ACTIVE_NOT_RECRUITING

PMN310 in Patients With Early Alzheimer's Disease (PRECISE-AD)

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This Phase 1b study aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of multiple IV infusions of PMN310 in patients with early Alzheimer's disease.

Official Title

A Phase 1b, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PMN310 in Patients With Early Alzheimer's Disease

Quick Facts

Study Start:2024-12-13

Study Completion:2026-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06750432

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:50 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Patient and caregiver provide written informed consent. 2. Ambulatory male or female ≥ 50 years of age with adequate visual and auditory abilities to perform the cognitive and functional assessments in the opinion of the Investigator. 3. Meets all of the following clinical criteria for mild cognitive impairment (MCI) due to AD or mild AD dementia at Screening: 1. National Institute on Aging-Alzheimer's Association criteria for MCI due to AD or mild AD dementia (Stage 3 and 4) 2. Global Clinical Dementia Rating (CDR) of 0.5 1.0 and memory box score ≥ 0.5 at Screening and Baseline 3. Objective impairment in episodic memory as indicated by at least 1 standard deviation (SD) below age-adjusted mean in the Wechsler Memory Scale IV-Logical Memory (subscale) II 4. MMSE score between ≥ 20 and 28 inclusive at Screening, and 5. Either a positive amyloid PET scan within 6 months of Screening consistent with AD, or a positive amyloid PET during Screening. 4. Body mass index between 18.5 and 35 kg/m2 inclusive. 5. Patients of childbearing potential must meet the following criteria: 1. Male and female patients with reproductive potential must be willing to use an approved double barrier contraceptive method (e.g., condom plus intrauterine device, condom plus hormonal contraception, or double barrier device) during and for 120 days after the last dose of study drug 2. Females of childbearing potential must have a negative serum pregnancy test during Screening, a negative urine pregnancy test prior to each dose, and not currently be breastfeeding. 6. Patients of non-childbearing potential must meet 1 of the following: 1. Post-menopausal female (i.e., 12 consecutive months of spontaneous amenorrhea, age \> 51 years, and follicle-stimulating hormone \> 30 mIU/mL) 2. Surgically sterile (i.e., bilateral oophorectomy or hysterectomy). 7. Has a reliable caregiver who agrees to accompany the patient at study visits, accurately report patient's status, provide feedback on functional and safety assessments, and ensure compliance to study requirements. 8. Confirmed to have acceptable venous access for blood collections and IV administration of study drug (i.e., PMN310 or placebo). 9. Patients taking Food and Drug Administration-approved acetylcholinesterase inhibitors or memantine are allowed as long as the dose has been stable for at least 3 months prior to Screening.	1. Living in a continuous care or long-term care nursing facility. Patients in outpatient living at home or in an assisted living facility are eligible for the study. 2. Medical or neurological condition (other than AD; i.e., Parkinson's disease, Huntington's disease, frontal temporal dementia, dementia with Lewy bodies) judged to be contributing to the patient's cognitive impairment. 3. Laboratory and electrocardiogram (ECG) abnormalities: 1. QT (QTcF) interval \> 450 msec (males) or \> 470 msec (females) during Screening 2. Alanine aminotransferase ≥ 2 × upper limit of normal (ULN); aspartate aminotransferase ≥ 2 × ULN; total bilirubin ≥1.5 × ULN during Screening 3. Creatinine clearance \< 30mL/min during Screening. 4. In the opinion of the Investigator, any clinically significant current or relevant history of physical or psychiatric illness (including suicidal risk, ideation, behavior, or suicide attempts), any medical disorder that may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures. 5. Clinically significant recurrent disease or unstable disease that could affect the action, absorption, or disposition of the investigational product, or could affect clinical or laboratory assessments, such as (but not limited to) the following: 1. History of unstable angina, myocardial infarction, chronic heart failure, or clinically significant conduction abnormalities within 1 year prior to Screening 2. Indication of clinically significant impairment of renal or liver function, including hepatitis B surface antigen, or hepatitis C virus antibody at Screening 3. Poorly managed hypertension (systolic \> 160 mmHg and/or diastolic \> 95 mmHg) or hypotension (systolic \< 90 mmHg and/or diastolic \< 60 mmHg). Two repeated assessments during Screening are allowed 4. Known uncontrolled diabetes defined by hemoglobin A1c \> 7.5 or insulin dependent diabetes. 6. Experienced a significant systemic illness, as judged by the Investigator, within 30 days of the first dose of study drug. 7. Seizure in the 3 years prior to Screening. 8. History of a clinically significant medical condition that would interfere with the patient's ability to comply with study instructions, would place the patient at increased risk, or might confound the interpretation of the study results. 9. History of prior malignancy (except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix). 10. Brain MRI with evidence of any of the following findings at Screening: \>4 microhemorrhages; \> 1 lobar microhemorrhage, area of superficial siderosis; subarachnoid hemorrhage; any other hemorrhage \> 10 mm; \> 2 lacunar infarcts or cortical infarct; subjects with severe perivascular spaces or with white matter hyperintensities in a multisport pattern will require PI review prior to inclusion. 11. History of stroke or transient ischemic attack within 12 months prior to Screening. 12. Contraindication to PET or brain MRI. 13. Negative PET scan with any amyloid-targeting ligand within 6 months of Screening or during Screening. 14. Pregnant or breastfeeding. 15. History of alcohol abuse and/or other substance abuse within 12 months prior to dosing with study drug. 16. Positive test for alcohol (using an alcohol breath test) or illicit drugs of abuse at Screening. 17. Documented history of human immunodeficiency virus antibody. 18. Coronavirus disease 2019 (COVID-19) infection within 2 weeks of Screening or ongoing symptoms of COVID-19 at Screening. 19. Currently receiving an anti-amyloid treatment, either marketed (aducanumab, lecanemab, donanemab) or investigational or has received anti amyloid therapy within 9 months prior to Screening. In the case of investigational treatment, those known to have received placebo will not be excluded. 20. Contraindication to undergoing lumbar puncture (LP) including: sensitivity to local anesthetic, international normalized ratio (INR) \> 1.4 or other coagulopathy, platelet cell count of \< 120,000/µL, infection at the desired LP site, current use of anti-coagulant medication except for low dose aspirin, degenerative arthritis, spinal scoliosis, back surgery, suspected increased intracranial pressure on history or neurologic exam, non-communicating hydrocephalus or intracranial mass, or prior history of spinal mass or trauma and/or other known clinically significant spinal abnormalities. 21. Donated blood or blood products (e.g., plasma, platelets) within 56 days prior to first dose of study drug. 22. Received an investigational active agent (e.g., not placebo) within the last 30 days or 5 half-lives, whichever is longer (if known). 23. Known history of severe allergic reaction or hypersensitivity to any components of the PMN310 infusion.

