A Phase Ib/IIa, Randomized, Double Blind, Placebo-Controlled, Multiple Ascending Dose, Parallel-Group Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7126209 Following Intravenous Infusion in Patients With Prodromal or Mild to Moderate Alzheimer's Disease

Plain English Summary

Brainshuttle AD: A Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7126209 Following Intravenous Infusion in Participants With Prodromal or Mild to Moderate Alzheimer's Disease is a Phase 2 clinical trial sponsored by Hoffmann-La Roche studying Alzheimers Disease. This study tests a new drug called RO7126209, given through an IV, to see if it's safe and how it works in people with early or mild to moderate Alzheimer's disease. It is for individuals diagnosed with early-stage (prodromal) or mild to moderate Alzheimer's disease who have confirmed amyloid plaques in their brain. Participation involves receiving the study drug or a placebo (inactive substance) through an IV, undergoing regular medical check-ups, brain scans (MRI, PET), and spinal fluid tests (lumbar puncture). Currently, treatment options for early Alzheimer's focus on managing symptoms; this trial explores a potential disease-modifying therapy. The trial aims to enroll 241 participants.

Official Summary

The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of multiple-ascending intravenous (IV) doses of RO7126209 in participants with prodromal or mild to moderate Alzheimer's disease (AD), who are amyloid positive based on amyloid positron emission tomography (PET) scan.

Who Can Participate

Here is what you need to know about eligibility for this trial. Individuals with probable mild to moderate Alzheimer's or mild cognitive impairment due to Alzheimer's. Participants must have a confirmed amyloid PET scan and a specific range on cognitive tests (MMSE score 18-28, CDR-GS 0.5-2). Exclusion criteria include other neurological conditions, significant medical issues (heart, kidney, liver), inability to undergo MRI or lumbar puncture, or specific brain abnormalities on MRI. This trial is studying Alzheimers Disease, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures, such as the percentage of participants experiencing side effects and changes in brain amyloid levels, will help determine if the drug is safe and if it can reduce the bui The specific primary outcome measures are: Part 1, 2, 3, and 4: Percentage of Participants With Adverse Events (AEs) (Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 233 weeks); Part 3: Change From Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan (Up to approximately 24 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it investigates a new treatment that may target the underlying pathology of Alzheimer's disease, potentially filling a gap in therapies that currently only manage sympt Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Alzheimers Disease, where improved treatment options are needed.

Investor Insight

This Phase 2 trial for a novel Alzheimer's drug represents a significant investment in a large and growing market, with a competitive landscape focused on disease-modifying therapies; approval probabi Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the study drug RO7126209, potential risks, and if it's suitable for your specific condition. Be prepared for regular visits, including IV infusions, blood draws, cognitive tests, and potentially invasive procedures like lumbar punctures and brain scans. A reliable study partner who can accompany you and provide information about your daily functioning is required throughout the study. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: SEQUENTIAL
• Masking: QUADRUPLE
• Enrollment: 241 participants

Interventions

• DRUG: RO7126209 — RO7126209 will be administered intravenously as specified in each treatment arm.
• DRUG: Placebo — RO7126209-matching placebo will be administered intravenously as specified in each treatment arm.

Primary Outcomes

• Part 1, 2, 3, and 4: Percentage of Participants With Adverse Events (AEs) (Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 233 weeks)
• Part 3: Change From Baseline in Brain Amyloid Load as Measured by Amyloid Positron Emission Tomography (PET) Scan (Up to approximately 24 weeks)

Secondary Outcomes

• Part 1, 2, and 4: Change From Baseline in Brain Amyloid Load as Measured by Amyloid PET Scan (Part 1 and 2: Up to approximately 28 weeks; Part 4: Up to approximately 205 weeks)
• Part 1, 2, 3, and 4: Plasma Concentration of RO7126209 (Part 1 and 2: Up to approximately 32 weeks; Part 3: Up to approximately 24 weeks; Part 4: Up to approximately 209 weeks)
• Part 1, 2, 3, and 4: Cerebral Spinal Fluid (CSF) Concentration of RO7126209 (Part 1 and 2: Up to approximately 25 weeks; Part 3: Up to approximately 21 weeks; Part 4: Up to approximately 205 weeks)
• Part 1, 2, 3, and 4: Number of Participants With Anti-Drug Antibodies (ADAs) to RO7126209 (Part 1 and 2: Up to approximately 56 weeks; Part 3: Up to approximately 52 weeks; Part 4: Up to approximately 233 weeks)

Full Eligibility Criteria

Key inclusion criteria for part 1, 2 and 3:

