Trial Outcomes & Findings for Alpha-1-Antitrypsin (AAT) To Treat Emphysema In AAT-Deficient Patients (EXACTLE) (NCT NCT00263887)
NCT ID: NCT00263887
Last Updated: 2014-08-21
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
77 participants
Primary outcome timeframe
24 or 30 months
Results posted on
2014-08-21
Participant Flow
Multicenter study with 3 sites in Denmark, Sweden, and the United Kingdom.
Participant milestones
| Measure |
Prolastin (60 mg/kg Body Weight)
|
Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
38
|
39
|
|
Overall Study
COMPLETED
|
35
|
32
|
|
Overall Study
NOT COMPLETED
|
3
|
7
|
Reasons for withdrawal
| Measure |
Prolastin (60 mg/kg Body Weight)
|
Placebo
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
|
Overall Study
Lung transplantation
|
1
|
2
|
|
Overall Study
Too ill to attend visit
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Disease progression
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
Baseline Characteristics
Alpha-1-Antitrypsin (AAT) To Treat Emphysema In AAT-Deficient Patients (EXACTLE)
Baseline characteristics by cohort
| Measure |
Prolastin (60 mg/kg Body Weight)
n=38 Participants
|
Placebo
n=39 Participants
|
Total
n=77 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
33 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Age, Continuous
|
54.68 years
STANDARD_DEVIATION 8.29 • n=5 Participants
|
55.26 years
STANDARD_DEVIATION 9.68 • n=7 Participants
|
54.97 years
STANDARD_DEVIATION 9.03 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
18 participants
n=5 Participants
|
17 participants
n=7 Participants
|
35 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
12 participants
n=5 Participants
|
14 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
8 participants
n=5 Participants
|
8 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
Severity of COPD at baseline
None
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Severity of COPD at baseline
Mild
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Severity of COPD at baseline
Moderate
|
10 participants
n=5 Participants
|
8 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
Severity of COPD at baseline
Severe
|
19 participants
n=5 Participants
|
20 participants
n=7 Participants
|
39 participants
n=5 Participants
|
|
Severity of COPD at baseline
Very Severe
|
6 participants
n=5 Participants
|
7 participants
n=7 Participants
|
13 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 24 or 30 monthsPopulation: The modified Intent-To-Treat Population was defined as all subjects in the Intent-To-Treat (ITT) Population (all randomized subjects) who had a valid baseline CT scan and at least one valid post-baseline CT scan measurement.
Outcome measures
| Measure |
Prolastin (60 mg/kg Body Weight)
n=35 Participants
|
Placebo
n=32 Participants
|
|---|---|---|
|
The Progression Rate of Emphysema Determined by Change in 15th Percentile of Lung Density Measured by Annual CT Scan of the Whole Lung
Baseline
|
47.980 g/L
Standard Deviation 19.072
|
45.477 g/L
Standard Deviation 16.949
|
|
The Progression Rate of Emphysema Determined by Change in 15th Percentile of Lung Density Measured by Annual CT Scan of the Whole Lung
Endpoint
|
45.085 g/L
Standard Deviation 19.433
|
41.354 g/L
Standard Deviation 16.260
|
|
The Progression Rate of Emphysema Determined by Change in 15th Percentile of Lung Density Measured by Annual CT Scan of the Whole Lung
Change from Baseline
|
-2.895 g/L
Standard Deviation 4.739
|
-4.124 g/L
Standard Deviation 4.147
|
SECONDARY outcome
Timeframe: 24 or 30 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 or 30 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 or 30 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 or 30 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 or 30 monthsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 24 or 30 monthsOutcome measures
