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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease, Early Onset
• Intervention / Treatment: Drug: PMN310; Drug: Placebo

Detailed Description

This study is a Phase 1b, randomized, double-blind, placebo controlled, multi-ascending dose study of repeat doses of PMN310 to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of multiple intravenous infusions of PMN310 in patients with early Alzheimer's disease. This study will evaluate 3 dose levels (350 mg, 700 mg, and 1400 mg are planned). Patients will be randomly assigned 3:1, PMN310: placebo.

Each patient will receive PMN310 or placebo once every 28 days for a total of 12 infusions.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92614
      • Irvine Center for Clinical Research
    • Long Beach, California, United States, 90804
      • Healthy Brain Research
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Deerfield Beach, Florida, United States, 33442
      • Quantum Laboratories
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Miami, Florida, United States, 33126
      • Finlay Medical Research
    • Miami, Florida, United States, 33135
      • Gonzalez MD and Aswad MD Health Services, Optimus U Corp
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32803
      • Charter Research
    • Stuart, Florida, United States, 34997
      • Alzheimer's Research and Treatment Center
    • The Villages, Florida, United States, 32162
      • Charter Research
    • Wellington, Florida, United States, 33414
      • Alzheimer's Research and Treatment Center
    • Winter Park, Florida, United States, 32789
      • Conquest Research, LLC
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Memory Center, LLC
    • Decatur, Georgia, United States, 30030
      • CenExel iResearch, LLC
  • Massachusetts
    • Plymouth, Massachusetts, United States, 02360
      • Headlands Eastern MA LLC
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute of NJ
  • New York
    • Albany, New York, United States, 12208
      • Alzheimer's Disease Research Center
  • North Carolina
    • Matthews, North Carolina, United States, 28105
      • Flourish Research
  • Ohio
    • North Canton, Ohio, United States, 44720
      • Neuro Behavioral Clinical Research, Inc.
  • Pennsylvania
    • Plymouth Meeting, Pennsylvania, United States, 19462
      • Keystone Clinical Studies, LLC
  • Texas
    • Dallas, Texas, United States, 75231
      • Kerwin Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion 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 or 1.0 and memory box score ≥ 0.5 at Screening and Baseline
   3. MMSE score between ≥ 20 and 30 inclusive at Screening, and
   4. Either a positive amyloid PET scan within 12 months of Screening consistent with AD, or a positive amyloid PET during Screening.
4. Body mass index between 18 and 36 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).
   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. Patients taking low-dose (5mg) donepezil only require a stable dose for at least 6 weeks prior to baseline.
10. Gradual and progressive memory impairment for >12 months as reported by the patient or informant.
11. A positive result on the Lumipulse G p-tau217/β-Amyloid 1-42 Plasma Ratio test during Screening (when available). If results are indeterminate or unavailable, a patient with a plasma p-tau-217 result of ≥0.50 ng/L will be considered eligible.

Exclusion Criteria:

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 multisort 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 12 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 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 (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 PMN310 350 mg or placebo; PMN310 350 mg or placebo administered as a 60-minute infusion.	Drug: PMN310; A humanized immunoglobulin G1 (IgG1) monoclonal antibody; Drug: Placebo; 0.9% NaCl 100 mL
Experimental: Cohort 2 PMN310 700 mg or placebo; PMN310 700 mg or placebo administered as a 60-minute infusion.	Drug: PMN310; A humanized immunoglobulin G1 (IgG1) monoclonal antibody; Drug: Placebo; 0.9% NaCl 100 mL
Experimental: Cohort 3 PMN310 1400 mg or placebo; PMN310 1400 mg or placebo administered as a 60-minute infusion.	Drug: PMN310; A humanized immunoglobulin G1 (IgG1) monoclonal antibody; Drug: Placebo; 0.9% NaCl 100 mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of PMN310 following repeat intravenous infusions of PMN310	Number and severity of adverse events	Up to Day 337
Biomarker response to PMN310 following repeat intravenous infusions of PMN310	Mean change in plasma p-tau217 in response to repeat intravenous infusions of PMN310	Up to Day 337
Safety and tolerability of PMN310 following repeat intravenous infusions of PMN310	Percent of patients with symptomatic and/or non symptomatic amyloid-related imaging abnormalities	Up to Day 337

