#1 Clinical Trials Search in Europe

Alpha-1 antitrypsin deficiency – Trials in Disease

Go back

Ongoing Clinical Trials for Alpha-1 Antitrypsin Deficiency

There are currently 9 clinical trials studying new treatments for Alpha-1 Antitrypsin Deficiency, a genetic condition affecting the lungs and liver. These trials are testing various medications including inhaled therapies, gene-silencing treatments, gene therapy, and protein replacement options across multiple European countries.

Clinical trial locations

Study of inhaled alpha1-proteinase inhibitor (Kamada-AAT) in adults with alpha-1 antitrypsin deficiency and moderate to severe airflow limitation

This study is testing an inhaled medication called Kamada-AAT for Inhalation in adults with moderate to severe breathing difficulties. The medication contains human alpha1-proteinase inhibitor, a protein that helps protect lung tissue from damage.

Main inclusion criteria: Participants must be between 18 and 65 years old and have a confirmed diagnosis of severe deficiency with specific genetic types (Pi(ZZ), Pi(Z/Null), or Pi(Null/Null)). They must have moderate to severe breathing problems, with lung function tests showing FEV1 between 40% and 80% of normal and an FEV1/SVC ratio of 70% or less. Participants must either have never received augmentation therapy or stopped it at least 8 weeks before the study. Blood levels of alpha-1 antitrypsin must be 11 μM or lower.

Main exclusion criteria: People who have had severe lung infections requiring hospitalization in the past year or two or more moderate infections requiring treatment cannot participate. Current smokers or those who quit less than 6 months ago are excluded. The study also excludes people with a history of lung transplant, other serious lung diseases, allergic reactions to similar medications, or significant liver disease. Pregnant women or those planning to become pregnant during the study cannot take part.

Study focus: The main goal is to determine if inhaling 80 mg of Kamada-AAT daily can help improve lung function over a two-year period. The study will compare the medication to placebo and regularly measure lung function through breathing tests and CT scans. After the initial two years, participants can continue treatment for an additional two years, during which all participants will receive the active medication.

Investigational drug: Kamada-AAT for Inhalation is delivered using an eFlow Nebuliser System. This inhaled form of alpha-1 antitrypsin works by delivering the protective protein directly into the lungs to help slow down lung damage and maintain lung function.

Study on Fazirsiran for Patients with Alpha-1 Antitrypsin Deficiency Liver Disease and Mild Fibrosis

This trial is studying Fazirsiran (also known as TAK-999), a medication designed to target specific genes in the liver to help reduce damage caused by this genetic condition. The study focuses on people with mild liver scarring.

Main inclusion criteria: Participants must be between 18 and 75 years old and have a confirmed diagnosis of the PiZZ genotype. They must have evidence of METAVIR stage 1 liver fibrosis confirmed by liver biopsy. Their lung health must meet specific protocol requirements.

Main exclusion criteria: People with other serious liver diseases not related to the deficiency, those who have had a liver transplant, or those with severe lung diseases unrelated to the condition cannot participate. The study also excludes people currently in another clinical trial, those with a history of drug or alcohol abuse, pregnant or breastfeeding women, and anyone with conditions that the study doctors believe would make participation unsafe.

Study focus: The main goal is to evaluate the long-term safety of Fazirsiran, with special focus on lung health. The study will monitor various health indicators including lung function and liver health over time to assess how the treatment affects these areas.

Investigational drug: Fazirsiran is administered as a subcutaneous injection, which means it is injected under the skin. This medication is designed to reduce the harmful proteins that accumulate in the liver, potentially improving liver function and slowing disease progression.

Study on Fazirsiran for Patients with Alpha-1 Antitrypsin Deficiency-Related Liver Disease and Fibrosis

This clinical trial is testing Fazirsiran (TAK-999) in people with more advanced liver disease. The study aims to evaluate how effective the medication is compared to placebo in improving liver health.

Main inclusion criteria: Participants of any sex must be between 18 and 75 years old with a confirmed diagnosis of the PiZZ genotype. They must have evidence of METAVIR stage F2, F3, or F4 liver fibrosis confirmed by a liver biopsy done during the screening period or within 6 months before joining the study. Their lung condition must meet specific criteria listed in the study protocol.

