Randomised, double-blind, placebo-controlled study to assess safety and efficacy of PRI-002 in patients with MCI or mild dementia due to Alzheimer’s disease (AD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prinnovation GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

1 Dec 2023 → ongoing

Decision date (initial)

2023-10-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PRInnovation GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

Safety
To evaluate the safety and tolerability of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD, based on incidence of drug-related adverse events (AEs).

Efficacy
To evaluate the efficacy of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD, based on the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

Secondary objectives 4

1. To evaluate safety and tolerability of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD, based on AEs, amyloid related imaging abnormalities oedema (ARIA-E) and haemosiderin (ARIA-H), and treatment discontinuations due to AEs.
2. To evaluate clinical outcome measures and biomarkers of multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD.
3. To follow drug levels of PRI-002 during multiple doses of PRI-002 in subjects with MCI or mild dementia due to AD.
4. To evaluate the relationship between PRI‐002 exposure and efficacy and the relationship between PRI‐002 exposure and safety in subjects with MCI or mild dementia due to AD.

Conditions and MedDRA coding

Alzheimer's disease

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Signed and dated written informed consent obtained from the subject and study companion in accordance with applicable regulations
2. Male or female, aged 55 to 80 years, inclusive
3. For female subjects: not being of child-bearing potential
4. Body mass index (BMI) between 18.5 and 30.0 kg/m2, inclusive
5. Diagnosed with MCI due to AD or mild dementia due to AD, according to the National Institute on Aging and Alzheimer’s Association (NIA‐AA) criteria
6. MMSE score of 22 to 30, inclusive
7. Repeatable battery for the assessment of neuropsychological status - delayed memory index (RBANS-DMI) score ≤85
8. CDR global score of 0.5 or 1 with a memory score ≥0.5
9. Confirmation of AD diagnosis, by CSF biomarker profile reflecting AD, according to NIA-AA, or existing positive amyloid positron emission tomography (PET) evidence

Exclusion criteria 1

1. History or evidence of any other central nervous system (CNS) disorder(s) that could be interpreted as a cause of cognitive impairment or dementia

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of subjects with at least 1 drug-related AE or drug-related serious adverse event (SAE) between Baseline and Week 48
2. Change from Baseline to Week 48 in global outcome as measured by CDR-SB.

Secondary endpoints 11

1. Percentage of subjects with AEs and SAEs from Baseline until End of Study (EoS)
2. Percentage of subjects with ARIA-E and ARIA-H from Baseline until End of Treatment (EoT)
3. Percentage of subjects who stopped treatment due to AEs or SAEs from Baseline until EoT
4. Change from baseline to Week 48, of: • Alzheimer's disease cooperative study - activities of daily living inventory (ADCS-ADL) • Alzheimer disease assessment scale - cognitive subscale, 13 tests (ADAS-Cog 13)
5. Change from Baseline to EoT of: Cerebrospinal fluid (CSF) concentrations of AD‐related biomarkers including, but not limited to, ratio Aβ 1-42/1-40, p-tau, t-tau, Aβ oligomers, tau oligomers
6. Change from Baseline to EoT of: Plasma concentrations of AD-related biomarkers including, but not limited to, ratio Aβ 1-42/1-40, p-tau, t-tau, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and Aβ oligomers
7. PRI-002 plasma concentrations over time
8. Change from Baseline to EoT of: Mini mental state examination (MMSE) scores
9. Change from Baseline to EoT of: • CDR-SB • ADCS-ADL • ADAS-Cog 13
10. Change from Baseline to EoT of: Relationship between changes in CSF and plasma biomarkers and clinical changes (CDR‐SB, ADCS‐ADL, ADAS‐Cog 13, MMSE)
11. Relationships between PRI‐002 plasma concentrations and clinical changes (CDR‐SB, ADCS‐ADL, ADAS‐Cog 13, MMSE) and safety endpoints (AEs and SAEs)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prinnovation GmbH

Sponsor organisation

Prinnovation GmbH

Address

Merowingerplatz 1a, Bilk Bilk

City

Duesseldorf

Postcode

40225

Country

Germany

Scientific contact point

Organisation

Prinnovation GmbH

Contact name

Prof. Dr. Dieter Willbold

Public contact point

Organisation

Prinnovation GmbH

Contact name

Dr. Gerhard Tischler

Locations

7 EU/EEA countries · 45 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 116 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

20 submissions — initial application plus substantial / non-substantial modifications