Evaluation of Safety of Contraloid Acetate in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease

NCT04711486 | Completed Phase 1 DMC

• 1 other identifier: ContraloidAD
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with mild cognitive impairment due to Alzheimer's disease (MCI due to AD) are at high risk to develop Alzheimer´s dementia. The therapeutic agent Contraloid has the potential to influence the chronic neurodegenerative process of AD. As Contraloid was so far only administered to healthy subjects, the rational of the proposed study is first to collect safety data in patients diagnosed with MCI due to AD, as the absorption, distribution, metabolism and excretion processes may be altered by disease, aging, comorbidities and concomitant drug therapies. Additionally, the design of a subsequent phase II study will be based on the data of this study. The results of the exploratory analyses will enable power calculations and the identification of the most useful and reliable biomarkers for the subsequent proof of concept phase II study.

Conditions

Mild Cognitive Impairment Due to Alzheimer's Disease

Outcome Measures

Primary Outcomes (3)

• Safety: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  Number of Adverse Events

  From baseline (day 1) to follow-up (day 56)

• Safety: Number of Participants with abnormal laboratory values (urinalysis, CBC, Quick, PTT, Creatinine, CK, CRP, ALT, AST)

  Laboratory values: urinalysis, CBC, Quick, PTT, Creatinine, CK, CRP, ALT, AST

  From baseline (day 1) to follow-up (day 56)

• Safety: Number of Participants with abnormal ECG values

  ECG

  From baseline (day 1) to follow-up (day 56)

Secondary Outcomes (3)

• Pharmacokinetics: Peak Plasma Concentration (Cmax)

  pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28

• Pharmacokinetics: The time at which Cmax is observed (Tmax)

  pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28

• Pharmacokinetics: Terminal elimination half-life (t1/2) in plasma

  pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28

Other Outcomes (5)

• Efficacy: Change of biomarkers in CSF

  Baseline to end of treatment (day 28) to follow-up (day 56)

• Efficacy: Change of biomarkers in plasma

  Baseline to end of treatment (day 28) to follow-up (day 56)

• Efficacy optional: Change of biomarkers in feces

  Baseline to end of treatment (day 28) to follow-up (day 56)

Study Arms (2)

Contraloid acetate

EXPERIMENTAL

300 mg Contraloid/participant administered orally (for 28 days) as a single daily dose. Other Name: PRI-002

Drug: Contraloid acetate

Placebo

PLACEBO COMPARATOR

300 mg Placebo (Microcrystalline cellulose)/participant administered orally (for 28 days) as a single daily dose.

Drug: Placebo

Interventions

Contraloid acetate DRUG

Oral administration of drug substance capsules

Also known as: PRI-002

Contraloid acetate

Placebo DRUG

Oral administration of placebo without any exipients.

Also known as: Microcrystalline cellulose

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with MCI due to AD according to DSM-V
• Age between 50 and 80 years (male and female)
• MMSE score 22-30
• Written informed consent (according AMG §40 (1) 3b)
• Level of Aβ-oligomers: mind. 1fM
• CSF according to diagnosis (p-tau \> 62 pg/ml, total CSF Aβ 1-42/1-40 ratio ≤ 0.055)
• months prior to screening stable medication
• Females without childbearing potential

You may not qualify if:

• History of seizures
• History of stroke or TIA
• Unstable medical, neurological or psychiatric condition
• Current treatment with one of the following substances:
• Typical antipsychotic or neuroleptic medication within 6 months of screening
• Anti-coagulation medications within 3 months of screening
• Chronic use of opiates or opioids (including long-acting opioid medication) within 3 months of screening
• Stimulant medications (amphetamine, methylphenidate preparations, or modafinil) within 1 month of screening and throughout the study
• Chronic use of benzodiazepines, barbiturates, or hypnotics from 3 months before screening
• Persons who are legally detained in an official institution
• Persons who may be dependent on the sponsor, the investigator or the trial site
• Persons without caregiver
• Participation in other clinical trials according to AMG (1 month before the time of this trial)
• Persons showing EEG abnormalities

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Berlin Institute of Health: collaborator
• Federal Agency for Disruptive Innovation - SPRIN-D: collaborator

Study Sites (1)

Charité University Medicine

Berlin, 10117, Germany

Location

Related Publications (1)

• Kutzsche J, Cosma NC, Kauselmann G, Fenski F, Bieniek C, Bujnicki T, Pils M, Bannach O, Willbold D, Peters O. Oral PRI-002 treatment in patients with MCI or mild AD: a randomized, double-blind phase 1b trial. Nat Commun. 2025 May 6;16(1):4180. doi: 10.1038/s41467-025-59295-z.

  PMID: 40324978 DERIVED

MeSH Terms

Interventions

microcrystalline cellulose

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: January 15, 2021
• Study Start: December 8, 2020
• Primary Completion: January 13, 2022
• Study Completion: January 13, 2022
• Last Updated: August 23, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)