Latozinemab Continuation for Neurodegenerative Disease

Enrolling by invitation at 24 trial locations

Overseen By Helene Favre

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alector Inc.

Must be taking: Latozinemab

Disqualifiers: Heart disease, Liver disease, Kidney disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: Up to 190 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial continues to provide the drug latozinemab to individuals who participated in a previous study with this treatment. It focuses on those with neurodegenerative diseases, where nerve cells in the brain or spinal cord gradually lose function. Participants will receive latozinemab through an IV infusion every four weeks. Eligible individuals must have completed a prior latozinemab study and should not have severe allergies or major heart, liver, or kidney issues. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that latozinemab is likely to be safe for humans?

Research has shown that latozinemab has been safe in past studies. In one study, researchers found no major safety issues. Most participants did not experience serious side effects, indicating the treatment was well-tolerated. Earlier trials also demonstrated that latozinemab can increase certain protein levels in the brain, which suggests potential effectiveness.

However, individuals with severe allergies to certain proteins should exercise caution. Overall, current data suggests that latozinemab is generally safe for humans, but ongoing studies continue to assess long-term effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Latozinemab is unique because it targets a specific protein called progranulin, which is involved in neuroinflammation and cell survival. Unlike many current treatments for neurodegenerative diseases that primarily focus on managing symptoms, Latozinemab aims to alter the disease process itself. Researchers are excited about its potential to slow down or even halt the progression of these conditions, offering hope for more effective long-term management.

What evidence suggests that latozinemab might be an effective treatment for neurodegenerative disease?

Research has shown that latozinemab has not been effective for treating neurodegenerative diseases in past studies. In the INFRONT-3 trial, the treatment did not improve the main health outcomes. Although it increased levels of a protein called progranulin, this did not result in noticeable benefits for patients. The researchers are still analyzing the data, but current evidence does not support its effectiveness in improving symptoms of neurodegenerative conditions. This information enhances understanding of the disease, but suggests that latozinemab may not provide the improvement patients seek. ^{1 2 4 6 7}

Who Is on the Research Team?

Study Lead

Principal Investigator

Alector Inc.

Are You a Good Fit for This Trial?

This trial is for people who have already been in a Latozinemab study. They must be able to give consent, not pregnant or breastfeeding, and willing to use contraception. People with severe allergies to certain proteins, significant heart, liver or kidney disease, brain diseases other than FTD, or those on immunosuppressive therapy can't join.

Inclusion Criteria

Written informed consent must be obtained and documented (from the participant or, where jurisdictions allow it, from their legal decision maker)

You have finished taking part in the previous Latozinemab study.

I am not pregnant or breastfeeding.

Exclusion Criteria

Use of any experimental vaccine or gene therapy

You have had serious allergic reactions to certain types of medications made from proteins.

I do not have serious heart, liver, or kidney disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label latozinemab at a dose of 60 mg/kg every 4 weeks

Up to 190 weeks

Visits every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Latozinemab

Trial Overview The trial provides continued access to Latozinemab for participants from previous studies of the drug. It's designed to see if ongoing treatment remains safe and effective over a longer period.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 1 Intervention

Latozinemab (AL001) administered by IV infusion over 60 minutes, q4w

Who Is Running the Clinical Trial?

Alector Inc.

Lead Sponsor

Trials

11

Recruited

1,300+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a study of 497 elderly patients with inflammatory bowel disease, those treated with vedolizumab (VDZ) had a lower incidence of mild infections (93.1 per 1000 patient-years) compared to those on 5-aminosalicylic acid (5-ASA) and chronic steroids, suggesting a potentially safer profile for VDZ.

The incidence of malignancies was similar between the VDZ and 5-ASA groups (17.6 vs. 15.6 per 1000 patient-years), while the steroid group had a higher incidence (42.6 per 1000 patient-years), indicating that VDZ may be a safer option for elderly patients with IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Infections and Malignancy Among Elderly Male Patients with IBD Exposed to Vedolizumab, Prednisone, and 5-ASA Medications: A Nationwide Retrospective Cohort Study. Khan, N., Pernes, T., Weiss, A., et al.[2021]

In a phase 2 trial involving 431 patients with mild to moderate Alzheimer's disease, crenezumab did not meet the primary efficacy endpoints for improving cognitive function over 68 weeks, indicating it may not significantly enhance cognition or function overall.

