Clinical trial NCT03179501: NP001, Alzheimer's Disease, and Blood Markers of Inflammation
Official title: Effect of Single Dose NP001 on Blood Markers of Inflammation in Individuals With Mild-to-Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: University of Hawaii
Sponsor class: OTHER
Collaborators: name: Neuraltus Pharmaceuticals, Inc.
First posted: 2017-06-07
Enrollment: 4
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-site, randomized, double-blind, placebo-controlled
Primary purpose: BASIC_SCIENCE

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

Detailed description: Abnormal inflammatory monocytes/macrophages, systemically and locally in the central nervous system (CNS), are implicated in the neuro-inflammatory process seen in Alzheimer's disease. NP001 is a novel immune regulator of inflammatory monocytes/macrophages.

Given the key role inflammatory monocytes/macrophages may play in the pathogenesis of AD, this study will assess the changes in inflammatory monocyte-associated biomarkers, including CD16 and HLA-DR, pre- and post- NP001.

This is a Phase 1 single-site, randomized, double-blind, placebo-controlled pilot biomarker study of a single dose of NP001 in individuals with mild-to-moderate Alzheimer's disease. Fourteen individuals will be enrolled and randomized 1:1 to NP001 and placebo. Drug or placebo will be given intravenously. Biomarkers will be measured at baseline and 1 and 7 days following infusion.

Eligibility criteria: Inclusion Criteria:

1. Male or female, 55 years of age or older,
2. 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,
3. Score 14 to 24 (inclusive) on the Mini-Mental Status Examination,
4. Global Clinical Dementia Rating (CDR) Scale ≥ 0.5 or greater with CDR memory ≥ 0.5 or greater,
5. Score ≤ 4 or lower on the Hachinski Ischemic Scale,
6. Score ≤ 5 on the Geriatric Depression Scale (GDS),
7. Current (stable dose for 4 weeks or longer) or past treatment with acetylcholinesterase inhibitors, memantine, or cognitive enhancers are allowed,
8. 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),
9. 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.
10. Be capable of providing written informed consent using a form that has been approved by the IRB.
11. Have veins suitable for intravenous administration of study drug or alternatively, have a venous access device.

Exclusion Criteria:

1. Diagnosis of another neurologic disorder which can mimic Alzheimer's disease including dementia with Lewy Bodies, frontotemporal dementia and normal pressure hydrocephalus,
2. Diagnosis of other neurologic disorders which can also impair cognition including stroke, MS, seizures, CNS tumors,
3. Uncontrolled major psychiatric disorder,
4. History of unstable medical illness in the 3 months prior to screening including emergent hospitalizations,
5. 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,
6. 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,
7. History of unexplained jaundice by subject report,
8. History of Hepatitis A, B, or C or HIV by subject report,
9. History of stem cell therapy,
10. 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,
11. 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,
12. 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,
13. Hematocrit \< 33%, platelet count \< lower limit of normal, or neutrophil count \< 1,500/mm3,
14. Estimated creatinine clearance (eCCr) \< 50 mL/minute by Cockcroft-Gault Formula,
15. Elevated aspartate aminotransferase (AST) or alanine aminotransferance (ALT) greater than 3 times the upper limit of normal,
16. Pregnant or lactating females,
17. Have any condition which, in the opinion of the investigator, would put the subject at risk by participating in this study.

Primary outcomes:
measure: Inflammatory monocyte-associated biomarkers
timeFrame: 7 days
Secondary outcomes:
measure: Adverse Events
timeFrame: 7 days
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: University of Hawaii Clinics at Kakaako
state: Hawaii
Study officials:
affiliation: University of Hawaii
name: Beau Nakamoto, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.