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pk profile of PMN310 with repeat dosing	Serum PK parameter area under the curve to the end of the dosing period (AUCtau)	Up to Day 337
Assessment of the immunogenicity of PMN310 following repeat intravenous infusions	Immunogenicity of PMN310 - anti-drug antibodies (ADAs) in serum	Up to Day 309
Assessment of biomarker response to PMN310	Mean change from baseline for amyloid PET	Up to Day 337
Assessment of cortical and hippocampal volume	Mean change from Baseline in cortical and hippocampal volume	Up to Day 337
Preliminary efficacy of repeat doses of PMN310 on CDR-SB	Mean change from Baseline in Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)	Up to Day 337
Pk profile of PMN310 with repeat dosing	Serum PK parameter concentration 4 weeks post-dose (C4W)	Up to Day 337
Pk profile of PMN310 with repeat dosing	Serum PK parameter maximum observed concentration (Cmax)	Up to Day 337
Pk profile of PMN310 with repeat dosing	Serum PK parameter trough concentration (Ctrough)	Up to Day 337
Pk profile of PMN310 with repeat dosing	Serum PK parameter time to reach maximum observed concentration (Tmax)	Up to Day 337
Pk profile of PMN310 with repeat dosing	Concentration of PMN310 in CSF at selected timepoints	Up to Day 337
Assessment of biomarker response to PMN310	Mean change from baseline for imaging	Up to Day 337
Assessment of biomarker response to PMN310	Mean change from baseline for plasma biomarkers	Up to Day 337
Assessment of biomarker response to PMN310	Mean change from baseline for CSF biomarkers	Up to Day 337
Preliminary efficacy of repeat doses of PMN310 on ADAS-Cog 14	Mean change from Baseline in Alzheimer's Disease Assessment Scale-Cognition 14 item (ADAS-Cog 14)	Up to Day 337
Preliminary efficacy of repeat doses of PMN310 on ADCS-ADL	Mean change from Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)	Up to Day 337
Preliminary efficacy of repeat doses of PMN310 on iADRS	Mean change from Baseline in Integrated Alzheimer's Disease Rating Score (iADRS)	Up to Day 337
Preliminary efficacy of repeat doses of PMN310 on CGI Scale	Mean change from Baseline in Clinical Global Impressions (CGI) Scale	Up to Day 337
Preliminary efficacy of repeat doses of PMN310 on MMSE	Mean change from Baseline in Mini-Mental State Examination (MMSE)	Up to Day 337
Pk profile of PMN310 with repeat dosing	Serum PK parameter steady state concentration (Css)	Up to Day 337
Pk profile of PMN310 with repeat dosing	Serum PK parameter terminal half-life (t1/2)	Up to Day 337
Assessment of the strength of the relationship between biomarker response and response on clinical outcomes following repeat intravenous infusions of PMN310	Correlation between changes from baseline of CSF biomarkers and amyloid PET with clinical outcomes	Up to Day 337
Assessment of the strength of the relationship between biomarker response and response on clinical outcomes following repeat intravenous infusions of PMN310	Correlation between changes from baseline of blood-based biomarkers	Up to Day 309 or early termination
Assessment of the strength of the relationship between biomarker response and response on clinical outcomes following repeat intravenous infusions of PMN310	Path analysis of the proportion of treatment effect on clinical outcomes explained by changes in biomarkers	Up to Day 337

Collaborators and Investigators

• Sponsor: ProMis Neurosciences, Inc
• Investigators: Principal Investigator: Kimball A Johnson, MD, CenExel iResearch, LLC; Principal Investigator: Cameron Olezene, MD, Keystone Clinical Studies, LLC; Principal Investigator: Linda Pao, MD, JEM Research Institute; Principal Investigator: Malisa Agard, MD, Conquest Research, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 19, 2024
• First Posted (Actual): December 27, 2024

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 10, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: PMN310-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No