Alpha-1 MP Safety for Alpha-1 Antitrypsin Deficiency

(SPARTA-OLE Trial)

Recruiting at 27 trial locations

Overseen By David Taylor

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Grifols Therapeutics LLC

Disqualifiers: Congestive heart failure, Liver cirrhosis, Pulmonary malignancy, Smoking, 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: 1

Duration: 104 weeks

290 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a 2-year open-label, multicenter extension of the double-blind, placebo-controlled GTi1201 study. The purpose of this study is to obtain an additional 2 years of safety data for intravenously administered Alpha1-MP 60 mg/kg/week in subjects with alpha1-antitrypsin deficiency (AATD).

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 study team or your doctor.

What data supports the effectiveness of the drug Alpha-1 MP for treating Alpha-1 Antitrypsin Deficiency?

Research shows that augmentation therapy with alpha1-antitrypsin, similar to Alpha-1 MP, is the only specific treatment for Alpha-1 Antitrypsin Deficiency and is generally well-tolerated, with some studies indicating it may help slow the decline in lung function. ^{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 safe and well-tolerated in both Japanese and non-Japanese patients, with few adverse reactions reported during long-term use. ^{1 2 4 6 7}

Eligibility Criteria

This trial is for individuals who have completed the GTi1201 study or shown a specific decline in lung function, and can consent to participate. It's not for those with certain metal implants, claustrophobia preventing CT scans, pregnant or non-contracepting women, smokers, substance abusers, other cancer patients with less than a year survival prediction, severe diseases like heart failure or liver cirrhosis, history of severe reactions to blood products, compliance issues with protocols or any condition that might risk their safety or skew results.

Inclusion Criteria

Is willing and able to provide informed consent

You have been in another study for a certain amount of time, or your lung function has declined at a specific rate in a previous study.

Exclusion Criteria

Is currently participating in another investigational product (IP) study.

I have a new metal object in my body that could affect chest CT scans.

I am not pregnant, breastfeeding, and if I can have children, I agree to use effective birth control during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive weekly intravenous infusions of Alpha-1 MP 60 mg/kg for 104 weeks

104 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Alpha-1 MP

Trial Overview The trial is testing the long-term safety of Alpha1-MP (a medication given through veins) at a dose of 60 mg/kg/week over two years in people with alpha-1 antitrypsin deficiency which can lead to conditions like emphysema.

Participant Groups

Group I: Alpha-1 MP Experimental Treatment 1 Intervention

Alpha-1 MP 60 mg/kg/week for up to 104 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]

Augmentation therapy with exogenous alpha1-antitrypsin significantly slows the decline in lung function (FEV1) by 23% in patients with alpha1-antitrypsin deficiency, based on a meta-analysis of five trials involving 1509 patients.

The most pronounced benefits were observed in patients with a baseline FEV1 between 30-65% of predicted, where the therapy resulted in a 26% reduction in the rate of decline, indicating that those with moderate obstruction are likely to benefit the most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentation therapy for alpha1 antitrypsin deficiency: a meta-analysis. Chapman, KR., Stockley, RA., Dawkins, C., 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]

In a long-term study of seven patients with Alpha-1-Antitrypsin Deficiency, weekly intravenous augmentation therapy significantly slowed the decline in lung function (FEV1) compared to the three years prior to the program, indicating its efficacy in managing COPD symptoms.

The home care program, 'Alpha-1-Mobile', was found to be safe and well-accepted, with minimal hospitalizations due to exacerbations and no adverse events related to the augmentation therapy, highlighting its practicality for ongoing patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Longterm Homecare Augmentation Program in Alpha-1-Antitrypsin Deficient Patients]. Wilke, A., Semper, H., Gross, C., 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Augmentation therapy for alpha1 antitrypsin deficiency: a meta-analysis. [2019]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

5. Germany pubmed.ncbi.nlm.nih.gov

[Longterm Homecare Augmentation Program in Alpha-1-Antitrypsin Deficient Patients]. [2022]

6. Spain pubmed.ncbi.nlm.nih.gov

[Replacement therapy of emphysema caused by alpha 1-antitrypsin deficiency]. [2006]

7. 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]