Main exclusion criteria: People with any other serious liver disease, those who have had a liver transplant, or those with a history of alcohol or drug abuse in the past year cannot participate. Pregnant or breastfeeding women, people currently in another clinical trial, those with a history of allergic reactions to the study medication, people with uncontrolled high blood pressure, active infections requiring treatment, or a history of cancer within the last five years (except certain skin cancers) are excluded.

Study focus: The study will evaluate changes in liver scarring over approximately 202 weeks (around 4 years). Participants will undergo liver biopsies at specific time points to assess the effectiveness of the treatment in reducing liver fibrosis and improving liver function. Regular assessments will include blood tests and imaging studies.

Investigational drug: Fazirsiran is administered through subcutaneous injections every four weeks. It works by targeting and reducing the abnormal protein that accumulates in the liver due to the deficiency, helping to prevent further liver damage.

Study on Long-Term Safety of Fazirsiran for Patients with Alpha-1 Antitrypsin Deficiency-Related Liver Disease

This is a long-term extension study evaluating the ongoing safety and effectiveness of Fazirsiran in people who have completed previous studies of this medication.

Main inclusion criteria: Participants must have previously participated in one of the earlier Fazirsiran studies (AROAAT2001 or AROAAT2002). Depending on which previous study and which cohort they were in, they can join this extension study at different time points after completing specific periods in those studies. If there is a delay of more than 24 weeks between the last dose in the previous study and the first dose in this extension, the situation should be discussed with the medical monitor. The study is open to participants of any gender.

Main exclusion criteria: People with a different liver disease not related to the deficiency, those not within the specified age range, those unable to follow study procedures, people with other serious health conditions that might interfere, pregnant or breastfeeding women, those participating in another clinical trial simultaneously, and people with a history of allergic reactions to similar medications are excluded.

Study focus: The study will monitor participants over an extended period, with regular follow-up visits scheduled every 12 weeks. The focus is on assessing the long-term safety and tolerability of Fazirsiran, with regular monitoring of vital signs, laboratory tests, and liver function.

Investigational drug: Fazirsiran continues to be administered through subcutaneous injections. The medication helps reduce the production of abnormal proteins that accumulate in the liver and cause damage, with the goal of managing liver disease over the long term.

Study on Long-Term Safety of INBRX-101 for Adults with Alpha-1 Antitrypsin Deficiency Emphysema

This study focuses on evaluating the long-term safety and tolerability of INBRX-101, a concentrate for solution for infusion, in adults with emphysema caused by the deficiency.

Main inclusion criteria: Participants must be between 18 and 80 years old with a confirmed diagnosis. They must show evidence of emphysema and have an FEV1 (a measure of lung function) that is 30% or more of the predicted value. For new patients in Cohort 1, the FEV1/FVC ratio must be less than 0.7 after using a bronchodilator. Participants must be current non-smokers.

Main exclusion criteria: People with a different lung condition other than emphysema caused by the deficiency cannot participate. Those not within the specified age range, unable to follow study procedures, with medical conditions that might interfere with the study or make it unsafe, pregnant or breastfeeding women, people currently in another clinical trial, those who recently had or are planning major surgery, people with a history of drug or alcohol abuse that might interfere with the study, or those with a known allergy to the study medication are excluded.

Study focus: The study aims to understand how well patients tolerate INBRX-101 over an extended period. It will track adverse events, monitor changes in lung density using CT scans, and examine how the body processes the treatment. The study will also assess whether any antibodies develop against the medication.

Investigational drug: INBRX-101 is administered intravenously at a dosage of 50mg/ml. It contains a special protein called human alpha-1-proteinase inhibitor immunoglobulin G fusion protein, designed to help manage emphysema symptoms by supplementing the deficient protein.

Study on the Safety and Effectiveness of BEAM-302 with MR0005 and GR0015 for Adults with Alpha-1 Antitrypsin Deficiency-Related Lung or Liver Disease

This clinical trial explores a new gene therapy treatment called BEAM-302, which is administered as a solution for injection through intravenous infusion. The study is divided into two phases: dose exploration and dose expansion.

Main inclusion criteria: Participants must be between 18 and 70 years old, able to understand the study and provide informed consent, and willing to avoid other experimental treatments during the study. They must have a confirmed diagnosis with the PiZZ genotype and show evidence of liver fibrosis at stages F1, F2, or F3 based on a liver biopsy or similar test within 6 months before joining. Lung function must show a postbronchodilator FEV1 of 40% or more of predicted value. Blood total alpha-1 antitrypsin levels must be less than 11 μM. Participants must have evidence of emphysema on CT scan or a DLCO (a test measuring lung gas transfer) of 70% or less of predicted value, and a FibroScan result of 12 kPa or less. They must be willing to avoid alcohol, herbal medications, daily NSAIDs, and strenuous exercise beyond their usual routine during the study. Both male and female participants must be willing to use highly effective contraception during specified periods. Total study participation is expected to last 15 years.