* Ability to provide written consent signed by the participant
* Availability of a person (referred to as the "study partner") who: consents to participate throughout the duration of study, in the Investigator's judgment, has frequent and sufficient contact with the participant, is fluent in the language of the tests used at the study site
* Willingness and ability to complete all aspects of the study (including magnetic resonance imaging \[MRI\], lumbar puncture, clinical genotyping, and positron emission tomography \[PET\] imaging)
* Capable of completing assessments either alone or with the help of the study partner
* Adequate visual and auditory acuity, in the Investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)
* Probable mild to moderate AD dementia (consistent with National Institute on Aging-Alzheimer's Association \[NIA-AA\] core clinical criteria for probable AD dementia) or prodromal AD (consistent with the NIA-AA diagnostic criteria and guidelines for mild cognitive impairment due to AD)
* Screening Mini-Mental State Examination (MMSE) score of 18 to 28 points, inclusive, within 84 days before baseline
* Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, 1, or 2 within 84 days before baseline
* Positive amyloid PET scan (cut-off: \>50 Centiloid units) within 12 months before baseline
* In case of treatment with symptomatic AD medications, dosing regimen must be stable for at least 8 weeks prior to baseline and until randomization
* Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug
* Agreement not to participate in other research studies for the duration of this study
* Agree to apolipoprotein E (APOE) genotyping

Inclusion criteria for Part 4:

\- Completed the treatment period in Part 1, Part 2, or Part 3 of the study

Key exclusion criteria for part 1, 2 and 3:

* Any evidence of other relevant neurological condition, including other (non-AD) neurodegenerative and neuropsychiatric conditions, neurovascular brain disorders, seizure disorders, inflammatory and infectious disorders of the central nervous system, trauma and delirium, among several others
* Other relevant medical conditions including significant hematological diseases, any clinically significant ophthalmologic diseases, decreased visual acuity in either eye, with a BCVA letter score of less than 20 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or the Snellen equivalent of 20/400 if the ETDRS chart is not used
* Clinically significant cardiovascular diseases, chronic kidney disease, confirmed and unexplained impaired hepatic function, abnormal thyroid function, among several others
* History of hypersensitivity to biologic agents or any of the excipients in the formulation
* Clinically significant abnormalities (as judged by the Investigator) in laboratory test results (including complete blood count, chemistry panel, routine cerebrospinal fluid \[CSF\] parameters and urinalysis)
* MRI exclusion criteria: \>2 lacunar infarcts (including lacunar infarcts in the cerebellum), any territorial infarct \>1 cm\^3, any white matter lesion that corresponds to an overall Fazekas score of 3 that requires at least one confluent hyperintense lesion on the fluid-attenuated inversion recovery (FLAIR) sequence, which is ≥20 mm in any dimension
* More than 4 microhemorrhages on MRI and/or presence of any focal area of leptomeningeal hemosiderosis based on the review performed by the central MRI reader prior to randomization
* Presence of any other significant cerebral abnormalities, including amyloid-related imaging abnormality-edema/effusion (ARIA-E), as assessed on MRI
* Inability to tolerate MRI procedures or contraindication to MRI
* Inability to undergo ophthalmological assessments
* Contraindication to lumbar puncture
* Contraindication to having a PET scan

Exclusion criteria for Part 4:

* Prematurely discontinued from the treatment period for study (i.e., before the start of the follow-up period of Part 1, Part 2, or Part 3) for any reason or meeting discontinuation criteria before the baseline visit of Part 4.
* Received any active investigational treatment other than RO7126209 during or since completion of Part 1, Part 2 or Part 3
* Any passive immunotherapy (immunoglobulin) since completion of Part 1, Part 2, or Part 3 that is meant to prevent or postpone cognitive decline.
* Use of anti-coagulation medications - Evidence of ongoing ARIA-E. In this case participant may enroll into Part 4 once the ARIA-E is resolved - Evidence of ongoing infusion-related reaction (IRR) or hypersensitivity reaction. In this case participant may enroll into Part 4 once the IRR is resolved.
* MRI evidence of any of the following at OLE baseline: evidence of ongoing ARIA-E, any ARIA-H (leptomeningeal hemosiderosis or microhemorr

Trial Locations

• JEM Research LLC, Atlantis, Florida, United States
• K2 Medical Research-Winter Garden, Clermont, Florida, United States
• K2 Medical Research - The Villages, Lady Lake, Florida, United States
• K2 Medical Research, LLC, Maitland, Florida, United States
• Optimus U Corp, Miami, Florida, United States
• Charter Research - Winter Park/Orlando, Orlando, Florida, United States
• Advent Health Orlando, Orlando, Florida, United States
• Alzheimer's Research and Treatment Center, Stuart, Florida, United States
• Charter Research - Lady Lake/The Villages, The Villages, Florida, United States
• Alzheimer?s Research and Treatment Center, Wellington, Florida, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Alzheimer's Disease
• Mild Cognitive Impairment
• Dementia
• Neurodegenerative Diseases
• Amyloidosis
• Cognitive Impairment
• Neurology
• Geriatrics
• Brain Health
• Central Nervous System Disorders

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