Study With Lu AF87908 in Healthy Participants and Participants With Alzheimer's Disease

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety of a single dose of Lu AF87908, how well it is tolerated and what the body does to the drug in healthy participants and participants with Alzheimer's disease.

Detailed Description
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The study will be divided into three parts: Part A, Part B and Part C. Part A consists of up to 6 sequential cohorts (Cohorts A1 to A6): -Cohorts A1 to A6: 8 healthy participants per cohort (aiming for an equal number of men and women): 6 randomized to Lu AF87908 and 2 randomized to placebo. Part B consists of up to 3 sequential cohorts (Cohorts B1 to B3): -Cohorts B1 to B3: 4 Japanese and 4 Chinese healthy participants per cohort: 6 participants randomized to Lu AF87908 and 2 participants randomized to placebo. Part C consists of 2 sequential cohorts (Cohorts C1 and C4): -Cohort C1 will consist of 6 participants with Alzheimer's disease with 3:1 randomization scheme for active: placebo. Cohort C4 will consist of up to 8 participants. Cohort C4 participants will be randomized based on the randomization scheme from Cohort C1.

Official Title
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Interventional, Randomized, Double-blind, Placebo-controlled, Single-ascending-dose Study Investigating the Safety, Tolerability, and Pharmacokinetic Properties of Lu AF87908 in Healthy Subjects and Patients With Alzheimer's Disease

Conditions
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Healthy, Alzheimer Disease

Intervention / Treatment
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* Drug: Lu AF87908
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Healthy Participants: -Men and women ≥18 and ≤65 years of age with a body mass index (BMI) ≥18 and ≤32 kilograms (kg)/square meter (m^2) and a minimum weight of 50 kg. Participants with Alzheimer's disease: Men and women with a clinical diagnosis of Alzheimer's disease, Stages 3-4 according to the FDA guidelines. Mini-Mental State Examination (MMSE) of 15-30. Clinical Dementia Scale (CDR) global score up to and including 2.0. Confirmed or determined (via amyloid positron emission tomography [PET] scan) to be amyloid positive. If on FDA approved Alzheimer's disease medication, the treatment has been stable for 4 months prior to Day 1. -≥50 years of age. BMI ≥18 and ≤40 kg/m^2 and a minimum weight of 50 kg. Exclusion criteria: Clinically relevant structural brain abnormality as assessed using magnetic resonance imaging (MRI). Any past or current treatment with an anti-Abeta or anti-tau active vaccine. Any past or current treatment with a monoclonal anti-tau antibody or a tau anti-sense oligomer within the last 6 months. Treatment with covid-19, influenza or pneumonia vaccine within the last 30 days prior to dosing of investigational medicinal product (IMP). Other eligibility criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Lu AF87908 or Placebo<br>Participants in Cohorts A1 to A6 will receive a single dose of either Lu AF87908 or matching placebo at specific dose levels on Day 1. | Drug: Lu AF87908<br>* Lu AF87908 concentrate for solution for intravenous (IV) infusion<br>Drug: Placebo<br>* Concentrate for solution for IV infusion<br>|
| Experimental: Part B: Lu AF87908 or Placebo<br>Participants in Cohorts B1 to B3 will receive a single dose of either Lu AF87908 or matching placebo at specific dose levels on Day 1. | Drug: Lu AF87908<br>* Lu AF87908 concentrate for solution for intravenous (IV) infusion<br>Drug: Placebo<br>* Concentrate for solution for IV infusion<br>|
| Experimental: Part C: Lu AF87908 or Placebo<br>Participants in Cohorts C1 and C4 will receive a single dose of either Lu AF87908 or matching placebo at specific dose levels on Day 1. | Drug: Lu AF87908<br>* Lu AF87908 concentrate for solution for intravenous (IV) infusion<br>Drug: Placebo<br>* Concentrate for solution for IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment Emergent Adverse Events | Safety and tolerability based on the safety assessments (clinical safety laboratory tests, vital signs, weight, ECG parameters and physical examination) | From Day 0 to Day 84 | 
| AUC(0-t) of Lu AF87908 | Area under the plasma concentration curve for Lu AF87908 | From Day 0 to Day 84 | 
| Cmax of Lu AF87908 | Maximum observed plasma concentration for Lu AF87908 | From Day 0 to Day 84 | 
| Tmax Lu AF87908 | Nominal time of occurrence of Cmax of Lu AF97908 in plasma | From Day 0 to Day 84 |