MAD Phase I Study to Investigate Contraloid Acetate

• Status: Completed
• Trial end date: 2019-04-03
• Target enrollment: 0
• Participant gender: All

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.

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

Details

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

Criteria

Inclusion Criteria:

• 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)

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, female: 12,0 - 16,0 g/dL)

• CK level higher than 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.