Authorised Phase I and Phase II (Integrated)- First administration to humans Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)

Ph1/2 study of AVB-101 in Subjects with Frontotemporal Dementia with Progranulin Mutations (FTD-GRN)

EU CTIS ID: 2023-509444-10-00

What this study is testing

To evaluate the safety and tolerability of a one-time, intrathalamic administration of AVB-101 in subjects with FTD-GRN.

Phase I and Phase II (Integrated)- First administration to humans

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Are male or female, 30 to 75 years of age, inclusive, at Screening
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).
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.
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
4. Have presence of 1 or more of the criteria for diagnosis of possible behavioral variant FTD or primary progressive aphasia
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

You likely can't join if

1. Have a classification of the mutation in the GRN gene as “not pathogenic,” “likely benign variant,” or “benign variant”
18. Have the presence of an implanted deep brain stimulation device, ventriculoperitoneal or other cerebrospinal fluid (CSF) shunt, or other implanted device
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
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
20. Have a known or suspected intolerance or hypersensitivity to the study drug or any of the stated ingredients.
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

See the full eligibility criteria

Who can join

1. Are male or female, 30 to 75 years of age, inclusive, at Screening
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).
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.
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
4. Have presence of 1 or more of the criteria for diagnosis of possible behavioral variant FTD or primary progressive aphasia
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
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
7. Able and willing to comply with all procedures and the study visit schedule as outlined in the Protocol
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

What rules you out

1. Have a classification of the mutation in the GRN gene as “not pathogenic,” “likely benign variant,” or “benign variant”
18. Have the presence of an implanted deep brain stimulation device, ventriculoperitoneal or other cerebrospinal fluid (CSF) shunt, or other implanted device
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
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
20. Have a known or suspected intolerance or hypersensitivity to the study drug or any of the stated ingredients.
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
4. Have a clinically significant abnormality on magnetic resonance imaging (MRI) at Screening considered to be a contraindication to intrathalamic infusion
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
6. Have had previous treatment with any gene or cell therapy
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
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
10. Have any contraindications to MRI as per local guidelines
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
11. Have any contraindications to gadolinium-based contrast agents per local guidelines
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
13. Have any contraindications to lumbar puncture as per local guidelines
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
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
16. Have a positive drug screen for drugs of abuse
17. Have a history of substance abuse disorder

The study team makes the final eligibility decision.

Where it's taking place

United States
United Kingdom
Canada

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; United Kingdom; Canada. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.