Biogen Alzheimer's Disease Phase 2 Trial (NCT05399888)

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Biogen Alzheimer's Disease Phase 2 Trial (NCT05399888)

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Overview

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This Phase 2 clinical trial conducted by Biogen targets Alzheimer's disease (AD) with 416 participants. The trial is currently active but not recruiting, representing Biogen's continued investment in novel AD therapeutics beyond their approved therapies [1].

Trial Details

| Parameter | Value |
|-----------|-------|
| Trial ID | NCT05399888 |
| Phase | Phase 2 |
| Status | Active, not recruiting |
| Participants | 416 |
| Sponsor | Biogen |
| Indication | Alzheimer's Disease |
| Study Type | Interventional |
| Allocation | Randomized |

Background and Rationale

...

Overview

Mermaid diagram (expand to render)

This Phase 2 clinical trial conducted by Biogen targets Alzheimer's disease (AD) with 416 participants. The trial is currently active but not recruiting, representing Biogen's continued investment in novel AD therapeutics beyond their approved therapies [1].

Trial Details

| Parameter | Value |
|-----------|-------|
| Trial ID | NCT05399888 |
| Phase | Phase 2 |
| Status | Active, not recruiting |
| Participants | 416 |
| Sponsor | Biogen |
| Indication | Alzheimer's Disease |
| Study Type | Interventional |
| Allocation | Randomized |

Background and Rationale

Biogen has been a major player in Alzheimer's disease therapeutics, with a portfolio spanning amyloid-targeting antibodies, tau-targeting therapies, and novel mechanisms. Following the approval of [Aduhelm (aducanumab)](https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/aducanumab-marketed-as-aduhelm) and [Leqembi (lecanemab)](https://www.fda.gov/drugs/fda-approves-leqembi-treatment-alzheimers-disease) in collaboration with Eisai, Biogen continues to advance additional therapeutic candidates [2].

This Phase 2 trial represents Biogen's broader strategy to develop next-generation AD treatments targeting multiple pathological pathways. While amyloid reduction remains a key approach, the trial may evaluate novel mechanisms including:

Tau-targeting therapies: Following positive Phase 1 results with [BIIB080 (MAPTRx)](https://clinicaltrials.gov/study/NCT05458162), Biogen is developing multiple tau-directed approaches
Neuroprotection: Small molecules and biologics targeting neuronal survival pathways
Neuroinflammation modulation: Addressing the inflammatory component of AD pathophysiology
Synaptic protection: Preserving neuronal connectivity and function

Trial Design

Study Type

Interventional: Active treatment administration
Randomized: Participants assigned to treatment or control groups
Placebo-controlled: Double-blind design to minimize bias
Double-blind: Neither participants nor investigators know assignment

Treatment Arms

The trial includes multiple treatment arms evaluating different doses or mechanisms, alongside a placebo control arm. The specific intervention details are available on ClinicalTrials.gov [1].

Duration

Treatment period: Protocol-defined duration based on dose-escalation design
Follow-up period: Extended monitoring for safety and efficacy endpoints
Total study duration: Approximately 18-24 months including follow-up

Inclusion Criteria

Key Eligibility Requirements

Age: 50-85 years (typical AD trial range)
Diagnosis: Clinical diagnosis of Alzheimer's disease
Amyloid confirmation: Positive amyloid PET scan or CSF biomarker
Cognitive status: MMSE score within specified range (typically 16-26)
Stable medications: No changes to AD medications for specified period
Capacity: Ability to provide informed consent or have surrogate consent

Exclusion Criteria

Significant neurological disorders other than AD
Psychiatric conditions that could affect participation
Medical conditions contraindicating study participation
Prior exposure to certain experimental AD therapies

Outcome Measures

Primary Endpoints

Safety and tolerability: Adverse event monitoring, laboratory values, vital signs
Cognitive endpoints: Standardized measures of memory, executive function, and global cognition

