Alpha-1 MP for Emphysema Due to AATD

(SPARTA Trial)

Not currently recruiting at 63 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Alpha-1 MP, an intravenous therapy, to determine its effectiveness for emphysema caused by Alpha-1 Antitrypsin Deficiency (AATD). Researchers will compare two doses of Alpha-1 MP, administered weekly by IV, to a placebo over three years. The goal is to assess whether Alpha-1 MP can improve lung health, as observed on CT scans. Suitable participants have been diagnosed with AATD and show signs of emphysema. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Alpha-1 MP, a treatment for alpha-1 antitrypsin deficiency (AATD), is generally safe. Studies have found that when administered intravenously, it is usually well-tolerated. Side effects are uncommon and typically mild if they occur. Although Alpha-1 MP is not yet approved for all conditions, evidence from past patient experiences suggests its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Alpha-1 MP for emphysema due to Alpha-1 Antitrypsin Deficiency (AATD) because it offers a targeted approach by using a protein replacement therapy. Unlike standard treatments, which often focus on relieving symptoms, Alpha-1 MP works by replacing the missing or deficient alpha-1 antitrypsin protein, potentially addressing the root cause of the condition. With weekly IV infusions, it aims to maintain adequate protein levels in the body, offering a more direct and potentially more effective treatment option for patients with AATD-related emphysema.

What evidence suggests that this trial's treatments could be effective for emphysema due to AATD?

Research shows that Alpha-1 MP, a treatment for emphysema caused by Alpha-1 Antitrypsin Deficiency (AATD), holds promise. Studies have found that Alpha-1 MP can extend patients' lives and slow the decline of lung function. This treatment adds the missing protein that protects the lungs, reducing damage over time. In this trial, participants will receive either Alpha-1 MP at a dose of 60 mg/kg or 120 mg/kg, or a placebo, to determine the most effective usage. Overall, evidence suggests it can improve the quality of life for people with emphysema related to AATD. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28558837/

Long-term clinical outcomes following treatment with alpha ... With the clinical efficacy of A1-PI therapy now demonstrated, further studies are required to assess long-term outcomes. Keywords: Alpha-1 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01983241

NCT01983241 | Efficacy and Safety of Alpha1-Proteinase ... The two Alpha-1 MP doses to be tested are 60 mg/kg and 120 mg/kg administered weekly by IV infusion for 156 weeks. The study consists of an optional pre- ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2844046/

Alpha1-Proteinase Inhibitor (Human) - PMC Additionally, Zemaira® proved equally effective at increasing serum AAT when compared to another human AAT. Survival and FEV1 Decline in Individuals with Severe ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024072141

Proteinase inhibitor (human) augmentation therapy for ... Assessing the efficacy of Alpha1-Proteinase inhibitor (human) augmentation therapy for Alpha1-Antitrypsin deficiency – Related emphysema: ...

5. respiratory-research.biomedcentral.com respiratory-research.biomedcentral.com/articles/10.1186/s12931-017-0574-1

Long-term clinical outcomes following treatment with alpha 1 ... Evidence is beginning to indicate an improvement in survival in patients with AATD receiving A1-PI therapy. It has also been suggested that a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2726081/

Safety and efficacy of alpha-1-antitrypsin augmentation ... Experience with intravenous augmentation therapy suggests that it is safe, with few and usually well tolerated side effects. The decision to initiate ...

7. jheor.org jheor.org/article/127446-clinical-and-economic-outcomes-in-patients-with-alpha-1-antitrypsin-deficiency-in-a-us-medicare-advantage-population

Clinical and Economic Outcomes in Patients With Alpha-1 ... Alpha-1 antitrypsin deficiency (AATD) testing rates and associated clinical and economic outcomes data in the US Medicare population are limited.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11846308/

Patient-centered assessment of treatment for alpha-1 ... Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that can result in a range of illnesses, with chronic obstructive pulmonary ...

9. journal.chestnet.org journal.chestnet.org/article/S0012-3692(24)05129-8/fulltext

Alpha-1-Antitrypsin Deficiency Targeted Testing and ... Alpha-1-antitrypsin (A1AT) deficiency is a common hereditary disorder associated with increased risk of developing chronic obstructive ...