Nasal Protollin in Early Symptomatic Alzheimer's Disease

NCT07187141 | Completed Phase 1 FDA Drug

• 1 other identifier: 2021P000774
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

In this research study investigators aim to learn more about a new drug called Protollin as a possible new treatment for Alzheimer's Disease (AD). The primary goal is to assess the safety and tolerability.

Conditions

Alzheimer Disease (AD)

Keywords

Alzheimer's disease; Protollin; immune response

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of ascending doses of nasal Protollin

  Safety and tolerability of ascending doses of nasal Protollin following administration of two doses one week apart in subjects, 60-85 years inclusive with Early Symptomatic Alzheimer's Disease (29-20 MMSE classification). Safety will be assessed by physical examination (including evaluation of the nose and oropharynx), laboratory studies, EKG, and elicited and spontaneously reported signs and symptoms, using the FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007) for the evaluation of toxicities and reactogenicity. Tolerability will be assessed by the degree of severity of both spontaneously reported and elicited symptoms and associated signs, systemically and at the site of administration following administration of nasal Protollin, if thought by the investigator to be related or possibly related to its administration.

  Day 1 (enrollment) to 180 days (end of study)

Study Arms (4)

Cohort A

ACTIVE COMPARATOR

Protollin 0.1 mg or placebo

Drug: Protollin

Cohort B

ACTIVE COMPARATOR

Protollin 0.5 mg or placebo

Drug: Protollin

Cohort C

ACTIVE COMPARATOR

Protollin 1.0 mg or placebo

Drug: Protollin

Cohort D

ACTIVE COMPARATOR

Protollin 1.5 mg or placebo

Drug: Protollin

Interventions

Protollin DRUG

For the 0.1, 0.5, and 1.0 mg dose groups, Protollin (450 μL per vial) in an aqueous buffer will be administered in two, 0.1 μL sprays, one per nostril. For the 1.5 mg dose group, Protollin (450 muL per vial) in an aqueous buffer will be administered in three, 0.1 μL sprays, two in one nostril and one in the other nostril.

Cohort A; Cohort B; Cohort C; Cohort D

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The Sponsor will rely on NIA-AA Alzheimer's Disease Diagnostic Guidelines1 for Early Symptomatic Alzheimer's Disease and have a MMSE of 29-20.
• Age between 60-85 years (inclusive).
• Good general health with no disease expected to interfere with the study.
• On a stable medication regimen for 8 weeks prior to the study and which is anticipated to remain stable during the study.
• Subject is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile). ). If a woman is of childbearing potential, her partner is required to use contraception throughout the study (for those identifying as male).
• Ability to understand and provide informed consent.

You may not qualify if:

• Any significant neurologic disease including Parkinson's disease, multi-infarct dementia, Huntington's disease, frontotemporal dementia, Lewy body dementia, normal pressure hydrocephalus, brain tumor, brain hemorrhage with persistent neurologic deficits, progressive supra-nuclear palsy, seizure disorder, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
• Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease.
• History of autoimmune disease.
• Current treatment with immunomodulatory or immunosuppressive drugs, or corticosteroid administration by any route of administration (including nasal corticosteroids) within the past month.
• Major depression or bipolar disorder or a history of schizophrenia.
• History of alcohol or substance abuse or dependence within the past 2 years.
• History within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment.
• Clinically significant abnormalities (defined as greater than mild on the FDA's vaccine toxicity scale) in screening laboratories.
• Participation in another clinical trial of an investigational drug concurrently or within the past 30 days.
• Active COVID-19 disease
• Amyloid-negative PET scan (at screening)
• COVID-19 vaccine within past 10 days or any other vaccine within past 7 days (at dosing)

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• I-Mab Biopharma US Limited: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Protollin

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Neurologist

Model Details: This is a randomized, double-blind, Phase I, ascending dose study evaluating four dose cohorts.

Study Record Dates

• First Submitted: September 2, 2025
• First Posted: September 22, 2025
• Study Start: November 18, 2021
• Primary Completion: September 22, 2022
• Study Completion: February 21, 2023
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)