Chest
Volume 122, Issue 1, July 2002, Pages 66-74
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Clinical Investigations
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Biochemical Efficacy and Safety of a New Pooled Human Plasma α1-Antitrypsin, Respitin

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Background

Augmentation therapy with pooled human plasma-derived α1-antitrypsin (AAT) has been shown to have biochemical efficacy in restoring serum AAT levels above the protective threshold. Also, clinical efficacy has been suggested.

Objective

To evaluate the bioequivalence of a new solvent detergent-treated preparation of pooled human plasma-derived AAT (proposed name Respitin; Alpha Therapeutic Corporation; Los Angeles, CA) to the commercially available preparation (Prolastin; Bayer Corporation; West Haven, CT), we conducted a randomized controlled trial.

Methods

Eligible subjects were adults (> 18 years of age) who had never smoked or were ex-smokers, had severe deficiency of AAT, and had fixed airflow obstruction (ie, postbroncholdilator FEV1 of 30 to 80% of predicted values and/or diffusing capacity of the lung for carbon monoxide [Dlco] of < 70% of predicted values with evidence of emphysema on a CT scan). Of the 28 subjects recruited, 26 completed the 12-week comparison. Participants were randomized to receive Respitin (60 mg/kg once weekly; 14 subjects) or Prolastin (60 mg/kg once weekly; 14 subjects), and recipients of Prolastin then crossed over to receive Respitin thereafter for the 24-week duration of the study.

Results

The primary efficacy criteria were satisfied for equivalence to comparator (ie, the ratio of mean trough serum levels for Respitin/Prolastin at weeks 8 to 11 exceeded the efficacy criterion [0.905; p = 0.0206] as did the slope of the mean trough level over weeks 11 to 23 [−0.003 μmol per week]). In Respitin recipients, the trough serum antineutrophil elastase capacity at week 7 and at weeks 8 to 11 was also equivalent to the comparator, as was the rise in AAT levels in epithelial lining fluid from baseline to week 7. The levels of urinary elastin degradation products showed little appreciable change for > 24 weeks, and no difference between compared groups was shown through week 12. Adverse events were similarly infrequent in compared groups. Finally, neither spirometry measurements nor Dlco showed a significant change through 24 weeks.

Conclusions

We conclude that this new solvent detergent-treated pooled human plasma-derived AAT (Respitin) demonstrates biochemical equivalence to Prolastin and that this new drug is well-tolerated.

Section snippets

Study Drug

Respitin is a human α1-proteinase inhibitor. The product is derived from units of pooled human plasma, which have been tested and found to be nonreactive for hepatitis B surface antigen (HBsAg) and hepatitis C (HCV) antibody, and negative for antibodies to HIV-1 and HIV-2. All units of plasma that were used to prepare this drug had alanine aminotransferase levels that were less than twice the upper limit of normal of the expected range for the assay method used. To reduce the potential risk of

Results

A total of 28 subjects was recruited into the study (Table 2). Of the 14 subjects who were allocated to each drug, one patient withdrew from each group (due to unwillingness to adhere to the protocol in the study drug group and the development of pneumonia after the removal of an incidentally found airway foreign body during the baseline bronchoscopy in the control group), leaving 13 subjects in each study arm who completed the 12-week comparison. Baseline characteristics of the compared groups

Discussion

The main findings of this study are as follows: (1) a new solvent detergent-prepared, pooled, human plasma-derived α1-antiprotease called Respitin demonstrated equivalence to Prolastin in achieving trough serum AAT levels above the protective threshold of 11 μmol at weeks 8 to 11; (2) IV augmentation therapy with Respitin (60 mg/kg functionally active α1-antiprotease once weekly) maintained trough serum levels steadily (ie, with a slope exceeding −0.01 over weeks 11 to 23 of treatment); (3)

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This research was funded by the Alpha Therapeutic Corporation. Dr. Stoller's relationship to Alpha Therapeutic Corporation relates only to having served as the principal investigator in one of the study sites in the described trial. Neither any family member nor he has any ongoing financial or consultative interests in this company or product. He also serves as an investigator or consultant to studies sponsored by other companies developing α1-antitrypsin deficiency-relevant products, including Bayer, Aventis Behring, and Baxter. Dr. Brantly had a clinical study contract with Alpha Therapeutic Corporation to perform the testing of samples while he was an employee of the National Heart, Lung, and Blood Institute at the National Institutes of Health and of the University of Florida. He does not own stock in Alpha Therapeutic Corporation, nor has he been a paid consultant on the speakers bureau of Alpha Therapeutic Corporation. Dr. Dweik received nothing of value from any commercial party related directly or indirectly to the subject of this article. Dr. Clausen has no financial interests in Alpha Therapeutic Corporation nor in the product that has evolved, other than serving as principal investigator for the University of California San Diego site in this study. Alpha Therapeutic Corporation paid a reasonable and customary fee for Dr. Campbell's portion of the work involved in the completion of this study. He has no other financial connection with Alpha Therapeutic Corporation. Bayer Corporation currently markets a product that is similar to, and will compete with, Respitin. Dr. Campbell has been a consultant for Bayer Corporation, and Bayer Corporation has provided financial support for a clinical diagnostic laboratory (HerediLab, Inc) for which he serves as Laboratory Director. Otherwise, he has no equity interest in any organization that has a direct financial interest in the broad subject area discussed in the manuscript. Dr. Stock's only tie to the product Respitin and to Alpha Therapeutic Corporation was as an investigator in the clinical research trial described in this article through his appointment at the University of Texas Health Center. Neither his family members nor he has any ongoing financial or consultative interests in this company or the product in question. Dr. Stock has active research contracts with companies (Aventis Behring and the American Red Cross) that have potential competitors to Respitin in clinical trial. Mr. Rouhani worked with Dr. Brantly at the National Heart, Lung, and Blood Institute at the National Institutes of Health to perform the testing of samples from Alpha Therapeutic Corporation. Furthermore, he neither owns any stock nor has any financial interest in Alpha Therapeutic Corporation. At the time that the work described in the article was performed, Dr. Norton was an employee of the Alpha Therapeutic Corporation. Other than compensation for that position, he received no compensation from any other source for Respitin or any other drug for the treatment of α1-antitrypsin deficiency. At the time that the work described in this article was performed, Ms. Shahin was an employee of Alpha Therapeutic Corporation. Other than compensation for that position, she received no compensation from any other source for work performed on Respitin or any other drug for the treatment of α1-antitrypsin deficiency.

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