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

• ClinicalTrials.gov Identifier: NCT04711486
• Recruitment Status: Completed
• First Posted: January 15, 2021
• Last Update Posted: August 23, 2022
• Sponsor: Charite University, Berlin, Germany
• Collaborators: Berlin Institute of Health; Federal Agency for Disruptive Innovation - SPRIN-D
• Information provided by (Responsible Party): Oliver Peters, MD, Charite University, Berlin, Germany

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mild Cognitive Impairment Due to Alzheimer's Disease	Drug: Contraloid acetate; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 8, 2020
• Actual Primary Completion Date: January 13, 2022
• Actual Study Completion Date: January 13, 2022

Arms and Interventions

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 Name: 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 Name: Microcrystalline cellulose

Outcome Measures

Primary Outcome Measures :

1. Safety: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [ Time Frame: From baseline (day 1) to follow-up (day 56) ]
   Number of Adverse Events
2. Safety: Number of Participants with abnormal laboratory values (urinalysis, CBC, Quick, PTT, Creatinine, CK, CRP, ALT, AST) [ Time Frame: From baseline (day 1) to follow-up (day 56) ]
   Laboratory values: urinalysis, CBC, Quick, PTT, Creatinine, CK, CRP, ALT, AST
3. Safety: Number of Participants with abnormal ECG values [ Time Frame: From baseline (day 1) to follow-up (day 56) ]
   ECG

Secondary Outcome Measures :

1. Pharmacokinetics: Peak Plasma Concentration (Cmax) [ Time Frame: pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28 ]
   Cmax in plasma
2. Pharmacokinetics: The time at which Cmax is observed (Tmax) [ Time Frame: pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28 ]
   Tmax in plasma
3. Pharmacokinetics: Terminal elimination half-life (t1/2) in plasma [ Time Frame: pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28 ]
   t1/2 in plasma

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Germany

Charité University Medicine

Berlin, Germany, 10117

Sponsors and Collaborators

Charite University, Berlin, Germany

Berlin Institute of Health

Federal Agency for Disruptive Innovation - SPRIN-D

More Information

• Responsible Party: Oliver Peters, MD, Principal Investigator, Charite University, Berlin, Germany
• ClinicalTrials.gov Identifier: NCT04711486
• Other Study ID Numbers: ContraloidAD
• First Posted: January 15, 2021
• Last Update Posted: August 23, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alzheimer Disease; Cognitive Dysfunction; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders