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A Phase 1 Study to Assess the Safety of NLY01 in Healthy Subjects (NLY01-H1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03672604
Recruitment Status : Completed
First Posted : September 14, 2018
Last Update Posted : September 30, 2019
Sponsor:
Information provided by (Responsible Party):
Neuraly, Inc.

Tracking Information
First Submitted Date  ICMJE September 13, 2018
First Posted Date  ICMJE September 14, 2018
Last Update Posted Date September 30, 2019
Actual Study Start Date  ICMJE September 19, 2018
Actual Primary Completion Date July 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2018)
Treatment-Related Adverse Events [ Time Frame: Day 1 through Day 29 (Part A) or Day 57 (Part B) ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2018)
  • Pharmacokinetics of NLY01 [ Time Frame: Periodic, predose through Day 29 (Part A) or Day 57 (Part B) ]
    Serum concentration-time profiles for NLY01
  • Immunogenicity [ Time Frame: Periodic, predose through Day 29 (Part A) or Day 57 (Part B) ]
    Serum anti-drug antibody assessment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study to Assess the Safety of NLY01 in Healthy Subjects
Official Title  ICMJE A Phase 1, Single- and Multiple-Dose, Double-Blind, Randomized, Placebo-Controlled, Dose-Escalating Study to Assess the Safety, Tolerability, and Pharmacokinetics of NLY01 in Healthy Subjects
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.
Detailed Description

This is a Phase 1, first-in-human, double-blind, randomized, placebo-controlled, single and multiple-dose study to assess the safety, tolerability, and PK of NLY01, a PEGylated form of the anti-diabetic peptide exenatide, when administered by SC injection in healthy subjects.

In Part A of the study, 5 ascending-dose cohorts will be sequentially enrolled with an evaluation of safety and tolerability prior to each dose-escalation. Subjects in each cohort will be randomized to receive NLY01 or placebo. Each dose escalation and selection of doses for Part B will be conducted with oversight by an independently-chaired Safety Review Committee.

In Part B, subjects will receive once-weekly subcutaneous doses of NLY01 or placebo for 4 weeks. Three ascending-dose cohorts will be sequentially-enrolled with a safety review prior to each dose-escalation. Subjects in all Part B cohorts will receive fixed doses of NLY01 (or placebo) once-weekly for 4 weeks.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
A Phase 1, first-in-human, double-blind, randomized, placebo-controlled, single-ascending followed by multiple-dose study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Safety and Tolerability in Healthy Volunteers
Intervention  ICMJE Drug: NLY01
NLY01, a PEGylated form of the anti-diabetic peptide exenatide
Other Names:
  • Placebo
  • normal saline
Study Arms  ICMJE
  • Placebo Comparator: Part A: Single Dose

    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).

    Intervention: Drug: NLY01
  • Placebo Comparator: Part B: Multiple Dose

    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

    Intervention: Drug: NLY01
  • Placebo Comparator: Part C:Multiple Dose

    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

    Intervention: Drug: NLY01
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 26, 2019)
96
Original Estimated Enrollment  ICMJE
 (submitted: September 13, 2018)
64
Actual Study Completion Date  ICMJE July 30, 2019
Actual Primary Completion Date July 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Clinically significant cardiac changes demonstrated by ECG at screening or Day-1 including:

    • QTcF interval > 450 msec
    • PR interval ≤ 110 msec or > 240 msec
    • Evidence of second- or third-degree atrioventricular block
    • Pathological Q-waves (defined as Q-wave > 40 msec or depth greater than 0.5 mV)
    • Evidence of ventricular pre-excitation
    • Evidence of complete left BBB, incomplete left BBB, complete right BBB
    • Intraventricular conduction delay with QRS duration > 120 msec
    • Bradycardia (defined as sinus rate < 50 bpm) or tachycardia (defined as sinus rate > 100 bpm)
  • Has any of the following abnormal vital signs at screening or Day-1:

    • Pulse < 40 or > 100 bpm
    • Respiratory rate < 8 or > 20 breaths per minute
    • Systolic blood pressure < 95 or > 145 mmHg
    • Diastolic blood pressure < 45 or > 90 mmHg
  • Serum potassium, chloride, calcium, or sodium outside the normal reference range at screening
  • Hepatic transaminases (ALT or AST) > 100 IU/mL at screening.
  • Any hematology, chemistry, or urinalysis test results that are clinically significant.
  • Any other condition or prior therapy that, in the investigator's opinion, would make the subject unsuitable for the study, or unable or unwilling to comply with the study procedures.
  • Unwilling or unlikely to comply with the requirements of the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03672604
Other Study ID Numbers  ICMJE C-NRALY-PHAS1-M-0000
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: As a Phase 1 safety study, data will be limited to adverse events and PK. This data will be provided in summary form and/or with descriptive statistics. Individual listings are not expected to provide further insight.
Responsible Party Neuraly, Inc.
Study Sponsor  ICMJE Neuraly, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Emanuel DeNoia, MD ICON Early Phase Services/CRU
PRS Account Neuraly, Inc.
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP