SAD Phase I Study (First-in-human) to Investigate Contraloid Acetate
Condition: Alzheimer Dementia; Alzheimer Disease
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a single-center first-in-human single-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 not designed to reduce brain plaque load or total A-beta
      in cerebrospinal fluid. The study drug is blood-brain-barrier penetrable [1] and has
      demonstrated target engagement in vitro and in vivo [2, 3]. Preclinical 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.
    

Detailed description: 
      The investigation on the compound Contraloid acetate in a single-ascending-dose phase I study
      (first-in-human) has been performed in 40 healthy male participants, randomly assigned to the
      treatment. Main focus was on the evaluation of the outcome of the safety and tolerability;
      secondarily the pharmacokinetic characteristics of the compound were assessed. Five different
      ascending doses (4, 12, 36, 108, and 320 mg Contraloid) administered orally as a single dose,
      were tested in five cohorts on respectively six participants per cohort, additionally two
      participants of each cohort received placebo.

      In order to maintain the highest level of security for the participants of this
      first-in-human study a staggered design was used. First, only two sentinels of each cohort
      were administered with the study drug or placebo (ratio 1:1). Only after assessing all
      available data by the data safety and monitoring board (DSMB), the rest of the cohort (5
      study drug : 1 placebo) were allowed to be treated. This took place on two consecutive days,
      administering the study drug to three participants per each starting day. After DSMB
      permission the next higher dose level was started in the next cohort with the same scheme of
      administration.

      During the screening period the informed consent was obtained and the evaluation of the
      inclusion and exclusion criteria, collection of demographic data and previous medical
      history, physical examination and health assessment, 12-lead ECG were performed. Additionally
      vital signs, haemogram, coagulation, biochemistry and urine analysis determination, as well
      as serology and testing of drug abuse were carried out.

      On the first study day the participants received in fasting conditions the study drug after
      re-evaluation the inclusion/exclusion criteria. For monitoring the laboratory parameters and
      the pharmacokinetics of Contraloid blood draws were performed in a predetermined frequency.
      Physical conditions, vital signs, ECG and EEG, concomitant medication, adverse events were
      monitored closely. Sentinels stayed in the Phase-I Unit for 72 hours, and the remaining
      participants of the cohort for 24 hours. A follow-up was performed on Days 3, 4 and 8. The
      study was double-blinded and conducted under the EU regulations and Good Clinical Practice
      (GCP) and national Austrian law. Monitoring and PV was performed by the CRO NeuroScios, DM by
      Fundación Teófilo Hernando, Spain, bio-analytics by Triskelion, The Netherlands.

      Contraloid (alias RD2, alias PRI-002) is an 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 not designed to reduce brain plaque load or total A-beta in
      cerebrospinal fluid. The study drug is blood-brain-barrier penetrable [1] and has
      demonstrated target engagement in vitro and in vivo [2, 3]. Preclinical 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.
    

Intervention name(s): Contraloid
Intervention type(s): Drug
Intervention description(s): Oral administration of capsules, drug substance or placebo without any excipients.
Other intervention name(s): PRI-002
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Randomized, double-blind, placebo-controlled, multi-cohort trial.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
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