However, an exploratory analysis suggested that high-dose crenezumab may reduce cognitive decline in patients with milder forms of Alzheimer's, particularly those with Mini-Mental State Examination scores of 22 to 26, warranting further investigation into higher doses for early-stage patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ABBY: A phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease. Cummings, JL., Cohen, S., van Dyck, CH., et al.[2022]

Rituximab (RTX) has a relatively low incidence of adverse events (AEs) in patients with neuromyelitis optica spectrum disorder (NMOSD), with 28.57% of patients experiencing any AEs, and most being mild to moderate in severity.

Compared to other immunosuppressants like azathioprine and mycophenolate mofetil, RTX appears to be safer, making it a recommended first-line treatment for NMOSD due to its favorable safety profile and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of rituximab in neuromyelitis optica spectrum disorder: a systematic review and meta-analysis. Wang, H., Zhou, J., Li, Y., et al.[2022]

A review of 31 immunomodulatory drugs approved between 1998 and 2017 revealed 372 postmarketing safety-related label modifications, indicating that safety issues are often identified after a drug is on the market, with a median duration of 5 years before these issues are recognized.

The most common safety concerns were related to infections and immunologic phenomena, and drugs approved through expedited pathways had more safety issues compared to those approved through regular processes, highlighting the need for ongoing monitoring of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twenty Years of Targeted and Biologic Immunomodulatory Drugs: Postmarketing Modifications of Drug Labels Approved by the US Food and Drug Administration. Berman, J., Yavne, Y., Edel, Y., et al.[2022]

In a study of 1000 patients with multiple sclerosis (MS) and related disorders treated with rituximab, the rates of serious safety events (SSEs) such as infections and lymphopenia were found to be relatively low, with specific incidence rates per 1000 person-years for lymphopenia at 19.2 and infections at 38.6.

Risk factors for infections included longer duration of therapy, male gender, increased disability, and prior immunosuppression, highlighting the importance of careful monitoring and risk assessment in patients undergoing B-cell depleting therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious safety events in rituximab-treated multiple sclerosis and related disorders. Vollmer, BL., Wallach, AI., Corboy, JR., et al.[2021]

Citations

1. investors.alector.com investors.alector.com/news-releases/news-release-details/alector-announces-topline-results-latozinemab-phase-3-trial

Press Release “While latozinemab did not demonstrate a clinical benefit in INFRONT-3, the insights gained are invaluable for understanding progranulin-related ...

2. theaftd.org theaftd.org/posts/front-page/alector-therapeutics-announced-results-from-their-phase-3-clinical-trial-evaluating-latozinemab/

Alector Therapeutics Announces Results From Their Phase ... While latozinemab did result in elevations in progranulin, the treatment did not result in changes in this primary clinical outcome measure, nor ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06111014?intr=AL001&aggFilters=phase:3&rank=2

NCT06111014 | Continuation Study for Latozinemab A Continuation Study of Latozinemab in Participants With Neurodegenerative Disease. Conditions. Neurodegenerative Diseases. Neurodegenerative Diseases.

4. drugs.com drugs.com/clinical_trials/alector-announces-topline-results-latozinemab-phase-3-trial-individuals-frontotemporal-dementia-due-22214.html

Alector Announces Topline Results from Latozinemab ... More in-depth analysis of the data is ongoing. “While latozinemab did not demonstrate a clinical benefit in INFRONT-3, the insights gained are ...

5. biospace.com biospace.com/drug-development/alector-scraps-dementia-drug-after-phase-iii-flop-lays-off-49-of-staff

Alector Scraps Dementia Drug After Phase III Flop, Lays Off ... The decision follows disappointing late-stage data from the Phase III INFRONT-3 trial, which found no clinical benefit to latozinemab treatment ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10865485/

Phase 1 study of latozinemab in progranulin‐associated ... Latozinemab demonstrated a favorable safety profile in a phase 1 clinical trial. Latozinemab increased PGRN levels in the CNS of symptomatic FTD‐GRN ...

7. clinicaltrials.eu clinicaltrials.eu/inn/latozinemab/

Latozinemab – Application in Therapy and Current Clinical ... This comprehensive safety monitoring will help researchers better understand the long-term effects and tolerability of Latozinemab in patients with ...