Phase 3
N=34
GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study
Alpha1-antitrypsin Deficiency
Bottom Line
View on ClinicalTrials.gov: NCT02525861 ↗Enrolled (actual)
34
Serious AEs
5.9%
Results posted
Oct 2021
Primary outcome: Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Potentially Related to Presence of Particle Load in the GLASSIA Solution — 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- GLASSIA (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Baxalta now part of Shire
- Primary completion
- Jul 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Potentially Related to Presence of Particle Load in the GLASSIA Solution |
0; 0 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Reactions (ARs) Plus Suspected Adverse Reactions (ARs) Within 24 Hours Following the End of IP Infusion |
7; 3 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Reactions (ARs) Plus Suspected Adverse Reactions (ARs) Within 72 Hours Following the End of IP Infusion |
10; 7 | — |
| PRIMARY Number of Infusions Discontinued, Slowed, or Interrupted Due to TEAEs |
0; 0; 1; 0; 0; 0 | — |
| PRIMARY Number of Participants Who Developed Binding and/or Neutralizing Anti- Alpha1-Proteinase Inhibitor(A1PI) Antibodies |
1; 1; 1; 1 | — |
| PRIMARY Change From Baseline in Antigenic Alpha1-Proteinase Inhibitor (A1PI) Levels in Epithelial Lining Fluid (ELF) |
0.515 | <0.001 sig |
| PRIMARY Change From Baseline in Functional Alpha1-Proteinase Inhibitor(A1PI) Levels in Epithelial Lining Fluid (ELF) |
0.256 | <0.001 sig |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
13; 9 | — |
| SECONDARY Number of Participants Who Experienced a Shift From Normal or Clinically Non-significant Abnormal Laboratory Values at Baseline to Clinically Significant Abnormal Laboratory Values at Week 13, 25, and 26 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Treatment-Emergent Seroconversion or Positive Nucleic Acid Test (NAT) for Parvovirus B19 (B19V) |
0; 1; 0; 0; 0; 0 | — |
Summary
The purpose of the study is 2-fold: (1) to evaluate the safety and potential immunogenicity of GLASSIA following intravenous (IV) administration via in-line filtration; and (2) to assess the effects of GLASSIA augmentation therapy on the levels of A1PI and various biomarkers in the epithelial lining fluid (ELF) following intravenous (IV) administration at a dosage of 60 milligrams per kilogram (mg/kg) Body weight (BW)/week active alpha1-proteinase inhibitor (A1PI) protein for 25 weeks in participants with emphysema due to congenital A1PI deficiency.
Eligibility Criteria
Inclusion Criteria
- Male or female participants meeting the following age criteria:
- For participants who will undergo bronchoscopy/ bronchoalveolar lavage (BAL) procedures: 18 to 75 years of age at the time of screening.
- For participants who will be waived from undergoing bronchoscopy/BAL procedures: 18 years of age or older at the time of screening.
- Documented Alpha1-Proteinase Inhibitor (A1PI) genotype of Pi*Z/Z, Pi*Z/Null, Pi*Malton/Z, Pi*Null/Null, or other "at-risk" allelic combinations such as SZ (excluding MS and MZ without the presence of another allowable at-risk genotype) and an endogenous A1PI plasma levels of less than or equal to ( or =) 50 percentage (%) of predicted.
- If FEV1 is >80% predicted, then FEV1/forced vital capacity (FVC) must be or =40 millimeters) of mercury [mm Hg]).
- The participant routinely produces more than 1 tablespoon of sputum per day.
- The participant has a history of frequent pulmonary exacerbations (greater than 2 moderate or severe exacerbations within 52 weeks prior to screening.
- The participant is experiencing a pulmonary exacerbation at the time of screening (participant may be rescreened 4 weeks after the clinical resolution of an exacerbation).
- The participant has clinically significant abnormalities (other than emphysema, chronic bronchitis, or mild bronchiectasis) detected on chest X-ray or CT scan at the time of screening (past records obtained within 52 weeks prior to screening may be used, if available).
- The participant has clinically significant abnormalities detected on a 12-lead electrocardiogram (ECG) performed at the time of screening (past records obtained within 26 weeks prior to screening may be used, if available).
- The participant has clinically significant congestive heart failure with New York Heart Association (NYHA) Class III/IV symptoms.
- The participant is experiencing an active malignancy or has a history of malignancy within 5 years prior to screening, with the exception of the following: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or stable prostate cancer not requiring treatment.
- The participant has a history of lung or other organ transplant, is currently on a transplant list, or has undergone major lung surgery.
- The participant is receiving long-term around-the-clock oxygen (O2) supplementation. (The following are allowed: short-term use of oxygen supplementation [eg, for the management of acute COPD exacerbation], O2 supplementation required during night time only, and supplemental O2 with continuous positive airway pressure [CPAP] or bi-level positive airway pressure [BiPAP]).
- Known history of hypersensitivity following infusions of human blood or blood components.
- Immunoglobulin A (IgA) deficiency ( 3.0 times upper limit of normal (ULN)
- Serum total bilirubin >2.0 times ULN
- >2+proteinuria on urine dipstick analysis
- Serum creatinine >2.0 times ULN
- Absolute neutrophil count (ANC) 4 weeks) immunosuppressive therapy, such as systemic corticosteroids at doses greater than 10 mg/day of prednisone (or its equivalent), mycophenolate mofetil, azathioprine, cyclophosphamide, and rituximab.
- If a participant is receiving anticoagulant or anti-platelet therapy (such as warfarin and clopidogrel), the participant is unwilling to or unable to safely discontinue anticoagulant or anti-platelet therapy within 7 days prior to until at least 24 hours after the BAL procedures. An exception is low-dose aspirin alone which is allowed.
Data sourced from ClinicalTrials.gov (NCT02525861). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.