A Study of NPT189 in Healthy Subjects

A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of NPT189 in Healthy Subjects

The purpose of the study is to evaluate the safety and tolerability of single dose of NPT189 in healthy volunteers. The study will also evaluate the pharmacokinetic characteristics of NPT189.

Study Overview

• Status: Completed
• Conditions: Amyloidosis
• Intervention / Treatment: Drug: Placebo; Drug: NPT189

Detailed Description

This study is a Phase1, randomized, double-blind, placebo-controlled, single dose, dose escalation safety and tolerability study of NPT189 in health subjects. Six dose cohorts are planned each with a maximum of 8 participants per cohort. Participants will receive NPT189 by intravenous (IV) or a matching placebo by intravenous infusion. Safety, tolerability, and pharmacokinetics will be assessed.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9728 NZ
    • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects between the ages of 18 and 65 years (inclusive);
• Has provided written informed consent to participate in the study;
• Weigh ≥ 45kg and ≤ 120kg with Body Mass Index of 18-32 inclusive;
• Subject Rescreening: This study does not permit the re-enrollment of a subject who has discontinued from the study as a pre-treatment failure without approval from the sponsor unless the reason they were not included was because the required number of subjects needed at the time of randomization had already been met. Rescreened subjects must continue to meet all inclusion and exclusion criteria. All screening procedures must be performed within 28 days of dose administration
• Female subjects of childbearing potential (defined as not surgically sterile or at least two years postmenopausal confirmed by a Screening Follicle Stimulating Hormone (FSH) level of > 40) must agree to use one of the following forms of contraception from 60 days prior through 90 days following the dose of Study Drug: hormonal (oral, transdermal, implant, or injection), barrier (condom, diaphragm with spermicide), intrauterine device (IUD), complete abstinence, or vasectomized partner (6 months minimum) or male subjects who are sexually active with women of child-bearing potential must agree to complete abstinence or to use a condom for 90 days following the dose of Study Drug;
• No clinically significant abnormal findings on physical examination, vital signs, ECG, or clinical laboratory evaluation during screening; and systolic blood pressure between 140 mm and 90 mm Hg and diastolic blood pressure between 90 mm and 45 mm Hg.
• Can understand and sign the informed consent document, can communicate with the investigator, and can understand and comply with the requirements of the protocol.

Exclusion Criteria:

• Have a past or present serious medical illness or other medical or social reason that in the opinion of the Principal Investigator, would jeopardize the safety of the subject or impact the validity of the study results;
• Participation in a clinical trial (other than a screening visit) within 60 days of study drug administration;
• Use of any over-the-counter or prescription medication within 14 days prior to the dose of Study Drug or during the study, with the exception of hormonal contraceptives for women of childbearing potential, unless approved by the Principal Investigator or use of beta-blockers within 30 days prior to dose of Study Drug or during the study;
• Donation of blood or plasma within 30 days of the dose of Study Drug and throughout the duration of the study and for male subjects, donation of sperm through the duration of the study;
• Women who are nursing, pregnant, suspected of being pregnant, or trying to become pregnant, or are lactating, have a positive serum pregnancy test at screening or urine pregnancy test prior to administration of Study Drug regardless of childbearing potential;
• Positive blood screen for HIV, hepatitis B surface antigen (HbSAg), or hepatitis C as Screening, or a positive urine screen for alcohol (Day -1 only) or, drugs of abuse, or cotinine at Screening and on Day -1;
• Have clinically significant abnormalities in laboratory values as judged by the clinical investigator;
• Have a history of alcoholism and/or drug abuse;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator; Placebo	Drug: Placebo; Placebo
Experimental: Experimental; NPT189	Drug: NPT189; IgG1 Fc-GAIM fusion protein, a recombinant fusion protein; Other Names: IgG1 (Immunoglobulin G); Fusion Protein; GAIM (General Amyloid Interaction Motif)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of a single intravenous (IV) infusion of NPT189 (subjects experiencing adverse events)	Summary of the frequency and percentage of	Day 1 through to Day 49

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Profile of pharmacokinetics (PK) of a single intravenous (IV) infusion of NPT189 (Cmax)	Observed maximum concentration (Cmax)	Day 1 through to Day 49
Profile of pharmacokinetics (PK) of a single intravenous (IV) infusion of NPT189 (Tmax)	Time of the maximum measured concentration (Tmax)	Day 1 through to Day 49
Profile of pharmacokinetics (PK) of a single intravenous (IV) infusion of NPT189 (AUClast)	Area under the concentration-time curve from time zero to the last quantifiable concentration time-point (AUClast)	Day 1 through to Day 49
Profile of pharmacokinetics (PK) of a single intravenous (IV) infusion of NPT189 (AUCinf)	Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf)	Day 1 through to Day 49
Profile of pharmacokinetics (PK) of a single intravenous (IV) infusion of NPT189. Terminal elimination half-life (t 1/2)	Terminal elimination half-life (t 1/2)	Day 1 through to Day 49
Profile of pharmacokinetics (PK) of a single intravenous (IV) infusion of NPT189. Clearance (CL)	Clearance (CL)	Day 1 through to Day 49
Profile of pharmacokinetics (PK) of a single intravenous (IV) infusion of NPT189. Volume of distribution (Vd)	Apparent volume of distribution (Vd)	Day 1 through to Day 49

Collaborators and Investigators

• Sponsor: Proclara Biosciences, Inc.
• Investigators: Study Director: Proclara Biosciences, Proclara

Publications and helpful links

General Publications

• Krishnan R, Tsubery H, Proschitsky MY, Asp E, Lulu M, Gilead S, Gartner M, Waltho JP, Davis PJ, Hounslow AM, Kirschner DA, Inouye H, Myszka DG, Wright J, Solomon B, Fisher RA. A bacteriophage capsid protein provides a general amyloid interaction motif (GAIM) that binds and remodels misfolded protein assemblies. J Mol Biol. 2014 Jun 26;426(13):2500-19. doi: 10.1016/j.jmb.2014.04.015. Epub 2014 Apr 22.

Helpful Links

• Proschitsky, M et al., GAIM Fusions are Therapeutic Candidates for Peripheral Amyloidosis (2018).

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2018
• Primary Completion (Actual): February 17, 2019
• Study Completion (Actual): February 17, 2019

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Actual): August 15, 2019
• Last Update Submitted That Met QC Criteria: August 14, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins; Immunoglobulin G
• Other Study ID Numbers: NPT189-CL001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No