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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-001189-14 | EudraCT Number |
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The purpose of this study is to examine the safety, tolerability, immunogenicity and the way the body absorbs, distributes, breaks down and excretes various increasing single and multiple subcutaneous doses of PA401 in healthy subjects.
This study will also look at the effect of PA401 on inflammation in the lungs following an inhaled lipopolysaccharide (LPS) challenge (LPS is a bacterial cell wall fragment) and sputum induction (a procedure performed to help to cough up sputum (phlegm)) after a single subcutaneous dose of two dose levels.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PA401 | Experimental | PA401 is a potent inhibitor of neutrophil activation and transmigration under development as a novel parenteral anti-inflammatory therapy for respiratory indications such as chronic obstructive pulmonary disease (COPD) and Cystic Fibrosis (CF). PA401 is a genetically engineered and recombinantly expressed mutant of the bioactive form of human interleukin-8. |
|
| Placebo | Placebo Comparator | Placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PA401 | Biological | Part A of Study: Subcutaneous, 0.1mg to 50mg, single ascending doses Part B of Study: Subcutaneous, up to 17.1mg, single dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Treatment Emergent Adverse Events | up to 14 days post dose | |
| Immunogenicity | Anti-drug antibody data | Up to 28 days post dose |
| Assessment of the Effect of PA401 on Induced Sputum Total Neutrophils | Induced sputum was collected 6 hours after lipopolysaccharide challenge (5.5 hours following dosing) and assessed for neutrophils | 5.5 hours post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) | Up to 12 time-points up to 48 hours post dose | |
| Pharmacokinetic Parameters: Time of Occurrence of the Maximum Observed Plasma Concentration (Tmax) | Up to 12 time-points up to 48 hours post dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jim Ritter, MD | Quintiles, Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Quintiles | London | SE1 1YR | United Kingdom |
In Part B, subjects were included at baseline if they had a baseline neutrophil level in induced sputum of ≤70%
The study was conducted from June 2012 (first subject dosed) to April 2013 (last subject visit). The study was conducted in 2 parts; Part A was a single ascending dose study, Part B was a randomised placebo-controlled study to investigate the effect of a single dose of PA401 on sputum neutrophils following inhaled lipopolysaccharide challenge
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A PA401 0.1 mg | |
| FG001 | Part A PA401 0.3 mg | |
| FG002 | Part A PA401 1.0 mg | |
| FG003 | Part A PA401 3.0 mg | |
| FG004 | Part A PA401 10 mg | |
| FG005 | Part A Placebo | |
| FG006 | Part B PA401 1.0 mg | PA401 1.0 mg was administered 30 minutes after lipopolysaccharide challenge |
| FG007 | Part B PA401 3.0 mg | PA401 3.0 mg was administered 30 minutes after lipopolysaccharide challenge |
| FG008 | Part B Placebo | Placebo was administered 30 minutes after lipopolysaccharide challenge |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A | |
| BG001 | Part B | |
| BG002 | Total |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Treatment Emergent Adverse Events | Safety analyses were performed on all subjects who receive a dose of PA401 or placebo and who had any post-dose measurements | Posted | Number | Participants | up to 14 days post dose |
|
Up to 14 days post dose
Adverse events were monitored by the clinical staff asking non-leading questions during the period of confinement to the clinic.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A PA401 0.1 mg |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial Fibrillation | Cardiac disorders | MedDRA (15.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tinnitus | Ear and labyrinth disorders | MedDRA (15.0) | Systematic Assessment |
Part B of the study was terminated early which led to a small number of subjects analyzed. Pharmacokinetic parameters were not calculated for Part A 0.3mg and 10 mg PA401
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| ProtAffin Biotechnologie AG | ProtAffin Biotechnologie AG | office@protaffin.com |
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| Placebo | Other | Subcutaneous |
|
| Pharmacokinetic Parameters: Terminal Half-life (t1/2) | Up to 12 time-points up to 48 hours post dose |
| Pharmacokinetic Parameters: Area Under the Plasma Concentration-time Curve From Zero to Infinity | Up to 12 time-points up to 48 hours post dose |
| Assessment of the Effect of PA401 on Induced Sputum Percentage Neutrophils | Induced sputum was collected 6 hours after lipopolysaccharide challenge (5.5 hours following dosing) and assessed for neutrophils | 5.5 hours post dose |
Total of all reporting groups
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| OG004 |
| Part A PA401 10 mg |
| OG005 | Part A Placebo |
| OG006 | Part B PA401 1.0 mg |
| OG007 | Part B PA401 3.0 mg |
| OG008 | Part B Placebo |
|
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| Primary | Immunogenicity | Anti-drug antibody data | Safety analyses were performed on all subjects who received a dose of PA401 or placebo and who had any post-dose assessments | Posted | Number | participants | Up to 28 days post dose |
|
|
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| Secondary | Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) | Posted | Mean | Standard Deviation | ng/mL | Up to 12 time-points up to 48 hours post dose |
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|
