Safety and Pharmacokinetics of Alpha-1 MP in Patients With Alpha1-Antitrypsin Deficiency

Related Clinical Trial
Functional and Structural Lung Imaging in Chronic Obstructive Pulmonary Disease A Study of Belcesiran in Patients With A1ATD-Associated Liver Disease A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Participants With Alpha1-Antitrypsin Deficiency Evaluation of the Efficacy and Safety of VX-864 in Subjects With the PiZZ Genotype A Single Ascending and Repeated Dose Study of Oral ZF874 in Healthy Volunteers and PiMZ Subjects ARALAST NP Alpha-1 Lung Density Chronic Obstructive Pulmonary Disease-Emphysema (COPD-E) Study Early Access Program Using Alpha 1 Antitrypsin Infusion for Patients With Steroid Refractory Acute GvHD After Hematopoietic Stem Cell Transplantation (HSCT) Characterization of the Pathobiology of Early Lung Destruction in Alpha 1-Antitrypsin Deficient Individuals COPD Exacerbation Blood and Urine Biomarkers Study Alpha-1 Carrier Genomics Study Evaluation of the Efficacy and Safety of VX-814 in Subjects With the PiZZ Genotype Study of ARO-AAT in Normal Adult Volunteers Safety Study of Alfalastin (Human Alpha-1 Antitrypsin) Administered at Home AL1TER™: Alpha-1 Therapy, Evaluation, and Research Patient Registry Respreeza® Self-administration and Learning Program (AmAREtTI Study) Experimental Gene Transfer Procedure to Treat Alpha 1-Antitrypsin (AAT) Deficiency Lung Disease and Its Affect on the Work of White Blood Cells in the Lungs A 12-week Study Treating Participants Who Have alpha1-antitrypsin-related COPD With Alvelestat (MPH966) or Placebo. Environment Effect on Six-Minute Walk Test Performance Alpha-1 Foundation DNA and Tissue Bank Alpha1-antitrypsin Deficiency Registry Alpha-1 Research Registry Stage 1 Study of ARALAST NP and GLASSIA in A1PI Deficiency Alpha-1 Coded Testing(ACT) Study Long-Term Follow-up Study of ADVM-043 Safety Dose Finding Study of ADVM-043 Gene Therapy to Treat Alpha-1 Antitrypsin (A1AT) Deficiency 4-PBA: Will it Increase the Level of Alpha 1-Antitrypsin(AAT) in Persons With AAT Deficiency? Experimental Gene Transfer Procedure to Treat Alpha 1-Antitrypsin Deficiency Management of Patients With Alpha-1 Antitrypsin Deficiency Associated Emphysema Phase II, Safety and Efficacy Study of Kamada-alpha-1-antitrypsin (AAT) for Inhalation” EARCO REGISTRY. History Of Patients With Alpha-1 Antitrypsin GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study Safety, Tolerability and Effect of ARC-AAT Injection on Circulating and Intrahepatic Alpha-1 Antitrypsin Levels Efficacy/Safety of HA Inhalation Solution for Hereditary Emphysema in Patients With Alpha-1 Antitrypsin Deficiency Safety and Pharmacokinetics of Alpha-1 MP in Patients With Alpha1-Antitrypsin Deficiency Phase II/III Study of an Alpha-1 Proteinase Inhibitor (Kamada-API) in Individuals With Alpha-1 Antitrypsin Deficiency Study of the Effect of Aerosolized, Recombinant Alpha 1-Antitrypsin on Epithelial Lining Fluid Analytes in Subjects With Alpha 1-Antitrypsin Deficiency Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency The Safety and Tolerability of Alpha-1 Modified Process (MP) In Subjects With Alpha-1-antitrypsin (AAT) Deficiency Lung Volume Reduction Coils for Emphysema in Alpha-1 Antitrypsin Deficiency Study of Genotype and Phenotype in Patients With Alpha 1-Antitrypsin Deficiency Alpha-1 Foundation Research Registry Targeting Pulmonary Perfusion in Alpha-1 Antitrypsin Deficiency Effects of Exercise Training in Chronic Obstructive Pulmonary Disease Versus Alpha-1-Antitrypsin-deficiency-patients Evaluate Efficacy and Safety of “Kamada-AAT for Inhalation” in Patients With AATD A Study of DCR-A1AT in Healthy Adult Volunteers and Patients With A1ATD-Associated Liver Disease Safety & Efficacy Study of rAAV1-CB-hAAT for Alpha-1 Antitrypsin Deficiency Effects of Different Exercise Training Modalities in Alpha-1 Antitrypsin Deficiency Patients Safety Study of an Aerosolized, Recombinant Alpha 1-Antitrypsin in Subjects With Alpha 1-Antitrypsin Deficiency Study Comparing Weekly Intravenous Administration of OctaAlpha1 With a Marketed Preparation Glassia® in Subjects With Alpha-1-antitrypsin Deficiency Long-term Safety of Alpha1-Proteinase Inhibitor (Human) in Japanese Subjects With Alpha1 Antitrypsin Deficiency (GTI1401-OLE) Efficacy and Safety Study of Augmentation Therapy With ARALAST Fraction IV-1 (Human Alpha 1 – Proteinase Inhibitor) Aralast alpha1-proteinase Inhibitor Surveillance Study Pharmacokinetic Study of ARALAST (Human Alpha1- PI) The Use of High Resolution Chest Computed Tomography in Alpha-1 Antitrypsin Deficiency Prevalence of Alpha-1 Antitrypsin Deficiency in Chronic Obstructive Pulmonary Disease (COPD) Comparison of Pharmacokinetic, Safety, Tolerability of Alpha-1 MP and Prolastin In Alpha1-antitrypsin Deficient Adults Phase 1 Study to Assess the Safety, PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency The Impact of Delayed Diagnosis of Alpha-1 Antitrypsin Deficiency Epigenetic Regulation of Immunity in Alpha-1 Anti-trypsin Deficiency Microbioma in Sputa From COPD With Alpha-1 Antitrypsin Deficiency A Study of ARC-AAT in Healthy Volunteer Subjects and Patients With Alpha-1 Antitrypsin Deficiency (AATD) A Study to Assess Safety and PK of Liquid Alpha₁-Proteinase Inhibitor (Human) in Treating Alpha₁-Antitrypsin Deficiency

