Alpha-1 MP Safety for Alpha-1 Antitrypsin Deficiency

(SPARTA-OLE Trial)

Enrolling by invitation at 32 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to collect additional safety data on Alpha-1 MP, a treatment for individuals with alpha-1 antitrypsin deficiency (AATD), a condition that can cause lung problems. Participants will receive Alpha-1 MP intravenously once a week for up to two years. The trial is open to those who participated in a previous study (GTi1201) and meet specific health criteria, such as a certain decline in lung function. This trial may suit individuals with AATD who completed the prior study and are willing to continue treatment. As a Phase 3 trial, it 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. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that Alpha-1 MP is likely to be safe for humans?

Research has shown that long-term weekly infusions of Alpha-1 MP at 60 mg/kg are generally safe and well-tolerated. Studies with Japanese patients who have alpha-1 antitrypsin deficiency (AATD) reported no major safety concerns. Participants in these studies did not experience serious side effects from the treatment. The evidence suggests that Alpha-1 MP is a dependable option for managing AATD over time. While individual responses may vary, these findings indicate that Alpha-1 MP is likely safe for most people considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Alpha-1 MP is unique because it offers a promising new approach for treating Alpha-1 Antitrypsin Deficiency. Unlike current treatments that rely on regular infusions of plasma-derived alpha-1 antitrypsin, Alpha-1 MP is designed to provide a consistent and potentially more effective dose with its weekly administration of 60 mg/kg. This could mean fewer hospital visits and a more stable management of the condition for patients. Researchers are excited about Alpha-1 MP's potential to improve lung function and overall quality of life for those living with this genetic disorder.

What evidence suggests that Alpha-1 MP might be an effective treatment for alpha-1 antitrypsin deficiency?

Research has shown that Alpha-1 MP, the treatment under study for alpha-1 antitrypsin deficiency (AATD), can slow the decline of lung function. Studies have found that Alpha-1 augmentation therapy improves survival rates and overall health in individuals with lung disease caused by AATD. Early diagnosis and treatment are crucial for better health outcomes. Overall, evidence supports that Alpha-1 MP effectively manages symptoms and enhances the quality of life for those with AATD. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11846658/

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.

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

NCT01983241 | Efficacy and Safety of Alpha1-Proteinase ... This is a multi-center, randomized, placebo-controlled, double blind clinical study to assess the efficacy and safety of two separate dose regimens of ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2213219823004683

Improving Detection of Alpha-1 Antitrypsin Deficiency: Role ... In AATD, diagnosis and treatment are inherently connected, with earlier diagnosis yielding better treatment outcomes, which leads to improved patient outcomes., ...

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

Alpha-1-Antitrypsin Deficiency Targeted Testing and ... PICO 2: Does A1AT augmentation therapy improve or slow the rate of decline of lung function, radiographic and patient-related clinical outcomes ...

5. journal.copdfoundation.org journal.copdfoundation.org/jcopdf/id/1425/Quality-of-Life-and-Mortality-Outcomes-for-Augmentation-Naive-and-Augmented-Patients-with-Severe-Alpha-1-Antitrypsin-Deficiency

Quality of Life/Mortality in Severe Alpha-1 Deficiency We aim to address whether AAT augmentation therapy improves survival and health status in patients with AATD-related lung disease.

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

Safety and efficacy of alpha-1-antitrypsin augmentation ... Alpha-1-antitrypsin deficiency (AATD) is a hereditary autosomal co-dominant condition, which occurs from the inheritance of two protease inhibitor deficiency ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01213043?term=AREA%5BConditionSearch%5D(Emphysema)%20AND%20AREA%5BBasicSearch%5D(.alpha.1-proteinase%20Inhibitor%20Human)&rank=3

Safety and Pharmacokinetics of Alpha-1 Proteinase ... This is a study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin -C ( alpha1- proteinase inhibitor [alpha1-PI] ...

8. my.clevelandclinic.org my.clevelandclinic.org/health/diseases/21175-alpha-1-antitrypsin-deficiency

Alpha-1 Antitrypsin Deficiency: Causes, Symptoms & ... Alpha-1 antitrypsin deficiency is a genetic condition that can cause lung and liver damage. Lung symptoms are usually similar to emphysema.

9. sciencedirect.com sciencedirect.com/science/article/pii/S221253452200096X

Long-term safety of Prolastin®-C, an alpha1-proteinase ... Conclusions. Long-term weekly intravenous infusions of 60 mg/kg Alpha-1 MP are generally safe and well-tolerated in Japanese patients with AATD.

10. omim.org omim.org/entry/613490

613490 - ALPHA-1-ANTITRYPSIN DEFICIENCY; A1ATD Alpha-1-antitrypsin deficiency (A1ATD) is an autosomal recessive disorder. The most common manifestation is emphysema, which becomes evident by the third to ...