SAD Phase I Study (First-in-human) to Investigate Contraloid Acetate

• Status: Completed
• Trial end date: 2018-07-27
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Prof. Dr. Dieter Willbold
• Collaborators: Fundación Teófilo Hernando, Spain; Helmholtz-Gemeinschaft Deutscher Forschungszentren, Germany; Medical University of Vienna; NeuroScios, Austria; Triskelion, The Netherlands

Criteria

Inclusion Criteria:

• 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

• Signed ICF

Exclusion Criteria:

• 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)

• CK level higher than normal values (250U/L)

• All prescription, over-the-counter and herbal medications are prohibited within 10 days prior to study dosing (with exception of calcium/vitamin D supplements, nasal steroids, ocular medications, and paracetamol ≤1000 mg/day at the discretion of the Investigator).

• Use of an investigational drug within 2 months prior to dosing in this study.

• Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs (e.g. small bowel disease, Crohn's disease, celiac disease, or liver disease.)

• Psychiatric history of current or past psychosis, bi-polar disorder, clinical depression, or anxiety disorder requiring chronic medication within the past 5 years.

• History of substance abuse, including alcohol

• Smokers

• History of substance or drug dependence, or positive urine drug screen at screening visit.

• History of head injury.

• Chronic kidney disease (defined as the presence of any degree of proteinuria on urine analysis and/or an eGFR of <60 ml/min using the MDRD formula).

• Any reason or opinion of the investigator that would prevent the subject from participation in the study.

• Inability to follow the instructions or an unwillingness to collaborate during the study.