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| Secondary | Pharmacokinetic Parameters: Time of Occurrence of the Maximum Observed Plasma Concentration (Tmax) | Posted | Mean | Standard Deviation | hours | Up to 12 time-points up to 48 hours post dose |
|
|
|
| Secondary | Pharmacokinetic Parameters: Terminal Half-life (t1/2) | Posted | Mean | Standard Deviation | hours | Up to 12 time-points up to 48 hours post dose |
|
|
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| Secondary | Pharmacokinetic Parameters: Area Under the Plasma Concentration-time Curve From Zero to Infinity | Posted | Mean | Standard Deviation | ng.h/mL | Up to 12 time-points up to 48 hours post dose |
|
|
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| Primary | Assessment of the Effect of PA401 on Induced Sputum Total Neutrophils | Induced sputum was collected 6 hours after lipopolysaccharide challenge (5.5 hours following dosing) and assessed for neutrophils | Posted | Least Squares Mean | 95% Confidence Interval | x10e6 cells/g | 5.5 hours post dose |
|
|
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| Secondary | Assessment of the Effect of PA401 on Induced Sputum Percentage Neutrophils | Induced sputum was collected 6 hours after lipopolysaccharide challenge (5.5 hours following dosing) and assessed for neutrophils | Posted | Least Squares Mean | 95% Confidence Interval | percentage of total cells | 5.5 hours post dose |
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|
|
| 0 |
| 4 |
| 3 |
| 4 |
| EG001 | Part A PA401 0.3 mg | 0 | 4 | 3 | 4 |
| EG002 | Part A PA401 1.0 mg | 0 | 4 | 4 | 4 |
| EG003 | Part A PA401 3.0 mg | 0 | 4 | 2 | 4 |
| EG004 | Part A PA401 10 mg | 1 | 2 | 2 | 2 |
| EG005 | Part A Placebo | 0 | 9 | 3 | 9 |
| EG006 | Part B PA401 1.0 mg | 0 | 10 | 7 | 10 |
| EG007 | Part B PA401 3.0 mg | 0 | 5 | 5 | 5 |
| EG008 | Part B Placebo | 0 | 7 | 4 | 7 |
| Vision Blurred | Eye disorders | MedDRA (15.0) | Systematic Assessment |
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| Photophobia | Eye disorders | MedDRA (15.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Gastrointestinal Disorder | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Mouth Ulceration | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Abdominal Discomfort | Gastrointestinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (15.0) | Systematic Assessment |
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| Injection Site Pruritus | General disorders | MedDRA (15.0) | Systematic Assessment |
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| Injection Site Erythema | General disorders | MedDRA (15.0) | Systematic Assessment |
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| Influenza Like Illness | General disorders | MedDRA (15.0) | Systematic Assessment |
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| Chills | General disorders | MedDRA (15.0) | Systematic Assessment |
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| Chest Discomfort | General disorders | MedDRA (15.0) | Systematic Assessment |
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| Oedema Peripheral | General disorders | MedDRA (15.0) | Systematic Assessment |
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| Injection Site Reaction | General disorders | MedDRA (15.0) | Systematic Assessment |
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| Viral Infection | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA (15.0) | Systematic Assessment |
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| Excoriation | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA (15.0) | Systematic Assessment |
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| C-Reactive Protein Increased | Investigations | MedDRA (15.0) | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (15.0) | Systematic Assessment |
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| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
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| Musculoskeletal Stiffness | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (15.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
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| Disturbance In Attention | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA (15.0) | Systematic Assessment |
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| Dysuria | Renal and urinary disorders | MedDRA (15.0) | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Throat Irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Dry Throat | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15.0) | Systematic Assessment |
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After completion of the study, the Investigator may prepare a joint publication with the Sponsor. The Investigator must undertake not to submit any part of the individual data from this protocol for publication without prior consent of the Sponsor at a mutually agreed time.
| Day 1 ADA positive and cross-reactive with IL-8 |
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| Day 1 Pre-existing IL-8 autoantibodies |
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| Day 15 ADA positive |
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| Day 15 ADA positive and cross-reactive with IL-8 |
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| Day 15 Pre-existing IL-8 autoantibodies |
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| Day 29 ADA positive |
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| Day 29 ADA positive and cross-reactive with IL-8 |
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| Day 29 Pre-existing IL-8 autoantibodies |
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