Inclusion Criteria

Exclusion Criteria

1. Patient and caregiver provide written informed consent.
2. Ambulatory male or female ≥ 50 years of age with adequate visual and auditory abilities to perform the cognitive and functional assessments in the opinion of the Investigator.
3. Meets all of the following clinical criteria for mild cognitive impairment (MCI) due to AD or mild AD dementia at Screening:
1. National Institute on Aging-Alzheimer's Association criteria for MCI due to AD or mild AD dementia (Stage 3 and 4)
2. Global Clinical Dementia Rating (CDR) of 0.5 1.0 and memory box score ≥ 0.5 at Screening and Baseline
3. Objective impairment in episodic memory as indicated by at least 1 standard deviation (SD) below age-adjusted mean in the Wechsler Memory Scale IV-Logical Memory (subscale) II
4. MMSE score between ≥ 20 and 28 inclusive at Screening, and
5. Either a positive amyloid PET scan within 6 months of Screening consistent with AD, or a positive amyloid PET during Screening.
4. Body mass index between 18.5 and 35 kg/m2 inclusive.
5. Patients of childbearing potential must meet the following criteria:
1. Male and female patients with reproductive potential must be willing to use an approved double barrier contraceptive method (e.g., condom plus intrauterine device, condom plus hormonal contraception, or double barrier device) during and for 120 days after the last dose of study drug
2. Females of childbearing potential must have a negative serum pregnancy test during Screening, a negative urine pregnancy test prior to each dose, and not currently be breastfeeding.
6. Patients of non-childbearing potential must meet 1 of the following:
1. Post-menopausal female (i.e., 12 consecutive months of spontaneous amenorrhea, age \> 51 years, and follicle-stimulating hormone \> 30 mIU/mL)
2. Surgically sterile (i.e., bilateral oophorectomy or hysterectomy).
7. Has a reliable caregiver who agrees to accompany the patient at study visits, accurately report patient's status, provide feedback on functional and safety assessments, and ensure compliance to study requirements.
8. Confirmed to have acceptable venous access for blood collections and IV administration of study drug (i.e., PMN310 or placebo).
9. Patients taking Food and Drug Administration-approved acetylcholinesterase inhibitors or memantine are allowed as long as the dose has been stable for at least 3 months prior to Screening.

1. Living in a continuous care or long-term care nursing facility. Patients in outpatient living at home or in an assisted living facility are eligible for the study.
2. Medical or neurological condition (other than AD; i.e., Parkinson's disease, Huntington's disease, frontal temporal dementia, dementia with Lewy bodies) judged to be contributing to the patient's cognitive impairment.
3. Laboratory and electrocardiogram (ECG) abnormalities:
1. QT (QTcF) interval \> 450 msec (males) or \> 470 msec (females) during Screening
2. Alanine aminotransferase ≥ 2 × upper limit of normal (ULN); aspartate aminotransferase ≥ 2 × ULN; total bilirubin ≥1.5 × ULN during Screening
3. Creatinine clearance \< 30mL/min during Screening.
4. In the opinion of the Investigator, any clinically significant current or relevant history of physical or psychiatric illness (including suicidal risk, ideation, behavior, or suicide attempts), any medical disorder that may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
5. Clinically significant recurrent disease or unstable disease that could affect the action, absorption, or disposition of the investigational product, or could affect clinical or laboratory assessments, such as (but not limited to) the following:
1. History of unstable angina, myocardial infarction, chronic heart failure, or clinically significant conduction abnormalities within 1 year prior to Screening
2. Indication of clinically significant impairment of renal or liver function, including hepatitis B surface antigen, or hepatitis C virus antibody at Screening
3. Poorly managed hypertension (systolic \> 160 mmHg and/or diastolic \> 95 mmHg) or hypotension (systolic \< 90 mmHg and/or diastolic \< 60 mmHg). Two repeated assessments during Screening are allowed
4. Known uncontrolled diabetes defined by hemoglobin A1c \> 7.5 or insulin dependent diabetes.
6. Experienced a significant systemic illness, as judged by the Investigator, within 30 days of the first dose of study drug.
7. Seizure in the 3 years prior to Screening.
8. History of a clinically significant medical condition that would interfere with the patient's ability to comply with study instructions, would place the patient at increased risk, or might confound the interpretation of the study results.
9. History of prior malignancy (except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix).
10. Brain MRI with evidence of any of the following findings at Screening: \>4 microhemorrhages; \> 1 lobar microhemorrhage, area of superficial siderosis; subarachnoid hemorrhage; any other hemorrhage \> 10 mm; \> 2 lacunar infarcts or cortical infarct; subjects with severe perivascular spaces or with white matter hyperintensities in a multisport pattern will require PI review prior to inclusion.
11. History of stroke or transient ischemic attack within 12 months prior to Screening.
12. Contraindication to PET or brain MRI.
13. Negative PET scan with any amyloid-targeting ligand within 6 months of Screening or during Screening.
14. Pregnant or breastfeeding.
15. History of alcohol abuse and/or other substance abuse within 12 months prior to dosing with study drug.
16. Positive test for alcohol (using an alcohol breath test) or illicit drugs of abuse at Screening.
17. Documented history of human immunodeficiency virus antibody.
18. Coronavirus disease 2019 (COVID-19) infection within 2 weeks of Screening or ongoing symptoms of COVID-19 at Screening.
19. Currently receiving an anti-amyloid treatment, either marketed (aducanumab, lecanemab, donanemab) or investigational or has received anti amyloid therapy within 9 months prior to Screening. In the case of investigational treatment, those known to have received placebo will not be excluded.
20. Contraindication to undergoing lumbar puncture (LP) including: sensitivity to local anesthetic, international normalized ratio (INR) \> 1.4 or other coagulopathy, platelet cell count of \< 120,000/µL, infection at the desired LP site, current use of anti-coagulant medication except for low dose aspirin, degenerative arthritis, spinal scoliosis, back surgery, suspected increased intracranial pressure on history or neurologic exam, non-communicating hydrocephalus or intracranial mass, or prior history of spinal mass or trauma and/or other known clinically significant spinal abnormalities.
21. Donated blood or blood products (e.g., plasma, platelets) within 56 days prior to first dose of study drug.
22. Received an investigational active agent (e.g., not placebo) within the last 30 days or 5 half-lives, whichever is longer (if known).
23. Known history of severe allergic reaction or hypersensitivity to any components of the PMN310 infusion.

Contacts and Locations

Study Locations (Sites)

Irvine Center for Clinical Research

Irvine, California, 92614

United States

Healthy Brain Research

Long Beach, California, 90804

United States

JEM Research Institute

Atlantis, Florida, 33462

United States

Quantum Laboratories

Deerfield Beach, Florida, 33442

United States

Brain Matters Research

Delray Beach, Florida, 33445

United States

Finlay Medical Research

Miami, Florida, 33126

United States

Gonzalez MD and Aswad MD Health Services, Optimus U Corp

Miami, Florida, 33135

United States

Renstar Medical Research

Ocala, Florida, 34470

United States

Charter Research

Orlando, Florida, 32803

United States

Alzheimer's Research and Treatment Center

Stuart, Florida, 34997

United States

Charter Research

The Villages, Florida, 32162

United States

Alzheimer's Research and Treatment Center

Wellington, Florida, 33414

United States

Conquest Research, LLC

Winter Park, Florida, 32789

United States

Columbus Memory Center, LLC

Columbus, Georgia, 31909

United States

CenExel iResearch, LLC

Decatur, Georgia, 30030

United States

Headlands Eastern MA LLC

Plymouth, Massachusetts, 02360

United States

Advanced Memory Research Institute of NJ

Toms River, New Jersey, 08755

United States

Alzheimer's Disease Research Center

Albany, New York, 12208

United States

Flourish Research

Matthews, North Carolina, 28105

United States

Neuro Behavioral Clinical Research, Inc.

North Canton, Ohio, 44720

United States

Keystone Clinical Studies, LLC

Plymouth Meeting, Pennsylvania, 19462

United States

Kerwin Medical Center

Dallas, Texas, 75231

United States

Collaborators and Investigators

Sponsor: ProMis Neurosciences, Inc

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-13

Study Completion Date2026-12

Study Record Updates

Study Start Date2024-12-13

Study Completion Date2026-12

Terms related to this study

Additional Relevant MeSH Terms

Alzheimer Disease, Early Onset