A Phase 1 Study to Assess the Safety of NLY01 in Healthy Subjects

NCT03672604 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: C-NRALY-PHAS1-M-0000
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, first-in-human study designed to assess the safety, tolerability, and pharmacokinetics of NLY01, a PEGylated form of exenatide, in healthy volunteers. NLY01 is being developed as a potential treatment for neurodegenerative disorders including Parkinson's disease. This study is intended to identify the appropriate dose-range for evaluation in Parkinson's disease patients.

Conditions

Safety and Tolerability in Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Treatment-Related Adverse Events

  Frequency and intensity of treatment-related adverse events as assessed using the CTCAE v4.03 criteria and the DMID Adult Toxicity Table for GI-related events.

  Day 1 through Day 29 (Part A) or Day 57 (Part B)

Secondary Outcomes (2)

• Pharmacokinetics of NLY01

  Periodic, predose through Day 29 (Part A) or Day 57 (Part B)

• Immunogenicity

  Periodic, predose through Day 29 (Part A) or Day 57 (Part B)

Study Arms (3)

Part A: Single Dose

PLACEBO COMPARATOR

Cohort 1 = 0.25 mg NLY01 Cohort 2 = 0.8 mg NLY01 Cohort 3 = 2.5 mg NLY01 Cohort 4 = 5 mg NLY01 Cohort 5 = 10 mg NLY01 All cohorts include 8 subjects randomized to receive a single dose of NLY01 or placebo (6 active, 2 placebo).

Drug: NLY01

Part B: Multiple Dose

PLACEBO COMPARATOR

In Part B, NLY01 or placebo will be administered once-weekly for 4 doses. There will be 3 sequentially-enrolled, ascending-dose cohorts of 8 subjects (6 active, 2 placebo). Doses in Part B will be a fraction of the maximum tolerated dose (MTD) established in Part A. Cohort 6 = 15% of the single-dose MTD Cohort 7 = 35% of the single-dose MTD Cohort 8 = 70% of the single-dose MTD

Drug: NLY01

Part C:Multiple Dose

PLACEBO COMPARATOR

In Part C, NLY01 or placebo will be administered once-weekly for 6 doses. Cohort 10 = 2.5 mg NLY01 Cohort 11 = 5 mg NLY01

Drug: NLY01

Interventions

NLY01 DRUG

NLY01, a PEGylated form of the anti-diabetic peptide exenatide

Also known as: Placebo, normal saline

Part A: Single Dose; Part B: Multiple Dose; Part C:Multiple Dose

Eligibility Criteria

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

You may qualify if:

• Men or women, 18 to 65 years of age, inclusive.
• BMI ≥ 18.5 and ≤ 32.0 kg/m2 at screening and check-in. BMI = weight (kg)/(height \[m\])2.
• Women of child-bearing potential must agree to use a medically acceptable method of contraception from screening through 30 days after the final dose of study drug.
• Non-childbearing potential.
• Men who are sexually active and whose partners are women of child-bearing potential must agree to use condoms from screening through 90 days after administration of study drug, and their partners must be willing to use a medically acceptable method of contraception (a barrier method, intrauterine device, or hormonal contraception) from screening through 90 days after administration of the last dose of study drug.
• Men must agree to not donate sperm from screening through 90 days after study drug administration.
• Subjects must be able to communicate effectively with the study personnel.
• Subjects must be healthy and without clinically significant abnormalities as assessed by review of medical and surgical history, physical examination, vital signs measurement, ECG, and laboratory evaluations conducted at screening and on Day -1 Check-in. A single repeat measurement/test may be performed to confirm vital signs, ECG, and clinical laboratory tests abnormalities (ie, to confirm that a subject is eligible).
• Subjects must be nonsmokers, defined as having abstained from tobacco- or nicotine containing products (eg, cigarettes, chewing tobacco, snuff, nicotine patches, and electronic cigarettes) in the 6 months prior to screening.
• Subjects must be informed of the nature and risks of the study and give written informed consent prior to screening.

You may not qualify if:

• Positive pregnancy test or is lactating/breastfeeding.
• History or presence of conditions which, in the judgment of the investigator, are known to interfere with the distribution, metabolism, or excretion of drugs.
• History or presence of conditions that may place the subject at increased risk as determined by the investigator.
• History of surgery or major trauma within 12 weeks of screening, or surgery planned during the study.
• History of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction within 12 months of screening.
• Use of prescription, OTC drugs (including herbal preparations) within 7 days or 5 half lives (if known), whichever is longer, prior to administration of the first dose of study drug.
• Has received a vaccination within 14 days prior to administration of the first dose of study drug.
• Has taken other investigational drugs or participated in any clinical study within 60 days or 5 half-lives (if known) of the investigational drug's PK, PD, or biological activity (if known), whichever is longer, prior to administration of the first dose of study drug in this study or is currently participating in another clinical study.
• Prior exposure to exenatide (Byetta® or Bydureon®).
• Significant blood loss (\> 450 mL) or has donated 1 or more units of blood or plasma within 6 weeks prior to study randomization.
• History of hypoglycemia.
• History of gastroparesis.
• History of pancreatitis.
• Positive urine results for drugs of abuse, alcohol, or cotinine screen.
• Positive screen for HIV-1 and HIV-2 antibodies, HBsAg, or HCV antibody.

Sponsors & Collaborators

• Neuraly, Inc.: lead

Study Sites (1)

ICON Early Phase Services/CRU

San Antonio, Texas, 78209, United States

Location

Related Publications (2)

• Yun SP, Kam TI, Panicker N, Kim S, Oh Y, Park JS, Kwon SH, Park YJ, Karuppagounder SS, Park H, Kim S, Oh N, Kim NA, Lee S, Brahmachari S, Mao X, Lee JH, Kumar M, An D, Kang SU, Lee Y, Lee KC, Na DH, Kim D, Lee SH, Roschke VV, Liddelow SA, Mari Z, Barres BA, Dawson VL, Lee S, Dawson TM, Ko HS. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease. Nat Med. 2018 Jul;24(7):931-938. doi: 10.1038/s41591-018-0051-5. Epub 2018 Jun 11.

  PMID: 29892066 BACKGROUND

• Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.

  PMID: 30957581 DERIVED

Related Links

• Neuraly, Inc website
• ICON Early Phase Services - Clinical Trial Site

MeSH Terms

Interventions

Saline Solution

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Emanuel DeNoia, MD

  ICON Early Phase Services/CRU

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: A Phase 1, first-in-human, double-blind, randomized, placebo-controlled, single-ascending followed by multiple-dose study

Study Record Dates

• First Submitted: September 13, 2018
• First Posted: September 14, 2018
• Study Start: September 19, 2018
• Primary Completion: July 30, 2019
• Study Completion: July 30, 2019
• Last Updated: September 30, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)