MAD Phase I Study to Investigate Contraloid Acetate

NCT03955380 | Completed Phase 1 DMC

• 1 other identifier: EUDRA-CT: 2018-002500-14
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center multiple-ascending-dose clinical trial assessing the safety and tolerability of oral dosing of Contraloid acetate in healthy volunteers. The study drug Contraloid (alias RD2, alias PRI-002) is an orally available all-D-peptide, which was developed to directly destroy toxic and replicating A-beta oligomer prions, by disassembling them into A-beta monomers. The study drug is specifically designed for the curative or at least disease-modifying treatment of cognition, memory and behavior deficits in Alzheimer´s disease patients. The study drug is BBB penetrable \[1\] and has demonstrated target engagement in vitro and in vivo \[2, 3\]. Treatments in three different transgenic mouse models in three different laboratories yielded improved cognition and deceleration of neurodegeneration, even under truly non-preventive treatment conditions and even when applied orally \[2-5\]. The hereby obtained PRI-002 plasma levels have also been achieved in humans after single oral dosing.

Conditions

Alzheimer Dementia; Alzheimer Disease

Keywords

anti-prionic; anti-Abeta-pionic; treatment of cognition and memory deficits; AD patients; AD stage-independent; NOT anti-amyloid; neuron specific Ca-ion reduction

Outcome Measures

Primary Outcomes (10)

• Assessment of safety and tolerability of Contraloid by monitoring vital signs, ECG and lab values

  To evaluate the safety and tolerability of Contraloid acetate in healthy subjects by assessing the number, severity and type of adverse events, including changes in vital signs, physical examinations, laboratory safety tests and ECGs.

  21 days for cohort 1 and 35 days for cohort 2

• Assessment of pharmacokinetics of Contraloid: Area under curve (AUC) in plasma

  Area under curve (AUC) in plasma

  168 hours

• Assessment of pharmacokinetics of Contraloid: Cmax in plasma

  Cmax in plasma

  21/35 days

• Assessment of pharmacokinetics of Contraloid: Tmax in plasma

  Tmax in plasma

  21/35 days

• Assessment of pharmacokinetics of Contraloid: Terminal elimination half-life (t1/2) in plasma

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

  21/35 days

• Assessment of pharmacokinetics of Contraloid: distributive half-life (t1/2alpha) in plasma

  distributive half-life (t1/2alpha) in plasma

  21/35 days

• Assessment of pharmacokinetics of Contraloid: terminal elimination half-life (t1/2beta) in plasma

  Terminal elimination half-life (t1/2beta) in plasma

  21/35 days

• Assessment of pharmacokinetics of Contraloid: Elimination Constant (Kel alpha) in plasma

  Elimination Constant (Kel alpha) in plasma

  21/35 days

• Assessment of pharmacokinetics of Contraloid: Elimination Constant (Kel beta) in plasma

  Elimination Constant (Kel beta) in plasma

  21/35 days

• AUC0-24 of Contraloid does not exceed of 2.3 µg·h/mL

  Additionally, the AUC0-24 values of Contraloid in plasma will be determined in order to ensure that the recommended AUC0-24 of Contraloid does not exceed of 2.3 µg·h/mL in any of the subjects.

  21/35 days

Study Arms (4)

Active Comparator: Contraloid 160 mg

ACTIVE COMPARATOR

160 mg Contraloid/participant administered orally (for 14 days in the first cohort and for 28 days in the second cohort) as a single daily dose.

Drug: Contraloid

Active Comparator: Contralod 320mg

ACTIVE COMPARATOR

320 mg Contraloid/participant administered orally (for 14 days in the first cohort and for 28 days in the second cohort) as a single daily dose.

Drug: Contraloid

Placebo Comparator (for Contraloid) 160 mg

PLACEBO COMPARATOR

160 mg placebo/participant administered orally (for 14 days in the first cohort and for 28 days in the second cohort) as a single daily dose.

Drug: Contraloid

Placebo Comparator (for Contraloid) 320 mg

PLACEBO COMPARATOR

320 mg placebo/participant administered orally (for 14 days in the first cohort and for 28 days in the second cohort) as a single daily dose.

Drug: Contraloid

Interventions

Contraloid DRUG

Oral administration of capsules, drug substance or placebo without any exipients.

Also known as: PRI-002

Active Comparator: Contralod 320mg; Active Comparator: Contraloid 160 mg; Placebo Comparator (for Contraloid) 160 mg; Placebo Comparator (for Contraloid) 320 mg

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects willing and able to give their written consent to participate in the trial after having received information about the study design, the objectives of the project, the possible derivative risks, and their right to withdraw from the study at any time and for any reason.
• Healthy male and female subjects aged within: 18 to 45 years (limits included).
• With clinical history and physical examination results within normality.
• Electrocardiogram without clinically significant pathologic abnormalities and with QTc values lesser than 450 ms.
• Normotensive as defined by Systolic Blood Pressure ≤ 150 mm Hg. Diastolic Blood Pressure ≤ 90 mm Hg.
• BMI between 19.0 and 30.0 kg/m2.
• Body weight between 55 and 85 kg, inclusive.
• Women who were neither pregnant (negative urine pregnancy test) nor nursing and who were either:
• Surgically sterile (bilateral tubal ligation, hysterectomy)

You may not qualify if:

• Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment that might increase the risk to the subject or confound the interpretation of safety observations.
• Evidence of active infection requiring antibiotic therapy within 14 days prior to screening.
• Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
• History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin.
• Seropositive for human immunodeficiency virus (HIV).
• History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for Hepatitis B surface antigen \[HbsAg\] or anti-Hepatitis C \[HCV\] antibody).
• Clinically significant abnormalities in screening laboratory tests, including:
• Absolute neutrophil count \< 1.4 x109
• Alanine transaminase (ALT) or aspartate transaminase (AST) \> 1.5 x the upper limit of normal (ULN)
• Absolute lymphocyte count \< 1.2 x 109
• Lactate dehydrogenase (LDH) \> 1.5 x ULN
• Total bilirubin level: Out of normal range 0-1.5 mg/dL
• eGFR \< 60 mL/min
• Hemoglobin (Hgb): out of normal range (male: 13,5-18,0 g/dL, female: 12,0 - 16,0 g/dL)
• CK level higher than 250U/L

Sponsors & Collaborators

• Prof. Dr. Dieter Willbold: lead
• Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany: collaborator
• Medical University of Vienna: collaborator
• NeuroScios, Austria: collaborator
• Nuvisan, Germany: collaborator
• Fundación Teófilo Hernando, Spain: collaborator
• Alzheimer's Association: collaborator

Study Sites (1)

Forschungszentrum Jülich

Jülich, 52425, Germany

Location

MeSH Terms

Conditions

Alzheimer Disease; Memory Disorders

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael Wolzt, MD

  University of Vienna, Austria

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Institute of Complex Systems, Structural Biochemistry (ICS-6)

Model Details: Randomized, double-blind, placebo-controlled, multiple ascending dose, multi-cohort

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 20, 2019
• Study Start: December 12, 2018
• Primary Completion: April 3, 2019
• Study Completion: April 3, 2019
• Last Updated: May 20, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)