AVB-101 for Frontotemporal dementia with progranulin (GRN) mutations

Inclusion criteria

• {"criterion_text":"- 1. Are male or female, 30 to 75 years of age, inclusive, at Screening\n- 9. Have an identified, informed study partner who is able and willing to support the subject’s participation in the study and to provide assessments of the subject during the study (separate, written informed consent to be obtained from the study partner for their participation, where required to do so by the relevant country’s competent authorities).\n- 2. Are carriers of a pathogenic granulin (GRN) mutation (ie, heterozygous loss-of-function mutation causative of FTD) as confirmed by a Sponsor approved genetic test.\n- 3. Have 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\n- 4. Have presence of 1 or more of the criteria for diagnosis of possible behavioral variant FTD or primary progressive aphasia\n- 5. For women of childbearing potential, must have a negative serum pregnancy test at Screening, a negative urine dipstick, and not be breastfeeding within 2 weeks prior to treatment\n- 6. Are willing to practice a highly effective birth control method as outlined in the Protocol if the subject or partner is of childbearing potential\n- 7. Able and willing to comply with all procedures and the study visit schedule as outlined in the Protocol\n- 8. Able and willing to give written informed consent prior to study participation, and agree to designate a legal representative to act on their wishes to continue participation should they lose capacity to consent at some point during the study OR If, in the Investigator’s opinion, the subject lacks capacity to consent, written informed consent of their legal representative must be obtained in accordance with local laws, regulations, and/or customs. In countries where local laws, regulations, and/or customs do not permit subjects who lack capacity to consent to participate in this study, these subjects will not be enrolled"}

Exclusion criteria

• {"criterion_text":"- 1. Have a classification of the mutation in the GRN gene as “not pathogenic,” “likely benign variant,” or “benign variant”\n- 18. Have the presence of an implanted deep brain stimulation device, ventriculoperitoneal or other cerebrospinal fluid (CSF) shunt, or other implanted device\n- 2. Have severe dementia, defined as CDR + NACC FTLD global score of 3.0, or other symptoms that preclude the ability to comply with study procedures and/or pose unacceptable safety risk to the subject\n- 19. Have evidence of suicide risk, as assessed by the Columbia-Suicide Severity Rating Scale, defined as either a suicide attempt within 6 months prior to Screening or have a significant risk of suicide as judged by the Investigator\n- 20. Have a known or suspected intolerance or hypersensitivity to the study drug or any of the stated ingredients.\n- 3. Have any 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\n- 4. Have a clinically significant abnormality on magnetic resonance imaging (MRI) at Screening considered to be a contraindication to intrathalamic infusion\n- 5. Have a surgically significant pattern of brain atrophy on MRI at Screening that in the determination of the neurosurgeon interferes with planned neurosurgical trajectory\n- 6. Have had previous treatment with any gene or cell therapy\n- 7. Have had previous treatment with any investigational medicinal product within 60 days or 5 half-lives (whichever is longer) prior to study drug treatment\n- 8. Have had a concomitant disease, any clinically significant laboratory abnormality, or treatment which, in the opinion of the Investigator, may pose an unacceptable safety risk to the subject or interfere with study conduct or the subject's ability to comply with study procedures\n- 10. Have any contraindications to MRI as per local guidelines\n- 9. Have a malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated\n- 11. Have any contraindications to gadolinium-based contrast agents per local guidelines\n- 12. Have any contraindications to general anesthesia for a period of up to 10 hours and/or cardiopulmonary disorders that would result in higher American Society of Anesthesiology risk classification\n- 13. Have any contraindications to lumbar puncture as per local guidelines\n- 14. Have been hospitalized for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned procedure during the study\n- 15. Are using anticoagulants at Screening, or will have an anticipated need during the period of treatment. Antiplatelet therapies are acceptable concomitant medications if they can be stopped at least 48 hours prior to treatment\n- 16. Have a positive drug screen for drugs of abuse\n- 17. Have a history of substance abuse disorder"}

Primary endpoints

• {"endpoint_text":"- 1.1. Over a 26-week initial and 5-year total follow-up period: - Number and incidence of AEs, SAEs, and clinically meaningful laboratory test abnormalities;","definition_or_measurement_approach":"Assessment of number and incidence of adverse events (AEs), serious adverse events (SAEs), and clinically meaningful laboratory test abnormalities recorded over an initial 26-week period and total follow-up of 5 years."}
• {"endpoint_text":"- 1.2. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in vital signs, ECG parameters, and physical and neurological examinations","definition_or_measurement_approach":"Change from baseline measures in vital signs, ECG parameters, and findings from physical and neurological examinations assessed over the 26-week initial and 5-year total follow-up period."}
• {"endpoint_text":"- 1.3. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in the MMSE;","definition_or_measurement_approach":"Change from baseline in Mini-Mental State Examination (MMSE) scores measured during the initial 26 weeks and across total 5-year follow-up."}
• {"endpoint_text":"- 1.4. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in biochemistry and hematology safety laboratory tests","definition_or_measurement_approach":"Change from baseline in specified biochemistry and hematology safety laboratory parameters over the stated follow-up periods."}
• {"endpoint_text":"- 1.5. Over a 26-week initial and 5-year total follow-up period: - Incidence of treatment-emergent suicidal ideation or behavior as measured on the C-SSRS;","definition_or_measurement_approach":"Incidence of treatment-emergent suicidal ideation or behavior assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS) over the initial 26 weeks and 5-year follow-up."}
• {"endpoint_text":"- 1.6. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in MRI results including edema, inflammation, asymptomatic/symptomatic hemorrhage, and other structural changes.","definition_or_measurement_approach":"Change from baseline on MRI imaging assessments including evaluation for edema, inflammation, hemorrhage (asymptomatic/symptomatic) and other structural brain changes during the initial 26 weeks and over 5 years."}

Secondary endpoints

• {"endpoint_text":"- 1.1. Over a 26-week initial and 5-year total follow-up period: - Change from baseline in PGRN protein levels in CSF and blood.","definition_or_measurement_approach":"Change from baseline in progranulin (PGRN) protein concentrations measured in cerebrospinal fluid (CSF) and blood over initial 26 weeks and total 5-year follow-up."}
• {"endpoint_text":"- 1.2. Over a 5-year follow-up period: - Change from baseline in CDR + NACC FTLD-SB score; and - Change in CGI-C, PGI-C, and CaGI-C","definition_or_measurement_approach":"Change from baseline in CDR + NACC FTLD-SB score and changes in clinician/global and patient/caregiver global impression scales (CGI-C, PGI-C, CaGI-C) measured over 5-year follow-up."}

Methods

• GP Letter: targeted letters to general practitioners to identify potential participants (country-specific GP letters available e.g. EN, FR, PL as recruitment documents).
• HCP / Dear Colleague letters and HCP flyers: outreach to healthcare professionals and neurologists to refer eligible patients.
• Participant brochures, participant handbook, participant posters and flyers: printed materials for potential participants and caregivers (available in multiple languages and country-specific versions).
• Social media kit and social media advertisement: digital outreach via social media channels (country-specific social media materials available).
• Site website and site newsletter materials: site-level online recruitment materials and study information pages.
• Study PowerPoint and conference flyers: materials for presentations to professional audiences and patient groups.
• Patient Consent and Support Flow / Patient screening schedules: structured patient engagement and support processes including consent pathways and scheduling materials.
• Clincierge/Clincierge travel and pay portal guides: centralized travel and participant support services for participants (logistics support).

Belgium

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

13-02-2026

Processing Time Days

675

Number Of Sites

1

Number Of Participants

2

Poland

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

678

Number Of Sites

8

Number Of Participants

8

Italy

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

04-03-2026

Processing Time Days

694

Number Of Sites

1

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

17-02-2026

Processing Time Days

679

Number Of Sites

3

Number Of Participants

1

Netherlands

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

17-02-2026

Processing Time Days

679

Number Of Sites

1

Number Of Participants

2

Sweden

Earliest CTIS Part Ii Submission Date

09-04-2024

Latest Decision Or Authorization Date

13-02-2026

Processing Time Days

675

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Aviadobio Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

Multiple sponsor support roles (codes include 1,2,4,5,6,7,8,12,13,15 - translations noted)

Name

Medidata Solutions Inc.

Responsibilities

Data platform/clinical data (sponsor duties code 6)

Name

Ixico Technologies Limited

Responsibilities

Medical image analysis/review - MRI

Name

Charles River Laboratories Inc.

Responsibilities

Laboratory services (code 4)

Name

Northern Biomolecular Services, Corp

Responsibilities

Vector shedding qPCR testing

Name

Gray Consulting Inc.

Responsibilities

Patient travel arrangements

Name

Clearpoint Neuro Inc.

Responsibilities

Provision of ClearPoint navigation system

Name

Transperfect Translations International Inc.

Responsibilities

Translation/interpretation services

Name

Blueprint Genetics Oy

Responsibilities

Genetic testing

Third parties

• {"country":"United Kingdom","full_name":"Ixico Technologies Limited","duties_or_roles":"Medical image analysis/ review - MRI","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"Sponsor duties codes: 1,12,13,15 (Translations),2,4,5,6,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties code: 6","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Northern Biomolecular Services, Corp","duties_or_roles":"Vector Shedding (qPCR)","organisation_type":"Industry"}
• {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"Patient travel arrangements","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Blueprint Genetics Oy","duties_or_roles":"Genetic testing","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"Sponsor duties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Interpretation Service","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clearpoint Neuro Inc.","duties_or_roles":"ClearPoint navigation system","organisation_type":"Pharmaceutical company"}