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CompletedNCT03298672Updated Sep 10, 2019

Safety, Tolerability, and Pharmacokinetics Study of NDX-1017

A Phase 1 interventional study of NDX-1017 and Placebo in Alzheimer Disease, sponsored by Athira Pharma. Completed at 1 site in United States. Open to participants aged 18 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-09-10.

Sponsored by Athira Pharma · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
88
Allocation
Randomized
Ages
18 Years to 85 Years
Sex
All
01

Study summary

This Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of NDX-1017 in healthy young and elderly subjects, and elderly subjects with amnestic mild cognitive impairment (MCI), Alzheimer's disease (mild, mild-to-moderate, or moderate), or mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or moderate).

Read the detailed description

NDX-1017 is being developed for the treatment of Alzheimer's disease (AD).

This Phase 1 randomized, placebo-controlled, double-blinded, first-in-human study will evaluate safety, tolerability, and pharmacokinetics of single and multiple ascending doses of NDX-1017 in healthy young and elderly subjects, and elderly subjects with mild AD. The study contains the following two parts:

Part A:

A single-ascending dose (SAD) study conducted in an inpatient setting for 3 days in healthy young male and healthy elderly male and female volunteers evaluated in up to 7 dose cohorts to identify the maximum tolerated dose (MTD) within the single dose range studied. Up to 56 subjects (aged 18 to 45 years for young and 60 to 85 years for elderly) may be enrolled in Part A.

Part B:

A multiple ascending dose (MAD) study conducted in an inpatient setting for 10 days in male or female healthy elderly volunteers (aged 60 to 85 years) or subjects with amnestic mild cognitive impairment (MCI), Alzheimer's disease (mild, mild-to-moderate, or moderate), or mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or moderate) (aged 40 to 85 years) in up to 6 dose cohorts that were proven tolerable in the SAD part of the study to identify the MTD within the multiple dose range studied. Up to 44 subjects (aged 40 to 85 years) may be enrolled in Part B.

Subjects will be screened for eligibility within 28 days (or 90 days for amnestic MCI, Alzheimer's Disease, or mixed dementia with Alzheimer's and vascular components) prior to enrollment. Those eligible will be admitted to an inpatient facility for investigational product administration, safety monitoring, and collection of blood or urine for pharmacokinetic evaluations.

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Conditions studied

  • Alzheimer Disease

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Keywords

  • Alzheimer's Disease
  • Dementia
  • Brain Diseases
  • Central Nervous System Diseases
  • Cognition
  • Neurodegenerative Diseases
  • Neurocognitive Disorders
  • Mental Disorders
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Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Generally in good health
  • Body mass index (BMI) of ≥ 18.0 and ≤ 30.0 kg/m2 at Screening, with minimum weight of 60 kg. (No BMI upper limit for mild AD and amnestic MCI subjects)
  • Male subjects and their partners must be willing to comply with the contraceptive requirements of the study. Only female subjects of non-childbearing potential are eligible for participation.
  • [Young subjects] Male subjects must be aged 18 to 45 years (inclusive) at the time of Screening.
  • [Healthy elder subjects only] Male and female subjects must be aged 60 to 85 years at the time of screening
  • [Amnestic MCI and Alzheimer's Subjects] 9. Patients with Alzheimer's disease, with confirmed diagnosis of amnestic mild cognitive impairment, Alzheimer's disease (mild, mild-to-moderate, or moderate), or mixed dementia with Alzheimer's and vascular components (mild, mild-to-moderate, or moderate).

    1. Either newly diagnosed treatment naïve patients, OR,
    2. Patients who are currently on standard Alzheimer's Disease treatment may be considered for participation if they are not tolerating treatment and/or they are willing and clinically able to tolerate a discontinuation, 14 days for dose titration + 5x half-lives for washout, or 4 weeks (whichever is longer) prior to randomization. For these patients, the screening window will be allowed for up to 90 days prior to randomization to evaluate discontinuation of symptomatic treatment for Alzheimer's disease.

Exclusion criteria

EXCLUSION CRITERIA:

  • Any medical condition that requires chronic medication use.
  • History of drug and/or alcohol abuse within 12 months prior to Screening.
  • History of having taken another investigational drug within 30 days prior to Admission (Day -1).
  • Donation of blood or plasma within 30 days prior to dosing.
  • Major surgery within 90 days prior to Admission (Day -1) or anticipated surgery during the study.
  • Smokers
  • [Healthy elderly subjects] Reported changes in cognition and reported history of declines in everyday life in the last year.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
88 participants (actual)

Study arms

  • Experimental
    NDX-1017

    NDX-1017 will be administered via subcutaneous injection

    Drug: NDX-1017

  • Placebo comparator
    Placebo

    Placebo will be administered via subcutaneous injection

    Drug: Placebo

Interventions

  • DrugNDX-1017

    Solution of NDX-1017 for subcutaneous injection

  • DrugPlacebo

    Placebo solution for subcutaneous injection

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What researchers measure

Primary outcomes

  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].

    Safety and tolerability of single or multiple ascending doses of NDX-1017 as measured by vital signs and clinical laboratory measurements.

    Time frame: Up to 20 days

Secondary outcomes

  1. Maximum observed plasma concentration (Cmax).

    Cmax will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.

    Time frame: Samples collected at predetermined timepoints within 48 hours post-dose.

  2. Time to maximum observed plasma concentration (Tmax).

    Tmax will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.

    Time frame: Samples collected at predetermined timepoints within 48 hours post-dose.

  3. Plasma concentration at the end of the dosing interval (Ctrough).

    Ctrough will be determined from the last plasma sample prior to the following dose (MAD only).

    Time frame: Samples collected at predetermined timepoints within 48 hours post-dose.

  4. Area under the plasma concentration time curve (AUC).

    AUC will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.

    Time frame: Samples collected at predetermined timepoints within 48 hours post-dose.

  5. Half-life (t1/2).

    t1/2 will be determined from all collected plasma samples from baseline through up to 48 hours post-dose.

    Time frame: Samples collected at predetermined timepoints within 48 hours post-dose.

06

Study locations

1 site
  • Biotrial Inc.
    Newark, New Jersey 07103, United States
07

References and documents

Publications

  • Hua X, Church K, Walker W, L'Hostis P, Viardot G, Danjou P, Hendrix S, Moebius HJ. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Positive Modulator of HGF/MET, Fosgonimeton, in Healthy Volunteers and Subjects with Alzheimer's Disease: Randomized, Placebo-Controlled, Double-Blind, Phase I Clinical Trial. J Alzheimers Dis. 2022;86(3):1399-1413. doi: 10.3233/JAD-215511. PubMed 35180125 ↗

Individual participant data

Plan to share: No

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Registry details

Key details

Study ID
NCT03298672
Lead sponsor
Athira Pharma
Collaborators
Alzheimer's Drug Discovery Foundation, Biotrial Inc.
Responsible party
Sponsor
First posted
Oct 2, 2017
Start date
Oct 9, 2017
Primary completion
Sep 5, 2019
Completion
Sep 5, 2019
Last update
Sep 10, 2019

Study contacts

Xue Hua, PhD
study director · Athira Pharma, Inc.

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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