Alzheimer Disease (AD)Phase 1NCT07187141
Nasal Protollin in Early Symptomatic Alzheimer's Disease
A Phase 1 study testing Protollin in people with Alzheimer Disease (AD), run by Brigham and Women's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Alzheimer Disease (AD)
- What is being tested?
- Protollin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Nov 2021to 21 Feb 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- Amyloid-positive PET scan (if subject meets all other inclusion criteria).
- Ability to understand and provide informed consent.
Who cannot join
- 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.
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- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Phase I Study of the Safety, Tolerability, and Immune Effects of Nasal Protollin in Subjects With Early Symptomatic Alzheimer's Disease
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.
Read the detailed description
In this research study investigators want to learn more about a new drug called nasal Protollin as a possible new treatment for Alzheimer's Disease (AD). In AD, there is accumulation in the brain of a toxic substance called amyloid. It is believed that this toxic substance causes brain cells to progressively waste away (degenerate) and die, causing a continuous decline in thinking, behavioral and social skills. Why amyloid accumulates is not completely understood.
The aim of this treatment is to remove toxic amyloid from the brain and prevent further degeneration. Although nasal Protollin has been given as part of vaccination programs, this is the first time Protollin will be given nasally (through the nose) in AD patients. Investigators aim to see if this way of giving the Protollin is safe and whether it stimulates the body's white blood cells to remove toxic amyloid from the brain and ultimately improve cognition. This will be a dose escalating (gradually increasing the dose in different subjects) study, which means we want to find the highest dose of Protollin that is safe to take. Protollin is not approved by the U.S. Food and Drug Administration (FDA). This means that Protollin can only be used in research studies.
This research study will compare Protollin to placebo. The placebo looks exactly like Protollin, but it does not contain any Protollin. During this study participants may get a placebo instead of Protollin. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons.
- Conditions
- Alzheimer Disease (AD)
- Being tested
- Protollin
- Keywords
- Alzheimer's disease, Protollin, immune response
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProtollinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Active comparator | Protollin 0.1 mg or placebo Receives: Drug: Protollin |
| Cohort B | Active comparator | Protollin 0.5 mg or placebo Receives: Drug: Protollin |
| Cohort C | Active comparator | Protollin 1.0 mg or placebo Receives: Drug: Protollin |
| Cohort D | Active comparator | Protollin 1.5 mg or placebo Receives: Drug: Protollin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 (enrollment) to 180 days (end of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2025
- Study start18 Nov 2021
- Primary completion22 Sep 2022
- Study completion21 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer Disease (AD)Studies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized, double-blind, Phase I, ascending dose study evaluating four dose cohorts.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- I-Mab Biopharma US Limited
- Responsible party
- Principal investigator, Tanuja Chitnis, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07187141
- Sponsor's protocol ID
- 2021P000774
- Status last verified
- Sep 2025
- First submitted
- 2 Sep 2025
- Last updated
- 22 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kolypetri P, da Silva P, Francisco RS Jr, Frenkel D, Cecere RR, Kiliaan PCJ, Montini F, Saxena S, Clementi WA, Liu X, Sun C, Bergmark RW, Singhal T, Saraceno TJ, Zimmermann J, Gale SA, Selkoe DJ, Chitnis T, Weiner HL. Nasal administration of Protollin enhances monocyte phagocytosis and decreases CD8+ T cell cytotoxicity in subjects with early Alzheimer's disease: a Phase 1 clinical trial. NPJ Aging. 2026 Jun 5. doi: 10.1038/s41514-026-00397-3. Online ahead of print.
PubMed 42248874
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of the Safety, Tolerability, and Immune Effects of Nasal Protollin in Subjects With Early Symptomatic Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT07187141
- Acronym / sponsor ID
- 2021P000774
- Conditions
- Alzheimer Disease (AD)
- Keywords
- Alzheimer's disease, Protollin, immune response
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- I-Mab Biopharma US Limited
- Study start
- 18 Nov 2021 (actual)
- Primary completion
- 22 Sep 2022 (actual)
- Study completion
- 21 Feb 2023 (actual)
- First posted
- 22 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In this research study investigators want to learn more about a new drug called nasal Protollin as a possible new treatment for Alzheimer's Disease (AD). In AD, there is accumulation in the brain of a toxic substance called amyloid. It is believed that this toxic substance causes brain cells to progressively waste away (degenerate) and die, causing a continuous decline in thinking, behavioral and social skills. Why amyloid accumulates is not completely understood.
The aim of this treatment is to remove toxic amyloid from the brain and prevent further degeneration. Although nasal Protollin has been given as part of vaccination programs, this is the first time Protollin will be given nasally (through the nose) in AD patients. Investigators aim to see if this way of giving the Protollin is safe and whether it stimulates the body's white blood cells to remove toxic amyloid from the brain and ultimately improve cognition. This will be a dose escalating (gradually increasing the dose in different subjects) study, which means we want to find the highest dose of Protollin that is safe to take. Protollin is not approved by the U.S. Food and Drug Administration (FDA). This means that Protollin can only be used in research studies.
This research study will compare Protollin to placebo. The placebo looks exactly like Protollin, but it does not contain any Protollin. During this study participants may get a placebo instead of Protollin. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- This is a randomized, double-blind, Phase I, ascending dose study evaluating four dose cohorts.
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Active comparator | Drug: ProtollinProtollin 0.1 mg or placebo |
| Cohort B | Active comparator | Drug: ProtollinProtollin 0.5 mg or placebo |
| Cohort C | Active comparator | Drug: ProtollinProtollin 1.0 mg or placebo |
| Cohort D | Active comparator | Drug: ProtollinProtollin 1.5 mg or placebo |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProtollinFor 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. | Drug | Cohort A, Cohort B, Cohort C, Cohort D |
Primary outcome
Safety and tolerability of ascending doses of nasal Protollin
Time frame: Day 1 (enrollment) to 180 days (end of study)
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2025.
- Derived from this study: PubMed 42248874Kolypetri P, da Silva P, Francisco RS Jr, Frenkel D, Cecere RR, Kiliaan PCJ, Montini F, Saxena S, Clementi WA, Liu X, Sun C, Bergmark RW, Singhal T, Saraceno TJ, Zimmermann J, Gale SA, Selkoe DJ, Chitnis T, Weiner HL. Nasal administration of Protollin enhances monocyte phagocytosis and decreases CD8+ T cell cytotoxicity in subjects with early Alzheimer's disease: a Phase 1 clinical trial. NPJ Aging. 2026 Jun 5. doi: 10.1038/s41514-026-00397-3. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Protollin in people with Alzheimer Disease (AD), run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of ascending doses of nasal Protollin (time frame: Day 1 (enrollment) to 180 days (end of study)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07187141, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2025; AzTrials last refreshed its copy on 7 Nov 2026.