Brief Title

Safety and Pharmacokinetics of Alpha-1 MP (Alpha1-proteinase Inhibitor (Human), Modified Process) in Participants With Alpha1-Antitrypsin Deficiency

Official Title

Phase I/II Multicenter, Open-label Trial to Evaluate the Safety and Pharmacokinetics of Alpha-1 MP in Patients With Alpha1-Antitrypsin Deficiency

Brief Summary

      This study is a multicenter, open-label trial to evaluate the safety and pharmacokinetics of
      weekly intravenous infusions of 60 mg/kg of Alpha-1 MP (alpha1-proteinase inhibitor (human),
      modified process) for 8 weeks.
    

Detailed Description

      This study is a multicenter, open-label trial to evaluate the safety and pharmacokinetics of
      weekly intravenous (IV) infusions of 60 mg/kg of the investigational drug in participants
      with alpha1-antitrypsin deficiency (AATD). The trial will be conducted at approximately 5
      medical institutions in Japan, aiming to enroll a minimum of 3 adult participants or more.
      The trial will consist of a screening period scheduled within 3 weeks before trial entry, an
      open-label treatment period for 8 weeks, and a pharmacokinetic (PK) evaluation period for 1
      week. At the Week 9 visit when the PK evaluation period is completed, participant will be
      asked whether they would like to participate in an extension trial (GTI1401-OLE). For
      participants not intending to participate in the extension trial, the date of follow-up/study
      completion visit (30 days [4 weeks] after the last dose of the investigational drug) will be
      arranged. Participants will participate in this trial for approximately 14 weeks from the
      start of the screening period through the completion of the trial.

      At the screening visit (scheduled within 3 weeks before trial entry), after providing
      informed consent (agreement based on adequate explanation and understanding of the treatment
      plan), participants will be evaluated for eligibility for participation during the screening
      period. Participants considered eligible will enter the 8-week treatment period to receive a
      total of 8 weekly IV infusions of 60 mg/kg of Alpha-1 MP. The initial IV infusion will be
      given at the Week 1 (baseline) visit. During the treatment period, participants will receive
      weekly IV infusions of Alpha-1 MP at the Weeks 1 (baseline), 2, 3, 4, 5, 6, 7, and 8 visits.
      After the last IV infusion of Alpha-1 MP at the Week 8 visit, participants will enter the
      1-week PK evaluation period. During this PK evaluation period, participants will visit the
      study center to undergo blood sampling for PK evaluation at the PK1 visit (the next day of
      the Week 8 visit), the PK2 visit (2 days after the Week 8 visit), the PK5 visit (5 days after
      the Week 8 visit), and at the Week 9 visit. At 30 days after the last dose (Week 8),
      participants will visit the study center for follow-up/study completion (Week 12). All
      participants will undergo blood sampling for the measurement of alpha1-PI trough
      concentrations at the Weeks 1 (baseline), 7, and 8 visits (blood samples will be collected
      before dosing) as well as at the Week 9 visit.

      Blood samples for the evaluation of PK parameters will be collected from Week 8 to Week 9.
      The blood sample collected before the infusion of Alpha-1 MP at the Week 8 visit and the
      blood sample for PK evaluation collected at the Week 9 visit (7 days after the infusion at
      the Week 8 visit) will be also used for the measurement of alpha1-PI trough concentrations
      for Weeks 8 and 9.

