Phase1a, Dose-escalation Study of NNI-362 in Healthy Aged Volunteers

NCT ID: NCT04074837

Last Updated: 2023-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2021-08-15

Brief Summary

The purpose of this study is to examine the safety, tolerability and pharmacokinetics of single and multiple doses of NNI-362 in healthy aged population.

Detailed Description

The early clinical development strategy consists of the initial evaluation of safety and tolerability of NNI-362. This FIH Phase I includes single and multiple ascending dose studies in healthy aged volunteers. Assessment of suicidal ideation/behavior will be performed at baseline and at all study visits and on days of inpatient confinement in conformance with FDA recommendations.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo liquid suspension.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo liquid suspension

NNI-362, 10 mg

NNI-362 at 10 mg in liquid suspension

Group Type: ACTIVE_COMPARATOR

NNI-362

Intervention Type: DRUG

NNI-362 small molecule in liquid suspension.

NNI-362, 20 mg

NNI-362 at 20 mg in liquid suspension

Group Type: ACTIVE_COMPARATOR

NNI-362

Intervention Type: DRUG

NNI-362 small molecule in liquid suspension.

NNI-362, 60 mg

NNI-362 at 60 mg in liquid suspension

Group Type: ACTIVE_COMPARATOR

NNI-362

Intervention Type: DRUG

NNI-362 small molecule in liquid suspension.

NNI-362, 120 mg

NNI-362 at 120 mg in liquid suspension

Group Type: ACTIVE_COMPARATOR

NNI-362

Intervention Type: DRUG

NNI-362 small molecule in liquid suspension.

NNI-362, 240 mg

NNI-362 at 240 mg in liquid suspension

Group Type: ACTIVE_COMPARATOR

NNI-362

Intervention Type: DRUG

NNI-362 small molecule in liquid suspension.

Interventions

NNI-362

NNI-362 small molecule in liquid suspension.

Intervention Type: DRUG

Placebo

Placebo liquid suspension

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy aged volunteers of either sex between the ages of 50 and 72 inclusive at time of screening.

• Subjects must be in reasonably good health as determined by investigator based on medical history, vital signs measurements, physical examination, screening laboratory results and ECG.
• Normal age-related findings as well as well-controlled, chronic and stable medical conditions (e.g., hypertension, osteoarthritis, non-insulin dependent diabetes mellitus, osteoporosis, gout, Paget's disease, hypothyroidism) will not be exclusionary if they are not expected to compromise subject safety, study conduct, or study objectives.
• Non-interacting medications for stable allowable medical conditions will be allowed following review and approval by the medical monitor.
• An adequate understanding of the requirements of the study, provision of written informed consent, and agreement to abide by the study restrictions.
• Negative urine screen for drugs of abuse within 24 h before the administration of the first dose of study drug and in the multiple dose study upon readmission to the clinical unit from outpatient status.
• Body Mass Index (BMI) of between 18 and 30 kg/m2 inclusive, and a total body weight greater than 48kg at screening.

Exclusion Criteria

• • Women of child-bearing potential, defined as premenopausal (unless the potential research subject has previously undergone hysterectomy and/or bilateral salpingo-oophorectomy)

• Pregnant or breastfeeding
• Any clinically significant hematology, chemistry, coagulation, or urinalysis value at screening and day -1 Abnormal liver enzymes (ALT and/or AST >1.5X ULN) at screening and day -1
• Serum creatinine > ULN at screening and day -1
• Hemoglobin <13 g/dL for males or <11.5 g/dL for females, leukocytes <3.0 X 103/uL, absolute neutrophil count <1000/uL, or platelets <150 X 103/uL at screening and day -1
• Any significant medical illness that could compromise the interpretability of study data or affect subject safety including, but not necessarily limited to:

• Chronic pulmonary disease or sleep apnea
• Clinically significant cardiac arrhythmia (either at screening or based on history)
• Congestive heart failure, valvular heart disease or ischemic heart disease
• Pulmonary hypertension
• Any disorder of the kidney or urinary tract
• Active peptic ulcer disease, gastrointestinal bleeding, inflammatory bowel disease, chronic pancreatitis
• Liver disease (excluding Gilbert's syndrome)
• Any neurologic disorder other than chronic Bell's Palsy
• History of malignancy that has not been cured or in complete remission for at least 10 years (excluding resected non-metastatic basal cell carcinoma)
• History of seizure activity other than early childhood
• Any traumatic brain injury in adulthood
• Current smoker or nicotine user (quit less than 2 months)
• Active substance abuse.
• Glomerular filtration rate <50 mL/min based on Cockcroft-Gault calculation using ideal (lean) body weight or present weight.
• Difficulty swallowing

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 72 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Neuronascent, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Parexel, International

Glendale, California, United States

Countries

United States

References

Kelleher-Andersson J, Yoon E, Green C, McFarlane C, Bagheri D, Thomas LP, Turner RS. First-in-human study of neuron regenerative therapy NNI-362 to evaluate the safety, pharmacokinetics, and pharmacodynamics in healthy aged population. Alzheimers Res Ther. 2025 Aug 7;17(1):185. doi: 10.1186/s13195-025-01837-0.

Reference Type: DERIVED

PMID: 40775373 (View on PubMed)

Sumien N, Wells MS, Sidhu A, Wong JM, Forster MJ, Zheng QX, Kelleher-Andersson JA. Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease. Stem Cell Res Ther. 2021 Jan 13;12(1):59. doi: 10.1186/s13287-020-02126-3.

Reference Type: DERIVED

PMID: 33436007 (View on PubMed)

Other Identifiers

1R01AG056561-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NNI-001

Identifier Type: -

Identifier Source: org_study_id