Main exclusion criteria: People with other serious health conditions that could interfere with the study, pregnant or breastfeeding women, those who participated in another clinical trial within the last 30 days, people with a history of allergic reactions to similar treatments, those unable to follow study procedures or attend required visits, people with a history of drug or alcohol abuse within the last year, those with unstable mental health conditions, people who have received an organ transplant, those with active infections requiring treatment, or a history of cancer within the last 5 years (except certain skin cancers) cannot participate.

Study focus: The first phase will explore different doses to determine the safest and most effective amount of treatment. The second phase will confirm the optimal dose and further assess how well the treatment works. Throughout the study, researchers will monitor how the treatment affects protein levels in the blood and collect information on safety and effectiveness. Participants will enter a long-term follow-up period after completing the main phases.

Investigational drug: BEAM-302 is a type of gene therapy designed to address the underlying genetic issues causing lung and liver problems. The study aims to find the best dose that provides the most benefit with the least side effects.

Study on the Safety and Tolerability of WVE-006 for Patients with Alpha-1 Antitrypsin Deficiency (AATD) Pi*ZZ

This study is testing WVE-006, an oligonucleotide medication (a small piece of genetic material designed to target specific genes), in participants with a specific genetic form of the deficiency known as Pi*ZZ.

Main inclusion criteria: Participants must be healthy or have mild to moderate lung disease with a lung function test result of at least 50%. They can also have stable mild liver disease with a FibroScan result of 10 kPa or less. They must have genetic testing confirming the Pi*ZZ type and have been a non-smoker for at least 1 year before screening. The study is open to both male and female participants.

Main exclusion criteria: People with any other serious health condition that could affect their safety or study results, pregnant or breastfeeding women, those who have had a recent infection or illness, people currently taking certain medications that might interfere, those with a history of allergic reactions to similar treatments, people who participated in another clinical trial recently, those with a history of substance abuse or alcohol dependency, people with mental health conditions that might affect participation, or those with a history of non-compliance with medical treatments are excluded.

Study focus: The study will monitor how the body processes the medication and any potential side effects through both single and multiple dose phases. Researchers will observe changes in M-AAT protein levels in the blood and measure medication concentrations over time. The study is expected to continue until the end of 2025.

Investigational drug: WVE-006 is administered through subcutaneous injection (under the skin). It is designed to interact with specific genetic components to increase the production of functional alpha-1 antitrypsin protein, addressing the underlying protein deficiency.

Study on the Safety of Self-Infusion Therapy with Human Alpha1-Proteinase Inhibitor for Patients with Severe Alpha-1 Antitrypsin Deficiency

This study is focused on assessing the safety of using Prolastin for self-infusion therapy at home over a 12-week period. The study aims to help patients manage their condition independently.

Main inclusion criteria: Participants must be at least 18 years old and able to understand and read German well enough to comprehend patient documents (a caregiver can help with writing if needed). They must have a documented diagnosis of severe deficiency and have been treated with Prolastin for at least 3 months with good tolerance. Participants must be able and willing to learn self-infusion at home, or have a caregiver who can do it. Someone must be available to monitor during each infusion. They must have access to and be able to use a device for phone and video calls with internet access to complete questionnaires. Participants must have suitable veins for venepuncture and a life expectancy of more than 3 years.

Main exclusion criteria: People with a known allergy or severe reaction to Prolastin, a history of severe allergic reactions (anaphylaxis) to any medication, those currently in another clinical trial or who participated in one within the last 30 days, people with a medical condition that doctors believe would make participation unsafe, pregnant or breastfeeding women, those with a history of drug or alcohol abuse within the past year, people with a serious illness or infection that is not well controlled, those who received a blood transfusion or blood products within the last 30 days, or people with a history of certain lung or liver diseases not related to the deficiency cannot participate.

Study focus: The study will train participants or their caregivers to perform the infusions at home and monitor the occurrence of adverse effects during the training and main study period. It will evaluate various health parameters, including lung function and patient satisfaction, to understand the impact of home-based self-infusion therapy.