      At the Week 9 visit, participants will be asked whether they would like to participate in the
      extension trial (GTI1401-OLE). Participants intending to participate in the extension trial
      will be able to continue the treatment with IV infusions of 60 mg/kg of Alpha-1 MP for at
      least another year (participants will be further asked whether they would like to continue
      the treatment at yearly intervals) for the purpose of evaluation of the safety of long-term
      Alpha-1 MP treatment. Participants not intending to enter the extension trial will visit the
      study center for follow-up/study completion at 30 days (4 weeks) after the last dose of
      Alpha-1 MP (Week 12).
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Secondary Outcome

 Trough Level of Total alpha1-PI for Weekly IV Infusions of 60 mg/kg Alpha-1 MP

Condition

Alpha1-Antitrypsin Deficiency

Intervention

Alpha-1 MP

Study Arms / Comparison Groups

 Alpha-1 MP
Description:  Participants received 8 IV infusions of 60 mg/kg Alpha-1 MP administered weekly at an infusion rate not exceeding 0.08 mL/kg/min over approximately 15 minutes, up to Week 8.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

4

Start Date

July 29, 2016

Completion Date

March 15, 2017

Primary Completion Date

March 15, 2017

Eligibility Criteria

        Inclusion Criteria:

          -  Participants aged ≥20 years at the time of providing informed consent.

          -  Participants with clinically apparent pulmonary emphysema diagnosed by Computed
             Tomography (CT) scan.

          -  AATD participants with documented serum alpha1-PI levels of <50 mg/dL (i.e., 11 µM) as
             measured by nephelometry. In participants with no previously documented serum
             alpha1-PI levels, their serum alpha1-PI levels measured by nephelometry during the
             screening period must be <50 mg/dL.

          -  Participants whose percentage of forced expired volume in 1 second/forced vital
             capacity forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) after
             inhalation of a bronchodilator is <70% during the screening period [equivalent to the
             criterion for the diagnosis of chronic obstructive pulmonary disease (COPD)].

          -  Participants who are willing to and able to provide signed written informed consent.

        Exclusion Criteria:

          -  Participants with moderately or severely deteriorated lung function in the 4 weeks
             before the Week 1 (baseline) visit.

          -  Participants whose percentage of forced expired volume in 1 second/forced vital
             capacity (%FEV1 after inhalation of a bronchodilator is <30% during the screening
             period.

          -  Participants who have undergone lung transplantation or liver transplantation.

          -  Participants who have undergone any lung surgery (excluding lung biopsy) in the past 2
             years.

          -  Participants with increased liver enzymes aspartate aminotransferase, alanine
             aminotransferase and alkaline phosphatase (AST, ALT, and ALP) ≥2.5 times the upper
             limit of normal.

          -  Participants with severe complications including but not limited to congestive heart
             failure and liver cirrhosis.

          -  Participants who have developed any malignant tumor (including malignant melanoma;
             however, other forms of skin cancer are excluded) in the past 5 years.

          -  Pregnant women, breastfeeding women, or women of childbearing potential who do not
             intend to use effective contraceptive methods (use of oral, injection, or implant
             hormonal contraceptives; placement of an intrauterine device (IUD) or intrauterine
             contraceptive system; concomitant use of spermatocidal foam, gel, film, cream,
             suppository and condoms or cervical caps; male sterilization; or abstinence)
             throughout the trial period or male participants who have a partner who is of
             childbearing potential and is unwilling to use effective contraceptive methods
             throughout the trial period.

          -  Participants with a past history of hepatitis A virus, hepatitis B virus, hepatitis C
             virus, or human immunodeficiency virus (HAV, HBV, HCV, or HIV) infection, or
             participants currently presenting with clinical signs or symptoms suggestive of such
             infection.

          -  Participants with a smoking history in the past 6 months, or participants tested
             positive for urinary cotinine levels at the screening visit.

          -  Participants participating in another clinical trial within 4 weeks before the Week 1
             (baseline) visit.

          -  Participants with a history of anaphylactic or severe systemic reactions to any plasma
             derived alpha1-PI product or other blood products.

          -  Participants who have continuously received any systemic steroid therapy at a
             prednisone-equivalent dose >5 mg/day within 4 weeks before the Week 1 (baseline) visit
             (Note: inhaled steroids are not regarded as systemic steroids).

          -  Participants who have used any systemic or aerosolized antibiotic drug for the
             treatment of COPD exacerbation within 4 weeks before the Week 1(baseline) visit.

          -  Participants with a previous or current diagnosis of selective, severe Immunoglobulin
             A (IgA) deficiency.

          -  Participants who are mentally challenged and cannot independently give consent.

          -  Participants who have difficulty in adhering to the protocol or its procedures in the
             opinion of the investigator.

          -  Participants who have medical conditions that may confound the results of this
             clinical trial or may endanger other participants during the participation in this
             clinical trial in the opinion of the investigator.
      

Gender

All

Ages

20 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

Japan

Location Countries

Japan

Administrative Informations


NCT ID

NCT02870309

Organization ID

GTI1401

Secondary IDs

JapicCTI-163160

Responsible Party

Sponsor

Study Sponsor

Grifols Therapeutics LLC

Collaborators

 Grifols Japan K.K.

Study Sponsor

, , 


Verification Date

January 2021