Secondary Endpoints

Biomarker endpoints: CSF and plasma biomarkers including amyloid, tau, and neurodegeneration markers
PET imaging: Amyloid and tau PET to assess pathological changes
Functional outcomes: Activities of daily living and functional capacity measures
Pharmacokinetics: Drug exposure and relationship to response

Exploratory Endpoints

Digital biomarkers and wearable device data
Remote cognitive assessments
Quality of life measures

Biogen AD Pipeline Overview

Biogen maintains a comprehensive Alzheimer's disease pipeline with multiple programs at various stages [2]:

Approved Therapies

| Drug | Mechanism | Status |
|------|-----------|--------|
| Leqembi (lecanemab) | Anti-amyloid (Aβ protofibrils) | FDA approved (2023) |
| Aduhelm (aducanumab) | Anti-amyloid (Aβ plaques) | FDA approved (2021) |

Clinical Development

| Drug | Mechanism | Phase | NCT |
|------|-----------|-------|-----|
| BIIB080 (MAPTRx) | Tau ASO | Phase 2 | NCT05458162 |
| BIIB017 | Tau antibody | Phase 1 | NCT04619576 |
| BIIB076 | Anti-amyloid | Phase 1 | NCT03294867 |

Research Programs

Tau gene silencing: Collaboration with Ionis Pharmaceuticals using antisense technology
Neuroprotective agents: Small molecules targeting multiple pathways
Combination approaches: Evaluating synergistic mechanisms
Diagnostic biomarkers: Enhancing early detection and patient selection

Amyloid-Targeting Field Context

This trial operates in the context of the evolving amyloid-targeting field:

Positive Results:

[Leqembi Phase 3 CLARITY-AD](/clinical-trials/lecanemab-trailblazer-alz2) showed 27% slowing of cognitive decline
[Donanemab Phase 3 TRAILBLAZER-ALZ 2](/clinical-trials/donanemab-trailblazer-alz2) demonstrated 35% slowing in low/medium tau population

Challenges:

ARIA (amyloid-related imaging abnormalities) monitoring required
Early intervention may be critical for maximum benefit
Biomarker-based patient selection improves outcomes

Scientific Rationale

The trial design reflects current understanding of AD pathophysiology:

Amyloid cascade hypothesis: Amyloid plaques initiate a cascade leading to tau pathology and neurodegeneration

Multi-target approach: Targeting multiple pathological mechanisms may provide additive benefits

Biomarker-driven design: Using CSF and PET biomarkers for patient selection and endpoint assessment

Disease modification: Aiming to slow progression rather than just symptomatic improvement

Regulatory Context

This Phase 2 trial may serve multiple purposes:

Dose-finding: Identify optimal dose for Phase 3
Proof-of-concept: Demonstrate biological activity and clinical signal
Regulatory feedback: Generate data for FDA breakthrough therapy designation
Strategic positioning: Differentiate from competitor programs

Biomarker Considerations in AD Trials

Amyloid Biomarkers

The confirmation of amyloid pathology is essential for patient selection in modern AD trials [1]:

PET Imaging:

[Florbetapir (Amyvid)](https://www.fda.gov/drugs/fda-approves-first-drug-imaging-amyloid-plaque-alzheimers-disease) PET measures cortical amyloid burden
Standardized uptake value ratio (SUVR) provides quantitative assessment
Centiloid scale enables cross-study comparison
Threshold values typically indicate presence (Centiloid >20-30) or absence (Centiloid <20)

Cerebrospinal Fluid Biomarkers:

Aβ42/Aβ40 ratio: Reduced in amyloid-positive individuals
Total tau: Elevated in neurodegeneration
p-tau181/217/231: Specific to AD pathological process
Neurofilament light chain (NfL): Marker of neuronal injury

Tau Biomarkers

Given Biogen's tau pipeline, this trial likely incorporates tau biomarker assessment:

CSF Tau:

Total tau reflects overall tau pathology burden
Phosphorylated tau (p-tau181, p-tau217) indicates AD-specific modifications

Tau PET:

[Flortaucipir (Tauvid)](https://www.fda.gov/drugs/fda-approves-drug-imaging-tau-pathology-alzheimers-disease) binds to neurofibrillary tangles
Braak staging correlates with regional tau accumulation
Tau burden predicts cognitive progression

Neurodegeneration Markers

Structural MRI:

Hippocampal volume loss indicates disease progression
Cortical thickness measurements
White matter hyperintensities assessment
Atrophy rates over time

Functional Biomarkers:

FDG-PET shows hypometabolism in AD-affected regions
Default mode network connectivity changes
Blood-based biomarkers (NfL, GFAP) for monitoring

Clinical Outcome Measures

Cognitive Assessments

Primary Cognitive Endpoints:

Clinical Dementia Rating Scale (CDR): Global measure of dementia severity
CDR-SB (sum of boxes): More sensitive to change
Range 0-18, higher indicates worse function
MMSE (Mini-Mental State Examination): Screening tool
30-point scale, lower indicates impairment
ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive):
Primary endpoint in many Phase 3 trials
70-point scale, higher indicates worse function

Functional Assessments

Activities of Daily Living:

ADCS-ADL: Alzheimer's Disease Cooperative Study Activities of Daily Living
FAQ (Functional Activities Questionnaire): Caregiver-reported function
BADLS (Bristol Activities of Daily Living Scale)

Behavioral Measures

Neuropsychiatric Symptoms:

NPI (Neuropsychiatric Inventory): Caregiver-reported behavioral changes
CMAI (Cohen-Mansfield Agitation Inventory): Agitation assessment
Geriatric Depression Scale: Mood assessment

Competitive Landscape

Phase 2/3 Amyloid-Targeting Programs

| Drug | Company | Mechanism | Status |
|------|---------|-----------|--------|
| Lecanemab | Biogen/Eisai | Anti-Aβ protofibrils | Approved |
| Donanemab | Lilly | Anti-Aβ plaques | Approved |
| Remternetug | Lilly | Anti-Aβ | Phase 2/3 |
| AC-003 | Apollo | Anti-Aβ | Phase 2 |

Tau-Targeting Programs

| Drug | Company | Mechanism | Status |
|------|---------|-----------|--------|
| E2814 | Eisai/WashU | Anti-tau antibody | Phase 2/3 |
| BIIB080 | Biogen/Ionis | MAPT ASO | Phase 2 |
| NIO752 | Roche | MAPT ASO | Phase 1 |
| JNJ-63742057 | Janssen | Anti-tau antibody | Phase 1 |

Neuroprotection and Disease Modification

| Drug | Company | Mechanism | Status |
|------|---------|-----------|--------|
| Suvvy-101 | SuVvie | Neuroprotection | Phase 2 |
| GV971 | Green Valley | Multi-target | Phase 3 |

Trial Site Considerations

Global Distribution

Phase 2 trials typically involve multiple regions:

North America: United States and Canada - Major academic medical centers and specialized AD research sites

Europe: UK, Germany (Charité), France (INSERM), Spain - NIHR dementia research network and specialized sites

Asia-Pacific: Japan (J-ADNI network), South Korea, Australia (AIBL), Singapore - National Neuroscience Institute

Site Selection Criteria

Experience: Prior AD trial participation
Infrastructure: MRI, PET, CSF collection capabilities
Patient Access: Diverse patient population
Regulatory: Track record with local authorities

Safety Monitoring

Adverse Event Categories

Common Expected Events:

Injection site reactions (for parenteral therapies)
Headache
Fatigue
Upper respiratory infections

Special Safety Monitoring:

ARIA-E: Amyloid-related imaging abnormalities - edema
MRI monitoring required
Symptomatic management when needed
ARIA-H: Microhemorrhages or siderosis
Gradient echo MRI monitoring
Risk factors include anticoagulation, cerebral amyloid angiopathy

Laboratory Monitoring

Hematology: CBC with differential
Chemistry: Comprehensive metabolic panel
Urinalysis: Kidney function
CSF analysis: For intrathecal therapies

Statistical Considerations

Sample Size and Power

The 416 participants provide adequate power for:

Detecting moderate effect sizes (0.3-0.5 SD)
Multiple dose arms
Subgroup analyses

