Alpha-1 MP for Emphysema Due to AATD

(SPARTA Trial)

Recruiting at 52 trial locations

Overseen By Gordon McAlester

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Grifols Therapeutics LLC

Must not be taking: Systemic steroids, Antibiotics

Disqualifiers: Lung transplant, Lung surgery, Smoking, others

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: 160

Duration: 156 weeks

345 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if Alpha-1 MP, given through an IV drip regularly, can improve lung health in patients with lung conditions. The effectiveness will be monitored using CT scans over a long period. Alpha-1 MP is related to a therapy that has been used to reduce severe lung issues in patients.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have used certain treatments like alpha1-PI therapy or high-dose steroids recently. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Alpha-1 MP for emphysema due to AATD?

Research shows that long-term treatment with intravenous alpha-1 antitrypsin (a protein that protects the lungs) is safe and can slow down the decline in lung function in patients with severe alpha-1 antitrypsin deficiency and emphysema. ^{1 2 3 4 5}

Is Alpha-1 MP safe for humans?

Alpha-1 MP, used for treating alpha1-antitrypsin deficiency, has been shown to be generally safe and well-tolerated in both Japanese and non-Japanese patients, with few adverse reactions reported during long-term use. ^{2 6 7 8 9}

How is the drug Alpha-1 MP different from other treatments for emphysema due to AATD?

Alpha-1 MP is unique because it is specifically designed to address the deficiency of alpha-1 antitrypsin, a protein that protects the lungs from damage. This drug works by augmenting (increasing) the levels of this protein in the body, which is different from other treatments that may not target the underlying cause of the deficiency. ^{4 10 11 12 13}

Eligibility Criteria

This trial is for individuals with a specific lung condition called Alpha-1 Antitrypsin Deficiency (AATD) and related emphysema. Participants must have certain levels of lung function, documented AATD genetic variants, and evidence of emphysema. Smokers or those who've had recent alpha1-PI therapy, lung surgery, severe allergic reactions to blood products, or exacerbations of COPD are excluded.

Inclusion Criteria

Your blood test shows that you have low levels of alpha1-PI.

Your lung function test shows very low carbon monoxide diffusion or signs of lung damage on a recent CT scan.

My lung function test shows moderate to severe COPD.

Exclusion Criteria

I have been on alpha1-PI therapy for over a month in the last six months.

I have had a worsening of my COPD within the last 5 weeks.

I have not had lung surgery in the last 2 years, except for a biopsy.

Timeline

Pre-screening

Optional pre-screening phase to identify potential participants

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly IV infusions of Alpha-1 MP or placebo for 156 weeks

156 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

End of Study Visit at Week 160

Treatment Details

Interventions

• Alpha-1 MP

Trial Overview The study tests two doses (60 mg/kg and 120 mg/kg) of a drug called Alpha-1 MP against a saline placebo. Given weekly through IV for three years, the effectiveness is measured by CT scans of the lungs. The trial randomly assigns participants to receive either dose or placebo without them knowing which one they're getting.

Participant Groups

Group I: Alpha-1 MP 60 mg/kg Experimental Treatment 1 Intervention

Alpha-1 MP 60 mg/kg administered weekly by IV infusion for 156 weeks

Group II: Alpha-1 MP 120 mg/kg Experimental Treatment 1 Intervention

Alpha-1 MP 120 mg/kg administered weekly by IV infusion for 156 weeks

Group III: Placebo Placebo Group 1 Intervention

0.9% Sodium Chloride for Injection, USP, administered weekly by IV infusion for 156 weeks

Who Is Running the Clinical Trial?

Grifols Therapeutics LLC

Lead Sponsor

Trials

59

Recruited

6,000+

Findings from Research

Long-term intravenous augmentation therapy with alpha 1-antitrypsin (alpha 1-AT) is safe and well-tolerated in 443 patients with severe alpha 1-AT deficiency and pulmonary emphysema, with few adverse reactions reported.

The therapy appears to slow the decline in lung function, as indicated by a measured decline in forced expiratory volume in 1 second (delta FEV1) of 57.1 ml per year, which varies based on the patient's initial lung function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term therapy of alpha 1-antitrypsin-deficiency-associated pulmonary emphysema with human alpha 1-antitrypsin]. Wencker, M., Banik, N., Buhl, R., et al.[2009]

Alpha 1-antitrypsin (AAT) augmentation therapy has shown promising efficacy in treating conditions beyond pulmonary emphysema, such as fibromyalgia, systemic vasculitis, and bronchial asthma, based on ten case reports and two clinical trials.

Despite being primarily approved for severe AAT deficiency-related pulmonary emphysema, the therapy has demonstrated success in patients where conventional treatments failed, indicating a need for further research to confirm its safety and efficacy in these other conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema. Blanco, I., Lara, B., de Serres, F.[2021]

Long-term intravenous augmentation therapy with alpha1-antitrypsin is feasible and safe for patients with severe alpha1-antitrypsin deficiency, as shown in a study of 443 patients with few adverse reactions.

The study found that the decline in lung function (measured by forced expiratory volume in one second) was related to the initial lung function levels, indicating that while therapy is beneficial, the rate of decline varies based on the severity of the disease at baseline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment of alpha1-antitrypsin deficiency-related pulmonary emphysema with human alpha1-antitrypsin. Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL)-alpha1-AT-study group. Wencker, M., Banik, N., Buhl, R., et al.[2019]

In a long-term study involving four Japanese patients with alpha1-antitrypsin deficiency, weekly intravenous infusions of 60 mg/kg Alpha-1 MP were found to be generally safe and well-tolerated over a period of 52 weeks, with most reported adverse events being mild.

The treatment did not lead to significant changes in pulmonary function tests or laboratory parameters, indicating that Alpha-1 MP does not adversely affect lung function or overall health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of Prolastin®-C, an alpha1-proteinase inhibitor, in Japanese patients with alpha1-antitrypsin deficiency. Seyama, K., Suzuki, M., Tasaka, S., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Long-term evolution of lung function in individuals with alpha-1 antitrypsin deficiency from the Spanish registry (REDAAT). [2018]

2. Germany pubmed.ncbi.nlm.nih.gov

[Long-term therapy of alpha 1-antitrypsin-deficiency-associated pulmonary emphysema with human alpha 1-antitrypsin]. [2009]

3. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life in patients with alpha-1 antitrypsin deficiency: the French experience. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Exacerbations in subjects with alpha-1 antitrypsin deficiency receiving augmentation therapy. [2009]

6. England pubmed.ncbi.nlm.nih.gov

Long-term treatment of alpha1-antitrypsin deficiency-related pulmonary emphysema with human alpha1-antitrypsin. Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL)-alpha1-AT-study group. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term safety of Prolastin®-C, an alpha1-proteinase inhibitor, in Japanese patients with alpha1-antitrypsin deficiency. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of Alpha-1 MP (Prolastin®-C) in Japanese patients with alpha1-antitrypsin (AAT) deficiency. [2022]

9. England pubmed.ncbi.nlm.nih.gov

A review of augmentation therapy for alpha-1 antitrypsin deficiency. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Matrix metalloprotease polymorphisms are associated with gas transfer in alpha 1 antitrypsin deficiency. [2009]

12. England pubmed.ncbi.nlm.nih.gov

Exacerbations and duration of smoking abstinence are associated with the annual loss of FEV1 in individuals with PiZZ alpha-1-antitrypsin deficiency. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Small airways disease in patients with alpha-1 antitrypsin deficiency. [2023]