galcanezumab-ad-nct07323927

Galcanezumab AD (NCT07323927)

Overview

The Galcanezumab AD trial (NCT07323927) is an investigator-initiated Phase 1 clinical study evaluating the efficacy and safety of galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide (CGRP), in patients with mild-to-moderate Alzheimer's disease. This trial is conducted by Xuanwu Hospital, Capital Medical University in Beijing, China["@clinicaltrialsgov2026"].

Galcanezumab AD (NCT07323927)

Overview

The Galcanezumab AD trial (NCT07323927) is an investigator-initiated Phase 1 clinical study evaluating the efficacy and safety of galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide (CGRP), in patients with mild-to-moderate Alzheimer's disease. This trial is conducted by Xuanwu Hospital, Capital Medical University in Beijing, China["@clinicaltrialsgov2026"].

Galcanezumab (brand name Emgality) is already approved for migraine prevention. This trial explores whether CGRP modulation may provide cognitive benefits in Alzheimer's disease, based on emerging evidence that CGRP plays complex roles in both neuroprotection and pathological processes in the brain.

Trial Identifier: NCT07323927 Status: Recruiting (as of March 2026) Start Date: August 2025 Estimated Completion: March 2027 Phase: Early Phase 1 Enrollment: 10 participants Sponsor: Xuanwu Hospital, Capital Medical University

Rationale: CGRP in Alzheimer's Disease

The CGRP Paradox

Calcitonin gene-related peptide (CGRP) is a neuropeptide with complex, sometimes paradoxical effects in the nervous system. While initially studied in the context of migraine pathophysiology, emerging research suggests CGRP may play important roles in both normal cognitive function and neurodegenerative processes[@cgrp_ad][@cgrp_neuro]:

Potential Protective Effects:

• Promotes neurogenesis in the hippocampus
• Modulates synaptic plasticity and memory formation
• Exhibits anti-inflammatory properties in some contexts
• May protect against excitotoxicity

• Elevated CGRP may contribute to vascular dysfunction
• Can promote neuroinflammation in certain conditions
• May interact with amyloid and tau pathology

Epidemiological Link to Migraine

Epidemiological studies have revealed interesting associations between migraine and Alzheimer's disease:

• Some studies suggest migraine may be a risk factor for dementia
• Shared pathways involving CGRP, neuroinflammation, and vascular function
• Common comorbidities affecting quality of life in both conditions[@migraine_ad]

Trial Design

Study Type

Design: Single-arm, open-label, Phase 1 clinical trial

Allocation: All participants receive galcanezumab (no placebo control)

Duration: 24 weeks of treatment with 12-week follow-up (36 weeks total)

Treatment Regimen

| Phase | Dose | Administration |
|-------|------|----------------|
| Loading | 240 mg | Single subcutaneous injection at baseline |
| Maintenance | 120 mg | Every 4 weeks (weeks 4, 8, 12, 16, 20, 24) |

Total: 6 doses over 24 weeks

Assessment Schedule

| Visit | Timepoint | Assessments |
|-------|-----------|-------------|
| Visit 1 (Screening) | Week -4 to 0 | Eligibility verification, baseline cognitive testing |
| Visit 2 (Baseline) | Week 0 | Pre-treatment assessments, first dose administration |
| Visit 3 | Week 12 | Mid-treatment cognitive assessment |
| Visit 4 | Week 24 | End-of-treatment assessment |
| Visit 5 | Week 36 | 12-week post-treatment follow-up |

Endpoints

Primary Endpoint

CGRP Levels in Cerebrospinal Fluid and Plasma

• Measure CGRP levels in CSF and plasma at baseline and week 24
• Assess whether galcanezumab treatment affects CGRP levels in the CNS

Secondary Endpoints

Cognitive Measures:

• ADAS-Cog (Alzheimer's Disease Assessment Scale - Cognitive Subscale) at baseline, weeks 12, 24, and 36
• MMSE (Mini-Mental State Examination) at baseline, weeks 12, 24, and 36
• CDR-SB (Clinical Dementia Rating - Sum of Boxes) at baseline, weeks 12, 24, and 36

• ADCS-CGIC (Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change)
• ADCS-ADL (Alzheimer's Disease Cooperative Study - Activities of Daily Living)
• NPI (Neuropsychiatric Inventory)

• Adverse events (AEs)
• Serious adverse events (SAEs)
• Vital signs and laboratory values
• Hamilton Depression Scale (HAMD)

Exploratory Endpoints

• Resting-state functional MRI (rs-fMRI) with amplitude of low-frequency fluctuations (ALFF) at baseline and week 24

Eligibility Criteria

Inclusion Criteria

• Age 50-90 years at enrollment
• Meeting NIA-AA core clinical criteria for probable Alzheimer's disease
• CDR global score 1-2; CDR memory box score ≥0.5
• Confirmed amyloid positivity (PET or CSF biomarkers)
• MMSE score 12-26 at screening
• At least 4-6 years of formal education
• Stable medication regimen for ≥3 months prior to study
• Available caregiver (≥8 hours/week with participant)
• Provision of informed consent

Exclusion Criteria

• Neuropsychiatric symptoms outside typical AD spectrum
• TIA, stroke, or seizure within past 12 months
• Known allergy to galcanezumab or monoclonal antibodies
• Cardiovascular disease (severe arrhythmias, uncontrolled hypertension)
• Gastrointestinal diseases (active peptic ulcer, inflammatory bowel disease)
• MRI contraindications (pacemaker, ferromagnetic implants)
• MRI evidence of other significant lesions
• Current participation in other AD clinical trials
• Unstable medical conditions

Significance

This pilot study represents an exploratory investigation into CGRP modulation as a potential AD therapeutic approach. While the sample size is small (n=10), the comprehensive biomarker and imaging assessments may provide valuable mechanistic insights:

Results from this trial may inform future Phase 2/3 studies if positive signals are observed.

Cross-References

• [CGRP Pathway](/mechanisms/cgrp-pathway) — Mechanism overview
• [Alzheimer's Disease](/diseases/alzheimers-disease) — Disease context
• [Xuanwu Hospital](/institutions/xuanwu-hospital-capital-medical-university) — Trial site

References