Investigational drug: Prolastin is administered through intravenous infusion in dosages of 1000 mg, 4000 mg, or 5000 mg, depending on the specific product used. It provides the body with the alpha-1 antitrypsin protein that is lacking in these patients, helping to protect the lungs from damage.

Study Comparing INBRX-101 and Human Alpha1-Proteinase Inhibitor for Adults with Alpha-1 Antitrypsin Deficiency Emphysema

This study compares a new treatment called INBRX-101 to an existing therapy known as plasma-derived Alpha1-Proteinase Inhibitor augmentation therapy. The goal is to evaluate how well INBRX-101 works in maintaining certain protein levels in the blood over up to 32 weeks.

Main inclusion criteria: Participants must be between 18 and 80 years old with a confirmed diagnosis. They must show evidence of emphysema and have an FEV1 between 30% and 80% of the predicted value. They must be current non-smokers.

Main exclusion criteria: People with a known allergy or severe reaction to the study medication or its ingredients, those with a history of certain lung diseases other than emphysema caused by the deficiency, people who have had a recent lung infection or illness affecting breathing, those currently taking medications that could interfere with the study treatment, people with a history of drug or alcohol abuse, those with certain medical conditions that could affect study results or their safety, pregnant or breastfeeding women, and those unable to follow study procedures or attend scheduled visits are excluded.

Study focus: The study is designed as a double-blind trial, meaning neither participants nor researchers will know who is receiving which treatment. This helps ensure unbiased results. The study will include a placebo group receiving a solution without active treatment. Participants will have regular check-ups to monitor their health and the effects of the treatment. The study will assess safety, effectiveness, how the body processes the treatment, and whether any immune reactions develop.

Investigational drugs: INBRX-101 is administered as a concentrate for solution for infusion at a concentration of 50mg/ml. The alternative treatment, Respreeza, is given as a powder and solvent for solution for infusion. Both aim to maintain adequate levels of the protective protein in the blood to help prevent lung damage.

Summary

The 9 ongoing clinical trials for Alpha-1 Antitrypsin Deficiency represent a diverse range of therapeutic approaches, from inhaled medications to gene therapy. Several notable patterns emerge from this overview.

Geographically, most trials are concentrated in Western and Northern Europe, with Ireland, Sweden, and Germany appearing most frequently as trial locations. Several countries including Spain, Poland, Belgium, Austria, Netherlands, Portugal, and France are also hosting multiple studies. This concentration reflects both the expertise in rare disease research in these regions and potentially the prevalence of diagnosed cases.

Therapeutically, the trials can be grouped into several categories. Three trials are testing Fazirsiran (TAK-999), a gene-silencing medication aimed at treating liver complications. Two trials are evaluating INBRX-101, a protein replacement therapy for lung complications. Individual trials are testing Kamada-AAT (an inhaled therapy), BEAM-302 (a gene therapy), WVE-006 (an oligonucleotide therapy), and Prolastin (for home self-infusion). This diversity reflects the complexity of the condition, which affects both lungs and liver.

Most trials focus on adults between 18 and 80 years old, with specific genetic types of the deficiency (particularly PiZZ genotype). Several studies specifically target either lung manifestations (emphysema) or liver manifestations (fibrosis), while some address both. The variety of administration methods—from inhalation to subcutaneous injection to intravenous infusion—offers potential options for different patient preferences and clinical situations.

Many of these studies are in advanced phases of research, with some focusing on long-term safety and extension periods, suggesting that several treatments may be moving closer to potential regulatory approval.

Ongoing Clinical Trials on Alpha-1 antitrypsin deficiency

  • Study on the Safety of Self-Infusion Therapy with Human Alpha1-Proteinase Inhibitor for Patients with Severe Alpha-1 Antitrypsin Deficiency

    Recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany

  • Study on the Safety and Effectiveness of BEAM-302 with MR0005 and GR0015 for Adults with Alpha-1 Antitrypsin Deficiency-Related Lung or Liver Disease

    Recruiting

    1 1
    Investigated diseases:
    Investigated drugs:
    Ireland The Netherlands

  • A study comparing under-the-skin and into-the-vein alpha1-proteinase inhibitor treatment in patients with alpha1-antitrypsin deficiency

    Not yet recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Denmark Ireland The Netherlands Poland Portugal Spain +1

More information about
Alpha-1 antitrypsin deficiency:

Connected medications: