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
Overview
- Phase
- Phase 1
- Intervention
- PMN310
- Conditions
- Alzheimer Disease, Early Onset
- Sponsor
- ProMis Neurosciences, Inc
- Enrollment
- 144
- Locations
- 20
- Primary Endpoint
- Safety and tolerability of PMN310 following repeat intravenous infusions of PMN310
- Status
- Active, not recruiting
- Last Updated
- 4 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient and caregiver provide written informed consent.
- •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.
- •Meets all of the following clinical criteria for mild cognitive impairment (MCI) due to AD or mild AD dementia at Screening:
- •National Institute on Aging-Alzheimer's Association criteria for MCI due to AD or mild AD dementia (Stage 3 and 4)
- •Global Clinical Dementia Rating (CDR) of 0.5 1.0 and memory box score ≥ 0.5 at Screening and Baseline
- •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
- •MMSE score between ≥ 20 and 28 inclusive at Screening, and
- •Either a positive amyloid PET scan within 6 months of Screening consistent with AD, or a positive amyloid PET during Screening.
- •Body mass index between 18.5 and 35 kg/m2 inclusive.
- •Patients of childbearing potential must meet the following criteria:
Exclusion Criteria
- •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.
- •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.
- •Laboratory and electrocardiogram (ECG) abnormalities:
- •QT (QTcF) interval \> 450 msec (males) or \> 470 msec (females) during Screening
- •Alanine aminotransferase ≥ 2 × upper limit of normal (ULN); aspartate aminotransferase ≥ 2 × ULN; total bilirubin ≥1.5 × ULN during Screening
- •Creatinine clearance \< 30mL/min during Screening.
- •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.
- •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:
- •History of unstable angina, myocardial infarction, chronic heart failure, or clinically significant conduction abnormalities within 1 year prior to Screening
- •Indication of clinically significant impairment of renal or liver function, including hepatitis B surface antigen, or hepatitis C virus antibody at Screening
Arms & Interventions
Cohort 1 PMN310 350 mg or placebo
PMN310 350 mg or placebo administered as a 60-minute infusion.
Intervention: PMN310
Cohort 1 PMN310 350 mg or placebo
PMN310 350 mg or placebo administered as a 60-minute infusion.
Intervention: Placebo
Cohort 2 PMN310 700 mg or placebo
PMN310 700 mg or placebo administered as a 60-minute infusion.
Intervention: PMN310
Cohort 2 PMN310 700 mg or placebo
PMN310 700 mg or placebo administered as a 60-minute infusion.
Intervention: Placebo
Cohort 3 PMN310 1400 mg or placebo
PMN310 1400 mg or placebo administered as a 60-minute infusion.
Intervention: PMN310
Cohort 3 PMN310 1400 mg or placebo
PMN310 1400 mg or placebo administered as a 60-minute infusion.
Intervention: Placebo
Outcomes
Primary Outcomes
Safety and tolerability of PMN310 following repeat intravenous infusions of PMN310
Time Frame: 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
Time Frame: Up to Day 365
Mean change in amyloid PET in response to repeat intravenous infusions of PMN310
Secondary Outcomes
- Pk profile of PMN310 with repeat dosing(Up to Day 365)
- Assessment of the immunogenicity of PMN310 following repeat intravenous infusions(Up to Day 365)
- Assessment of biomarker response to PMN310(Up to Day 365)
- Assessment of cortical and hippocampal volume(Up to Day 365)
- Preliminary efficacy of repeat doses of PMN310 on CDR-SB(Up to Day 365)
- Preliminary efficacy of repeat doses of PMN310 on ADAS-Cog 14(Up to Day 365)
- Preliminary efficacy of repeat doses of PMN310 on ADCS-ADL(Up to Day 365)
- Preliminary efficacy of repeat doses of PMN310 on iADRS(Up to Day 365)
- Preliminary efficacy of repeat doses of PMN310 on CGI Scale(Up to Day 365)
- Preliminary efficacy of repeat doses of PMN310 on MMSE(Up to Day 365)