MAD Phase I Study 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 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.
    

Detailed description: 
      The investigation on the compound Contraloid acetate in a multiple-ascending-dose phase I
      study has been performed in 24 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. Two different ascending
      doses (160 and 320 mg Contraloid) administered orally (for 14 days in the first cohort and
      for 28 days in the second cohort) as a single daily dose, were tested in two cohorts on
      respectively eight participants per cohort, additionally four participants of each cohort
      received placebo.

      In order to maintain the highest level of security for the participants of this study a
      staggered design was used. First, only four sentinels of each cohort were administered with
      the study drug or placebo (ratio 2:2). Only after assessing all available data by the data
      safety and monitoring board (DSMB), the rest of the cohort (6 study drug: 2 placebo) were
      allowed to be treated. This took place on two consecutive days, administering the study drug
      to four participants per each starting day. After DSMB permission the next dose level was
      started 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, concomitant medication, adverse events were monitored
      closely. Sentinels stayed in the Phase-I Unit for 7 days, and the remaining participants of
      the cohort for 24 hours. The participants returned daily for administration. On Day 14/28
      (cohort 1/cohort 2) the participants were admitted to the phase 1 unit for another 24 h for
      PK-sampling. A follow-up was performed on Days 16/30, 17/31 and the End of Study Visit on Day
      21/35. 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 Fundacion Teofilo Hernando, Spain, Bioanalytics by Nuvisan, Germany.It is a
      Part the Cloud Translational Research Funding award from the Alzheimer´s Association.

      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 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.
    

Intervention name(s): Contraloid
Intervention type(s): Drug
Intervention description(s): Oral administration of capsules, drug substance or placebo without any exipients.
Other intervention name(s): PRI-002
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Randomized, double-blind, placebo-controlled, multiple ascending dose, multi-cohort
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