Pneumococcal Vaccine for Alpha-1 Antitrypsin Deficiency

(IgG in AATD Trial)

Overseen By David LaFon, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Alabama at Birmingham

Disqualifiers: Pneumococcal vaccine allergy, others

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

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

Compensation: Varies

Number of Visits: 3

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if individuals with a specific genetic mutation linked to alpha-1 antitrypsin deficiency (a lung condition) also have genetic changes that increase their susceptibility to infections. Researchers will compare immune responses to the 20-valent pneumococcal conjugate vaccine (PCV20), which protects against pneumonia, between two groups: those with no COPD flare-ups and those with two or more in the past year. Suitable candidates for the trial have one abnormal SERPINA1 gene, have experienced either none or at least two COPD exacerbations in the past year, and have not received a pneumococcal conjugate vaccine in the last five years. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for the 20-valent pneumococcal conjugate vaccine?

Research has shown that the 20-valent pneumococcal conjugate vaccine (PCV20) is generally safe. Studies found that infants tolerated PCV20 well, with side effects similar to the earlier PCV13 vaccine, indicating mild reactions comparable to existing vaccines. Another study confirmed that PCV20 has a safety profile and immune response similar to other approved pneumococcal vaccines, suggesting it works effectively and is unlikely to cause serious issues. While no treatment is without risks, the available data suggest that PCV20 is well-tolerated in humans. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for Alpha-1 Antitrypsin Deficiency aim at managing symptoms and preventing lung damage, often involving regular enzyme replacement therapies. However, the 20-valent pneumococcal conjugate vaccine (PCV20) is unique because it focuses on preventing pneumococcal infections, which can exacerbate lung issues in these patients. Researchers are excited about this vaccine because it covers 20 different strains of pneumococcal bacteria, offering broad protection that could reduce the frequency and severity of lung infections. This preventive approach could significantly improve quality of life and decrease healthcare needs for those with Alpha-1 Antitrypsin Deficiency.

What evidence suggests that the 20-valent pneumococcal conjugate vaccine might be an effective treatment for alpha-1 antitrypsin deficiency?

Studies have shown that the 20-valent pneumococcal conjugate vaccine (PCV20) strengthens the immune system against pneumococcal bacteria. This vaccine is approved for use in various age groups and effectively boosts the body's defenses. In this trial, participants who are heterozygous for the SERPINA1 'Z' allele will receive PCV20 to evaluate its effectiveness and safety in individuals with alpha-1 antitrypsin deficiency. Researchers are particularly interested in how genetic differences in people with this condition might affect their response to the vaccine. The vaccine is generally safe and well-tolerated, helping to prevent infections from pneumococcal bacteria, which can cause serious lung problems. Because it is approved and effective at preventing these infections, PCV20 is a promising choice for people with conditions that increase their risk of infection. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with Alpha-1 Antitrypsin Deficiency, which can lead to COPD and antibody deficiency. Participants should have a genetic mutation in the SERPINA1 gene and will be grouped based on their history of COPD exacerbations.

Inclusion Criteria

I have had either no or more than 2 COPD flare-ups in the last year.

I carry one copy of the SERPINA1 Z gene mutation.

I haven't had a pneumococcal conjugate vaccine in the last 5 years.

Exclusion Criteria

I have received a pneumococcal vaccine in the last 5 years.

Known allergy, severe adverse reaction, or other sensitivity to pneumococcal conjugate vaccines

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive the 20-valent pneumococcal conjugate vaccine (PCV20, Pfizer)

1 day

1 visit (in-person)

Follow-up

Participants are monitored for immune response and antibody levels post-vaccination

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 20-valent pneumococcal conjugate vaccine

Trial Overview The study tests how people with one abnormal copy of the SERPINA1 gene respond to the PCV20 vaccine by Pfizer. It aims to see if there's a link between this genetic variation and increased risk of respiratory infections.

How Is the Trial Designed?

Group I: SERPINA1 'Z' heterozygotes Experimental Treatment 1 Intervention

Participants who are heterozygous for the SERPINA1 'Z' allele with either 0 or 2+ exacerbations in the previous year, and have not received pneumococcal vaccination within 5 years will be given PCV20.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Alpha-1 Foundation

Collaborator

Trials

14

Recruited

19,700+

Citations

1. cdc.gov cdc.gov/acip/grade/pneumo-PCV20-age-based.html

GRADE: 20-valent pneumococcal conjugate vaccine ... A systematic literature search was completed to review all available evidence on the immunogenicity and safety of PCV15 and PCV20 among age groups for which the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12425875/

A Cost-Effectiveness Analysis of the Switch to 20-Valent ... The pneumococcal conjugate vaccine (PCV) with valency of 20 (PCV20) was approved for pediatric use by the European Commission in 2024.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07135427

Genetic Variation in IgG in Alpha 1 Antitrypsin Deficiency To investigate this hypothesis, we will compare immune responses to the 20-valent pneumococcal conjugate vaccine (PCV20, Pfizer) between participants who have ...

4. smartpatients.com smartpatients.com/trials/NCT07135427

Genetic Variation in IgG in Alpha 1 Antitrypsin Deficiency To investigate this hypothesis, we will compare immune responses to the 20-valent pneumococcal conjugate vaccine (PCV20, Pfizer) between participants who have ...

5. cdc.gov cdc.gov/acip/grade/pneumo-PCV20-risk-based.html

20-valent pneumococcal conjugate vaccine (PCV20) for ... A systematic literature search was completed to review all available evidence on the immunogenicity and safety of PCV15 and PCV20 among age ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34525007/

Safety and Immunogenicity of a 20-valent Pneumococcal ... Administration of PCV20 in US infants was well tolerated, with a safety profile similar to PCV13, and induced robust serotype-specific immune responses.

7. withpower.com withpower.com/trial/phase-4-alpha-1-antitrypsin-deficiency-8-2025-bec26

Pneumococcal Vaccine for Alpha-1 Antitrypsin Deficiency ... 20-valent pneumococcal conjugate vaccine will have tolerable side effects & efficacy for patients with Alpha-1 Antitrypsin Deficiency, Chronic Obstructive ...

8. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer-announces-top-line-results-phase-3-study-20-valent

Pfizer Announces Top-Line Results from Phase 3 Study ... 20-valent pneumococcal conjugate vaccine demonstrated comparable safety and immunogenicity profile to licensed pneumococcal vaccines.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8369947/

Heterozygosity of the Alpha 1‐Antitrypsin Pi*Z Allele and ... Z allele homozygosity (Pi*ZZ) is the most common cause of alpha 1‐antitrypsin deficiency and is a proven risk factor for cirrhosis. We examined whether ...