of treatment emergent suicidal ideation or behavior as measured using the C-SSRS. • Change from baseline in MRI including oedema, inflammation, pre-symptomatic/symptomatic hemorrhage and other structural changes;Timepoint(s) of evaluation of this end point: 26 weeks and 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Over a 26-week initial and 5-year total follow up period: • Change from baseline in PGRN protein levels in CSF and blood; Over a 52-week initial and 5-year total follow up period: • Change from baseline in NfL levels in CSF and blood Over a 5-year follow up period: • Change from baseline in CDR+NACC FTLD-SB score; • Change in CGI C, PGI-C, CaGI-C;Timepoint(s) of evaluation of this end point: 26 weeks and 5 years | — |
Countries
Belgium, France, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trial Management
Medpace
Outcome results
None listed