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

Phase 1

Recruiting

• Conditions: Alzheimer Disease, Early Onset
• Interventions: Drug: PMN310; Drug: Placebo

• Registration Number: NCT06750432
• Lead Sponsor: ProMis Neurosciences, Inc

Brief Summary

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.

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 Timeline

• Study Start: 2024-12-13
• Study First Submitted: 2024-12-16
• Study First Submitted QC: 2024-12-19
• Study First Posted: 2024-12-27
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-28
• Last Update Posted: 2025-04-30
• Primary Completion: 2026-07
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 128

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 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.

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: >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 what 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2 PMN310 700 mg or placebo	PMN310	PMN310 700 mg or placebo administered as a 60-minute infusion.
Cohort 3 PMN310 1400 mg or placebo	PMN310	PMN310 1400 mg or placebo administered as a 60-minute infusion.
Cohort 1 PMN310 350 mg or placebo	PMN310	PMN310 350 mg or placebo administered as a 60-minute infusion.
Cohort 1 PMN310 350 mg or placebo	Placebo	PMN310 350 mg or placebo administered as a 60-minute infusion.
Cohort 2 PMN310 700 mg or placebo	Placebo	PMN310 700 mg or placebo administered as a 60-minute infusion.
Cohort 3 PMN310 1400 mg or placebo	Placebo	PMN310 1400 mg or placebo administered as a 60-minute infusion.

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of PMN310 following repeat intravenous infusions of PMN310	Up to Day 365	Percent of patients with symptomatic and/or non symptomatic amyloid-related imaging abnormalities
Biomarker response to PMN310 following repeat intravenous infusions of PMN310	Up to Day 365	Mean change in amyloid PET in response to repeat intravenous infusions of PMN310

Secondary Outcome Measures

Name	Time	Method
Pk profile of PMN310 with repeat dosing	Up to Day 365	Concentration of PMN310 in CSF at selected timepoints
Assessment of the immunogenicity of PMN310 following repeat intravenous infusions	Up to Day 365	Immunogenicity of PMN310 - anti-drug antibodies (ADAs) in serum
Assessment of biomarker response to PMN310	Up to Day 365	Mean change from baseline for CSF biomarkers
Assessment of cortical and hippocampal volume	Up to Day 365	Mean change from Baseline in cortical and hippocampal volume
Preliminary efficacy of repeat doses of PMN310 on CDR-SB	Up to Day 365	Mean change from Baseline in Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)
Preliminary efficacy of repeat doses of PMN310 on ADAS-Cog 14	Up to Day 365	Mean change from Baseline in Alzheimer's Disease Assessment Scale-Cognition 14 item (ADAS-Cog 14)
Preliminary efficacy of repeat doses of PMN310 on ADCS-ADL	Up to Day 365	Mean change from Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)
Preliminary efficacy of repeat doses of PMN310 on iADRS	Up to Day 365	Mean change from Baseline in Integrated Alzheimer's Disease Rating Score (iADRS)
Preliminary efficacy of repeat doses of PMN310 on CGI Scale	Up to Day 365	Mean change from Baseline in Clinical Global Impressions (CGI) Scale
Preliminary efficacy of repeat doses of PMN310 on MMSE	Up to Day 365	Mean change from Baseline in Mini-Mental State Examination (MMSE)

Trial Locations

Locations (20)

Irvine Center for Clinical Research; 🇺🇸 Irvine, California, United States

Healthy Brain Research; 🇺🇸 Long Beach, California, United States

JEM Research Institute; 🇺🇸 Atlantis, Florida, United States

Quantum Laboratories; 🇺🇸 Deerfield Beach, Florida, United States

Brain Matters Research; 🇺🇸 Delray Beach, Florida, United States

Finlay Medical Research; 🇺🇸 Miami, Florida, United States

Gonzalez MD and Aswad MD Health Services, Optimus U Corp; 🇺🇸 Miami, Florida, United States

Renstar Medical Research; 🇺🇸 Ocala, Florida, United States

Charter Research; 🇺🇸 The Villages, Florida, United States

Alzheimer's Research and Treatment Center; 🇺🇸 Wellington, Florida, United States

Conquest Research, LLC; 🇺🇸 Winter Park, Florida, United States

Columbus Memory Center, LLC; 🇺🇸 Columbus, Georgia, United States

CenExel iResearch, LLC; 🇺🇸 Decatur, Georgia, United States

Headlands Eastern MA LLC; 🇺🇸 Plymouth, Massachusetts, United States

Advanced Memory Research Institute of NJ; 🇺🇸 Toms River, New Jersey, United States

Alzheimer's Disease Research Center; 🇺🇸 Albany, New York, United States

Flourish Research; 🇺🇸 Matthews, North Carolina, United States

Neuro Behavioral Clinical Research, Inc.; 🇺🇸 North Canton, Ohio, United States

Keystone Clinical Studies, LLC; 🇺🇸 Plymouth Meeting, Pennsylvania, United States

Kerwin Medical Center; 🇺🇸 Dallas, Texas, United States