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
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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
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Verification Date
October 2021