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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04408625




Registration number
NCT04408625
Ethics application status
Date submitted
21/05/2020
Date registered
29/05/2020
Date last updated
24/05/2024

Titles & IDs
Public title
Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
Scientific title
A Phase 1/2 Ascending Dose Study to Evaluate the Safety and Effects on Progranulin Levels of LY3884963 in Patients With Fronto-Temporal Dementia With Progranulin Mutations (FTD-GRN)
Secondary ID [1] 0 0
J4B-MC-OKAA (PRV-FTD101)
Universal Trial Number (UTN)
Trial acronym
PROCLAIM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Frontotemporal Dementia 0 0
Condition category
Condition code
Neurological 0 0 0 0
Dementias
Neurological 0 0 0 0
Alzheimer's disease
Mental Health 0 0 0 0
Other mental health disorders
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - LY3884963
Treatment: Drugs - Methylprednisolone
Treatment: Drugs - Optional Sirolimus
Treatment: Drugs - Optional Prednisone

Experimental: Initial Cohort - Low dose -

Experimental: Initial Cohort - Medium dose -

Experimental: Bridging Cohort - Low dose - Participants enrolled in the Bridging Cohort will be assigned to either low or medium dose in an alternating manner

Experimental: Bridging Cohort - Medium dose - Participants enrolled in the Bridging Cohort will be assigned to either low or medium dose in an alternating manner


Other interventions: LY3884963
Participants will receive a single dose of LY3884963, administered intra cisterna magna

Treatment: Drugs: Methylprednisolone
IV pulses every 2 weeks in the first 3 months.

Treatment: Drugs: Optional Sirolimus
At the investigators discretion following steroid tolerability issues, patients may receive a loading dose, followed by maintenance dose, followed by dose tapering; administered as concomitant medication

Treatment: Drugs: Optional Prednisone
If needed and at the investigator discretion, Oral Prednisone may be added to the immunosuppression regimen
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events Leading to discontinuation
Timepoint [1] 0 0
5 Years
Primary outcome [2] 0 0
Sum of adverse reactions (ARs) and suspected ARs
Timepoint [2] 0 0
5 years
Primary outcome [3] 0 0
Sum of serious ARs and serious suspected ARs
Timepoint [3] 0 0
5 years
Primary outcome [4] 0 0
Incidence of procedure or treatment-emergent AEs
Timepoint [4] 0 0
5 years
Primary outcome [5] 0 0
Change in PGRN immunogenicity in blood
Timepoint [5] 0 0
Baseline and Month 12
Primary outcome [6] 0 0
Change in PGRN immunogenicity in CSF
Timepoint [6] 0 0
Baseline and Month 12
Primary outcome [7] 0 0
Change in AAV9 immunogenicity in blood
Timepoint [7] 0 0
Baseline and Month 12
Primary outcome [8] 0 0
Change in AAV9, PGRN, and NfL immunogenicity in CSF
Timepoint [8] 0 0
Baseline and Month 12
Primary outcome [9] 0 0
Change in PGRN levels in blood
Timepoint [9] 0 0
Baseline and Month 12
Primary outcome [10] 0 0
Change in PGRN levels in CSF
Timepoint [10] 0 0
Baseline and Month 12
Secondary outcome [1] 0 0
Change in CDR plus NACC FTLD
Timepoint [1] 0 0
Baseline and Month 12
Secondary outcome [2] 0 0
Change in NfL levels in blood
Timepoint [2] 0 0
Baseline and Month 12
Secondary outcome [3] 0 0
Change in NfL levels in CSF
Timepoint [3] 0 0
Baseline and Month 12

Eligibility
Key inclusion criteria
- Men or women aged 30 to 85 years (inclusive), at the time of informed consent.

- 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), including mild behavioral, cognitive,
motor or language impairment per Investigator's assessment (behavioral-variant FTD,
primary progressive aphasia-FTD, FTD with corticobasal syndrome, or a combination of
syndromes are allowed for enrollment).

- Score =0.5 and =15 on CDR plus NACC FTLD sum of boxes.

- Stable use of background medications at least 8 weeks prior to LY3884963 dosing.

- Carrier of a pathogenic progranulin gene (GRN) mutation.

- Negative screening test for Mycobacterium tuberculosis (MTB) or documented negative
MTB test within 1year prior to screening.

- Age- and gender-appropriate cancer screenings are up-to-date and completed.

- 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
initiation of immunosuppressant regimen).
Minimum age
30 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 or cervical spine magnetic resonance image (MRI)/MRA imaging showing clinically
significant abnormality considered to prevent intracisternal magna (ICM) 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.

- Live vaccines in the 4 weeks prior to Screening. NOTE: Pneumococcal vaccine and/or
shingles vaccine administration is allowed at least 4 weeks prior to initiation of
immunosuppressant regimen.

- Use of blood thinners in the 2 weeks prior to screening, or anticipated use of blood
thinners during the study. Antiplatelet therapies are acceptable if the patient is
medically able to temporarily stop 48 hours to 7 days (depending on the antiplatelet
medication used) prior to and at least 48 hours after ICM injection and LP. Note: the
use of blood thinners as part of prophylaxis or treatment of an emergent VTE or
another AE during the study does not exclude the patient, unless there is a baseline
high risk of thromboembolic events, and use of blood thinners is highly anticipated in
the opinion of the Investigator.

- Contraindications or intolerance to imaging methods (MRA, MRI, and/or computed
tomography [CT]), including claustrophobia and intolerance to contrast agents used for
MRI, MRA, or CT (including, but not limited to, gadolinium contrast agents and
iohexol).

- Contraindications to general anesthesia or deep sedation.

- Positive urine test for drugs of abuse (including opiates, amphetamines, cocaine,
barbiturates, and phencyclidine) without prescription at Screening and on Day 1.

Other protocol-defined inclusion/exclusion criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/08/2029
Actual
Sample size
Target
23
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital, Brain & Mind Research Institute, 94 Mallet Street - Camperdown
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
France
State/province [4] 0 0
Paris
Country [5] 0 0
Spain
State/province [5] 0 0
Barcelona
Country [6] 0 0
Spain
State/province [6] 0 0
San Sebastian
Country [7] 0 0
United Kingdom
State/province [7] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Prevail Therapeutics
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Study J4B-MC-OKAA 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 LY3884963 administration on
progranulin protein (PGRN) levels in patients with frontotemporal dementia with progranulin
mutations (FTD-GRN). Two escalating dose (low dose and medium dose) cohorts are planned, as
well as one bridging cohort which will allocate patients to receive either low or medium
dose. The duration of the study is 5 years. During the first year, patients will be evaluated
for the effect of LY3884963 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04408625
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Olga Uspenskaya-Cadoz, MD, PhD
Address 0 0
Prevail Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Prevail Therapeutics
Address 0 0
Country 0 0
Phone 0 0
(917) 336-9310
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04408625