Multiple Ascending Dose Study in Healthy Subjects

NCT03879278 | Terminated Phase 1 DMC

• 1 other identifier: NPT189-CL002
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This will be a Phase 1, randomized, double-blind, single center, placebo-controlled, multiple ascending dose (MAD) study in a maximum of 3 cohorts of 8 healthy male and female subjects each. Subjects in Cohorts 1, 2 and 3 will receive ascending multiple IV doses of NPT189 or matching placebo.

Conditions

Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Adverse event assessment in subjects receiving multiple intravenous infusions of NPT189

  Summary of the frequency and percentage of adverse events

  Day 1 through Day 112

Secondary Outcomes (6)

• Profile of pharmacokinetics (PK) of multiple intravenous (IV) infusions of NPT189 (Cmax)

  Day 1 through Day 112

• Profile of pharmacokinetics (PK) of multiple intravenous (IV) infusions of NPT189 (Tmax)

  Day 1 through Day 112

• Profile of pharmacokinetics (PK) of multiple (IV) infusions of NPT189 (AUC 0-tau)

  Day 1 through Day 112

• Profile of pharmacokinetics (PK) of multiple intravenous (IV) infusions of NPT189. Terminal elimination half-life (t 1/2)

  Day 1 through DAy 112

• Profile of pharmacokinetics (PK) of multiple (IV) infusions of NPT189. Clearance (CL)

  Day 1 through Day 112

Study Arms (3)

Treatment 2 mg/kg

OTHER

Five IV doses of 2 mg/kg NPT189 (n = 6) or matching placebo (n = 2) administered once per week

Drug: NPT189

Treatment 5 mg/kg

OTHER

Five IV doses of 5 mg/kg NPT189 (n = 6) or matching placebo (n = 2) administered once per week

Drug: NPT189

Treatment 12.5 mg/kg

OTHER

Five IV doses of 12.5 mg/kg NPT189 (n = 6) or matching placebo (n = 2) administered once per week

Drug: NPT189

Interventions

NPT189 DRUG

NPT189 is a recombinant immunoglobulin Fc fusion of GAIM (GAIM-IgG1Fc) as a potential treatment for peripheral amyloidosis.

Also known as: IgG1 (Immunoglobulin G), Fusion Protein, GAIM (General Amyloid Interaction Motif)

Treatment 12.5 mg/kg; Treatment 2 mg/kg; Treatment 5 mg/kg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years, inclusive, at screening
• Weight 45-120 kg, inclusive
• Body Mass Index of 18.0-32.0 kg/m2, inclusive
• Female subjects of childbearing potential (defined as not surgically sterile or at least 2 years postmenopausal confirmed by a Screening Follicular Stimulating Hormone level of \> 40) must agree to use two 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), IUD, complete abstinence, or vasectomized partner (6 months minimum) or male subjects who are sexually active with women of childbearing 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, electrocardiogram (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.

You may not qualify if:

• 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 , vitamin preparations and other food supplements, or herbal medications (e.g., St. John's Wort) 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 (the day before each dose administration only) or, drugs of abuse, or cotinine at Screening and on the day before each dose administration.
• Have clinically significant abnormalities in laboratory values as judged by the clinical investigator.
• Have a history of alcoholism and/or drug abuse.
• Unsuitable veins for infusion or blood sampling.

Sponsors & Collaborators

• Proclara Biosciences, Inc.: lead

Study Sites (1)

PRA Health Sciences

Groningen, 9728 NZ, Netherlands

Location

MeSH Terms

Conditions

Amyloidosis

Interventions

Immunoglobulin G

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Proclara Biosciences, Inc

  Proclara Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 18, 2019
• Study Start: March 6, 2019
• Primary Completion: June 27, 2019
• Study Completion: June 27, 2019
• Last Updated: August 19, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)