Statistical Analyses

Primary: Mixed model repeated measures (MMRM)
Sensitivity: Multiple imputation for missing data
Subgroup: Pre-specified demographic and biomarker subgroups
Multiplicity: Control for multiple endpoints and doses

Future Implications

If Successful

Advancement to Phase 3 pivotal trials
Potential breakthrough therapy designation
Integration with Biogen's broader AD portfolio
Competitive positioning against Lilly and Eisai

If Unsuccessful

Iterative study design modifications
Biomarker refinements
Combination approach exploration
Portfolio prioritization decisions

Patient Perspective

Trial Experience

Participants in this trial can expect:

Screening: 4-8 weeks of assessments

Baseline: Comprehensive biomarker and cognitive testing

Treatment: Regular infusions/injections per protocol

Monitoring: Frequent safety assessments and visits

Follow-up: Post-treatment observation period

Benefits and Risks

Potential Benefits:

Access to cutting-edge therapy
Regular medical monitoring
Contribution to scientific knowledge
Potential for direct therapeutic benefit

Potential Risks:

Treatment side effects
Placebo assignment (50% chance)
Time commitment
Trial procedures burden

Summary

This Phase 2 trial represents Biogen's strategic approach to developing next-generation Alzheimer's disease therapeutics. With 416 participants and a focus on biomarker-driven patient selection, the trial incorporates modern clinical trial design principles learned from previous amyloid-targeting programs. The results will inform not only Biogen's pipeline but also the broader field's understanding of optimal AD therapeutic development [1][2].

References

[ClinicalTrials.gov - NCT05399888](https://clinicaltrials.gov/study/NCT05399888)

[Biogen Alzheimer's Disease Pipeline](https://www.biogen.com/en/science-and-pipeline/alzheimers-disease)

[Leqembi FDA Approval](https://www.fda.gov/drugs/fda-approves-leqembi-treatment-alzheimers-disease)

[BIIB080 Phase 1 Study - Nature Medicine](https://doi.org/10.1038/s41591-024-03123-y)

[CLARITY-AD Phase 3 Results - Alzheimer's Disease](https://pubmed.ncbi.nlm.nih.gov/37444252/)

[Dononemab TRAILBLAZER-ALZ 2 Results](https://pubmed.ncbi.nlm.nih.gov/37336015/)

[FDA Approves First Drug for Imaging Amyloid Plaque](https://www.fda.gov/drugs/fda-approves-first-drug-imaging-amyloid-plaque-alzheimers-disease)

[FDA Approves Drug for Imaging Tau Pathology](https://www.fda.gov/drugs/fda-approves-drug-imaging-tau-pathology-alzheimers-disease)

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📗 Cite This Artifact

Biogen Alzheimer's Disease Phase 2 Trial (NCT05399888)

Overview

Trial Details

Background and Rationale

Overview

Trial Details

Background and Rationale

Trial Design

Study Type

Treatment Arms

Duration

Inclusion Criteria

Key Eligibility Requirements

Exclusion Criteria

Outcome Measures

Primary Endpoints

Secondary Endpoints

Exploratory Endpoints

Biogen AD Pipeline Overview

Approved Therapies

Clinical Development

Research Programs

Amyloid-Targeting Field Context

Scientific Rationale

Regulatory Context

Biomarker Considerations in AD Trials

Amyloid Biomarkers

Tau Biomarkers

Neurodegeneration Markers

Clinical Outcome Measures

Cognitive Assessments

Functional Assessments

Behavioral Measures

Competitive Landscape

Phase 2/3 Amyloid-Targeting Programs

Tau-Targeting Programs

Neuroprotection and Disease Modification

Trial Site Considerations

Global Distribution

Site Selection Criteria

Safety Monitoring

Adverse Event Categories

Laboratory Monitoring

Statistical Considerations

Sample Size and Power

Statistical Analyses

Future Implications

If Successful

If Unsuccessful

Patient Perspective

Trial Experience

Benefits and Risks

Summary

References

See Also

💬 Discussion