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

NCT02870309 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: GTI1401JapicCTI-163160
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

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.

Conditions

Alpha1-Antitrypsin Deficiency

Outcome Measures

Primary Outcomes (5)

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

  An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether considered related to the medicinal product. TEAEs were defined as any AE occurring after or on the first Alpha-1 MP infusion until the final visit of study.

  Up to Week 12

• Number of Participants With Adverse Drug Reaction (ADRs)

  ADRs were defined as adverse events (AEs) which were in the investigator's opinion of causal relationship to the study treatment. AE was defined as any unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product.

  Up to Week 12

• Number of Participants With Serious Adverse Events (SAEs)

  A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  Up to Week 12

• Number of Discontinuations Due to Adverse Events (AEs) or Serious Adverse Events (SAEs)

  An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether considered related to the medicinal product. TEAEs were defined as any AE occurring after or on the first Alpha-1 MP infusion until the final visit of study. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

  Up to Week 12

• Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

  COPD exacerbation was defined as an increase in respiratory symptoms (dyspnea, increased cough, and/or production of sputum) over baseline that usually requires medical intervention.

  Up to Week 12

Secondary Outcomes (1)

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

  Baseline (Week 1), Weeks 7, 8 (prior to the start of infusions of Alpha-1 MP) and Week 9 (168 hours post infusion)

Study Arms (1)

Alpha-1 MP

EXPERIMENTAL

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.

Biological: Alpha-1 MP

Interventions

Alpha-1 MP BIOLOGICAL

Alpha-1 MP is a stable, sterile, lyophilized preparation of human alpha1-PI, also known as α1-antitrypsin

Also known as: Prolastin-C

Alpha-1 MP

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grifols Therapeutics LLC: lead
• Grifols Japan K.K.: collaborator

Study Sites (2)

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

Related Publications (1)

• Seyama K, Nukiwa T, Sato T, Suzuki M, Konno S, Takahashi K, Nishimura M, Steinmann K, Sorrells S, Chen J, Hayashi KI. Safety and pharmacokinetics of Alpha-1 MP (Prolastin(R)-C) in Japanese patients with alpha1-antitrypsin (AAT) deficiency. Respir Investig. 2019 Jan;57(1):89-96. doi: 10.1016/j.resinv.2018.09.006. Epub 2018 Nov 8.

  PMID: 30416054 DERIVED

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Interventions

Mp alpha1 receptor

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Susan Sorrells
• Organization: Grifols Therapeutics LLC

susan.sorrells@grifols.com

919-316-6582

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2016
• First Posted: August 17, 2016
• Study Start: July 29, 2016
• Primary Completion: March 15, 2017
• Study Completion: March 15, 2017
• Last Updated: October 28, 2021
• Results First Posted: February 18, 2021

Record last verified: 2021-10

Locations

JP (2)