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

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Brief Title

Safety and Pharmacokinetics of Alpha-1 MP in Patients 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 for 8 weeks.
    

Detailed Description

      This study is a multicenter, open-label trial to evaluate the safety and pharmacokinetics of
      weekly intravenous infusions of 60 mg/kg of the investigational drug in subjects with AATD.
      The trial will be conducted at approximately 5 medical institutions in Japan, aiming to
      enroll a minimum of 3 adult subjects 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 PK evaluation period for 1 week. At the Week 9 visit when the PK evaluation period is
      completed, subjects will be asked whether they would like to participate in an extension
      trial (GTI1401-OLE). For subjects 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. Subjects 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), subjects will be evaluated for eligibility for participation during the screening
      period. Subjects considered eligible will enter the 8-week treatment period to receive a
      total of 8 weekly intravenous infusions of 60 mg/kg of Alpha-1 MP. The initial intravenous
      infusion will be given at the Week 1 (baseline) visit. During the treatment period, subjects
      will receive weekly intravenous infusions of Alpha-1 MP at the Weeks 1 (baseline), 2, 3, 4,
      5, 6, 7, and 8 visits. After the last intravenous infusion of Alpha-1 MP at the Week 8 visit,
      subjects will enter the 1-week PK evaluation period. During this PK evaluation period,
      subjects 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), subjects will visit the study center for follow-up/study completion (Week 12).
      All subjects 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, subjects will be asked whether they would like to participate in the
      extension trial (GTI1401-OLE). Subjects intending to participate in the extension trial will
      be able to continue the treatment with intravenous infusions of 60 mg/kg of Alpha-1 MP for at
      least another year (subjects 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. Subjects 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

Safety of 60 mg/kg Alpha-1 MP assessed by Adverse events, ADRs, serious AEs (SAEs), discontinuations due to AEs or SAEs, and COPD exacerbations

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:  IV infusions of 60 mg/kg Alpha-1 MP administered weekly over 8 weeks at an infusion rate not to exceed 0.08 mL/kg/min over approximately 15 minutes

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

January 2016

Completion Date

March 2017

Primary Completion Date

March 2017

Eligibility Criteria

        Inclusion Criteria:

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

          -  Subjects with clinically apparent pulmonary emphysema diagnosed by CT scan

          -  AATD subjects with documented serum alpha1-PI levels of <50 mg/dL (i.e., 11 µM) as
             measured by nephelometry. In subjects 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.

          -  Subjects whose percentage of forced expired 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 COPD]

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

        Exclusion Criteria:

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

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

          -  Subjects who have undergone lung transplantation or liver transplantation

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

          -  Subjects with increased liver enzymes (AST, ALT, and ALP) ≥2.5 times the upper limit
             of normal

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

          -  Subjects 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 subjects who have a partner who is of childbearing
             potential and is unwilling to use effective contraceptive methods throughout the trial
             period.

          -  Subjects with a past history of HAV, HBV, HCV, or HIV infection, or subjects currently
             presenting with clinical signs or symptoms suggestive of such infection

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

          -  Subjects participating in another clinical trial within 4 weeks before the Week

             1 (baseline) visit

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

          -  Subjects 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)

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

          -  Subjects with a previous or current diagnosis of selective, severe IgA deficiency

          -  Subjects who are mentally challenged and cannot independently give consent

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

          -  Subjects who have medical conditions that may confound the results of this clinical
             trial or may endanger other subjects 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


Responsible Party

Sponsor

Study Sponsor

Grifols Therapeutics LLC

Collaborators

 Grifols Japan K.K.

Study Sponsor

, , 


Verification Date

June 2017