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

A Single-centre, Randomized, Placebo-controlled, Double-blind, Phase 1b Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Contraloid Acetate in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease

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.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment Due to Alzheimer's Disease
• Intervention / Treatment: Drug: Contraloid acetate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charité University Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients diagnosed with MCI due to AD according to DSM-V
2. Age between 50 and 80 years (male and female)
3. MMSE score 22-30
4. Written informed consent (according AMG §40 (1) 3b)
5. Level of Aβ-oligomers: mind. 1fM
6. CSF according to diagnosis (p-tau > 62 pg/ml, total CSF Aβ 1-42/1-40 ratio ≤ 0.055)
7. 3 months prior to screening stable medication
8. Females without childbearing potential

Exclusion Criteria:

1. History of seizures
2. History of stroke or TIA
3. Unstable medical, neurological or psychiatric condition

4. 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
5. Persons who are legally detained in an official institution
6. Persons who may be dependent on the sponsor, the investigator or the trial site
7. Persons without caregiver
8. Participation in other clinical trials according to AMG (1 month before the time of this trial)
9. Persons showing EEG abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Contraloid acetate; 300 mg Contraloid/participant administered orally (for 28 days) as a single daily dose. Other Name: PRI-002	Drug: Contraloid acetate; Oral administration of drug substance capsules; Other Names: PRI-002
PLACEBO_COMPARATOR: Placebo; 300 mg Placebo (Microcrystalline cellulose)/participant administered orally (for 28 days) as a single daily dose.	Drug: Placebo; Oral administration of placebo without any exipients.; Other Names: Microcrystalline cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Peak Plasma Concentration (Cmax)	Cmax in plasma	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)	Tmax in plasma	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	t1/2 in plasma	pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Change of biomarkers in CSF	Biomarkers: p-tau, t-tau, NFL, Aβ 1-40, Aβ 1-42 and Aβ and tau oligomers	Baseline to end of treatment (day 28) to follow-up (day 56)
Efficacy: Change of biomarkers in plasma	Biomarkers: p-tau, t-tau, NFL, Aβ 1-40, Aβ 1-42 and Aβ and tau oligomers	Baseline to end of treatment (day 28) to follow-up (day 56)
Efficacy optional: Change of biomarkers in feces	Biomarkers: p-tau, t-tau, NFL, Aβ 1-40, Aβ 1-42 and Aβ and tau oligomers	Baseline to end of treatment (day 28) to follow-up (day 56)
Efficacy: Change in CERAD+ test battery scores		Baseline to end of treatment (day 28) to follow-up (day 56)
Efficacy: Change in CDR-Sum of boxes		Baseline to end of treatment (day 28) to follow-up (day 56)

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Berlin Institute of Health; Federal Agency for Disruptive Innovation - SPRIN-D

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 8, 2020
• Primary Completion (ACTUAL): January 13, 2022
• Study Completion (ACTUAL): January 13, 2022

Study Registration Dates

• First Submitted: December 15, 2020
• First Submitted That Met QC Criteria: January 13, 2021
• First Posted (ACTUAL): January 15, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 23, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: ContraloidAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No