NP001, Alzheimer's Disease, and Blood Markers of Inflammation

NCT03179501 | Terminated Phase 1 FDA Drug

• 1 other identifier: H039
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 placebo-controlled biomarker study of NP001 in individuals with Alzheimer's Disease.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Inflammatory monocyte-associated biomarkers

  The primary endpoint is changes from baseline at 1 and 7 days following dosing in percent monocyte expression levels of CD16 and HLA-DR.

  7 days

Secondary Outcomes (1)

• Adverse Events

  7 days

Study Arms (2)

NP001

EXPERIMENTAL

NP001

Drug: NP001

Placebo

PLACEBO COMPARATOR

Normal saline

Drug: Placebo

Interventions

NP001 DRUG

NP001

NP001

Placebo DRUG

Normal saline

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, 55 years of age or older,
• Diagnosis of probable Alzheimer's disease using the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's disease and Related Disorders Association criteria by Principal Investigator,
• Score 14 to 24 (inclusive) on the Mini-Mental Status Examination,
• Global Clinical Dementia Rating (CDR) Scale ≥ 0.5 or greater with CDR memory ≥ 0.5 or greater,
• Score ≤ 4 or lower on the Hachinski Ischemic Scale,
• Score ≤ 5 on the Geriatric Depression Scale (GDS),
• Current (stable dose for 4 weeks or longer) or past treatment with acetylcholinesterase inhibitors, memantine, or cognitive enhancers are allowed,
• Females must not be of childbearing potential (i.e., must be post-menopausal with cessation of menses for ≥ 12 months or have been surgically sterilized which includes hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or tubal ligation),
• Males must agree not to engage in sexual relations with a woman of childbearing potential without effective means of birth control during the study and for 30 days after study drug administration. Must also agree to refrain from sperm donation from receipt of study drug and for 90 days thereafter.
• Be capable of providing written informed consent using a form that has been approved by the IRB.
• Have veins suitable for intravenous administration of study drug or alternatively, have a venous access device.

You may not qualify if:

• Diagnosis of another neurologic disorder which can mimic Alzheimer's disease including dementia with Lewy Bodies, frontotemporal dementia and normal pressure hydrocephalus,
• Diagnosis of other neurologic disorders which can also impair cognition including stroke, MS, seizures, CNS tumors,
• Uncontrolled major psychiatric disorder,
• History of unstable medical illness in the 3 months prior to screening including emergent hospitalizations,
• Diagnosis of any of the following disorders: systemic sclerosis/scleroderma, inflammatory bowel disease, systemic lupus erythematosus (SLE), rheumatoid arthritis, mixed connective tissue disease, polymyalgia rheumatica, giant cell arteritis, polymyositis, dermatomyositis, and psoriasis,
• Active pulmonary disease under treatment including uncontrolled asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, pulmonary infection in the last 3 months, or history of aspiration,
• History of unexplained jaundice by subject report,
• History of Hepatitis A, B, or C or HIV by subject report,
• History of stem cell therapy,
• History of immune modulator therapy (e.g., corticosteroids, IV immunoglobulin, immunosuppressive chemotherapeutic agents, plasma exchange, GM-CSF, MCSF, interferons, infliximab, natalizumab, fingolimod \[GILENYA\], masitinib, ibudilast, tofacitinib citrate \[XELJANZ\], or any other approved drugs intended to affect the immune system) within 12 weeks of Screening Visit. Locally-acting corticosteroids (inhaled, intranasal, and topical) are permitted,
• Participation in an experimental drug trial (of agents other than immune modulators) within 12 weeks prior to Screening Visit. Observational trials with no intervention are acceptable provided permission from the other study sponsor is obtained in writing,
• Systolic blood pressure \< 100 mm Hg or \> 160 mm Hg, diastolic blood pressure \> 98 mm Hg. Patients on stable treatment for at least 3 months for hypertension are allowed as long as they meet entry criteria,
• Hematocrit \< 33%, platelet count \< lower limit of normal, or neutrophil count \< 1,500/mm3,
• Estimated creatinine clearance (eCCr) \< 50 mL/minute by Cockcroft-Gault Formula,
• Elevated aspartate aminotransferase (AST) or alanine aminotransferance (ALT) greater than 3 times the upper limit of normal,

Sponsors & Collaborators

• Beau Nakamoto: lead
• Neuraltus Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Hawaii Clinics at Kakaako

Honolulu, Hawaii, 96813, United States

Location

Related Publications (4)

• Miller RG, Block G, Katz JS, Barohn RJ, Gopalakrishnan V, Cudkowicz M, Zhang JR, McGrath MS, Ludington E, Appel SH, Azhir A; Phase 2 Trial NP001 Investigators. Randomized phase 2 trial of NP001-a novel immune regulator: Safety and early efficacy in ALS. Neurol Neuroimmunol Neuroinflamm. 2015 Apr 9;2(3):e100. doi: 10.1212/NXI.0000000000000100. eCollection 2015 Jun.

  PMID: 25884010 BACKGROUND

• Miller RG, Zhang R, Block G, Katz J, Barohn R, Kasarskis E, Forshew D, Gopalakrishnan V, McGrath MS. NP001 regulation of macrophage activation markers in ALS: a phase I clinical and biomarker study. Amyotroph Lateral Scler Frontotemporal Degener. 2014 Dec;15(7-8):601-9. doi: 10.3109/21678421.2014.951940. Epub 2014 Sep 5.

  PMID: 25192333 BACKGROUND

• Zhang R, Miller RG, Madison C, Jin X, Honrada R, Harris W, Katz J, Forshew DA, McGrath MS. Systemic immune system alterations in early stages of Alzheimer's disease. J Neuroimmunol. 2013 Mar 15;256(1-2):38-42. doi: 10.1016/j.jneuroim.2013.01.002. Epub 2013 Feb 4.

  PMID: 23380586 BACKGROUND

• Pey P, Pearce RK, Kalaitzakis ME, Griffin WS, Gentleman SM. Phenotypic profile of alternative activation marker CD163 is different in Alzheimer's and Parkinson's disease. Acta Neuropathol Commun. 2014 Feb 14;2:21. doi: 10.1186/2051-5960-2-21.

  PMID: 24528486 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Beau Nakamoto, MD PhD

  University of Hawaii

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa

Model Details: Single-site, randomized, double-blind, placebo-controlled

Study Record Dates

• First Submitted: June 5, 2017
• First Posted: June 7, 2017
• Study Start: September 1, 2017
• Primary Completion: July 31, 2018
• Study Completion: July 31, 2018
• Last Updated: October 22, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)