Outcome data not reported
Adverse Events
Prolastin (60 mg/kg Body Weight)
Serious events: 9 serious events
Other events: 37 other events
Deaths: 0 deaths
Placebo
Serious events: 15 serious events
Other events: 38 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Prolastin (60 mg/kg Body Weight)
n=38 participants at risk
|
Placebo
n=39 participants at risk
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
5.3%
2/38
|
0.00%
0/39
|
|
Gastrointestinal disorders
Constipation
|
2.6%
1/38
|
0.00%
0/39
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
2.6%
1/38
|
0.00%
0/39
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/38
|
2.6%
1/39
|
|
Gastrointestinal disorders
Intra-abdominal haemorrhage
|
0.00%
0/38
|
2.6%
1/39
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/38
|
2.6%
1/39
|
|
General disorders
Nodule
|
0.00%
0/38
|
2.6%
1/39
|
|
Hepatobiliary disorders
Biliary colic
|
2.6%
1/38
|
0.00%
0/39
|
|
Hepatobiliary disorders
Gallbladder disorder
|
2.6%
1/38
|
2.6%
1/39
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.00%
0/38
|
2.6%
1/39
|
|
Infections and infestations
Pneumonia
|
7.9%
3/38
|
10.3%
4/39
|
|
Infections and infestations
Malaria
|
2.6%
1/38
|
0.00%
0/39
|
|
Infections and infestations
Appendicitis
|
0.00%
0/38
|
2.6%
1/39
|
|
Infections and infestations
Sepsis
|
0.00%
0/38
|
2.6%
1/39
|
|
Infections and infestations
Subcutaneous abscess
|
0.00%
0/38
|
2.6%
1/39
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/38
|
2.6%
1/39
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
2.6%
1/38
|
0.00%
0/39
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/38
|
2.6%
1/39
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/38
|
2.6%
1/39
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/38
|
2.6%
1/39
|
|
Nervous system disorders
Transient ischaemic attack
|
2.6%
1/38
|
0.00%
0/39
|
|
Reproductive system and breast disorders
Menorrhagia
|
2.6%
1/38
|
0.00%
0/39
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
5.3%
2/38
|
0.00%
0/39
|
|
Respiratory, thoracic and mediastinal disorders
Epixtaxis
|
2.6%
1/38
|
0.00%
0/39
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/38
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/38
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/38
|
2.6%
1/39
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/38
|
5.1%
2/39
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/38
|
2.6%
1/39
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
2.6%
1/38
|
0.00%
0/39
|
|
Skin and subcutaneous tissue disorders
Lichen sclerosus
|
0.00%
0/38
|
2.6%
1/39
|
Other adverse events
| Measure |
Prolastin (60 mg/kg Body Weight)
n=38 participants at risk
|
Placebo
n=39 participants at risk
|
|---|---|---|
|
Cardiac disorders
Angina pectoris
|
5.3%
2/38
|
2.6%
1/39
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/38
|
5.1%
2/39
|
|
Gastrointestinal disorders
Abdominal pain upper
|
7.9%
3/38
|
10.3%
4/39
|
|
Gastrointestinal disorders
Diarrhoea
|
7.9%
3/38
|
12.8%
5/39
|
|
Gastrointestinal disorders
Mouth ulceration
|
5.3%
2/38
|
0.00%
0/39
|
|
Gastrointestinal disorders
Nausea
|
5.3%
2/38
|
10.3%
4/39
|
|
Gastrointestinal disorders
Abdominal pain
|
2.6%
1/38
|
10.3%
4/39
|
|
Gastrointestinal disorders
Gastritis
|
2.6%
1/38
|
7.7%
3/39
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/38
|
10.3%
4/39
|
|
General disorders
Pyrexia
|
7.9%
3/38
|
5.1%
2/39
|
|
General disorders
Chest pain
|
5.3%
2/38
|
12.8%
5/39
|
|
General disorders
Infusion related reaction
|
5.3%
2/38
|
0.00%
0/39
|
|
General disorders
Oedema
|
2.6%
1/38
|
5.1%
2/39
|
|
General disorders
Oedema peripheral
|
2.6%
1/38
|
12.8%
5/39
|
|
General disorders
Asthenia
|
0.00%
0/38
|
5.1%
2/39
|
|
General disorders
Fatigue
|
0.00%
0/38
|
10.3%
4/39
|
|
Immune system disorders
Drug hypersensitivity
|
5.3%
2/38
|
0.00%
0/39
|
|
Immune system disorders
Hypersensitivity
|
5.3%
2/38
|
2.6%
1/39
|
|
Immune system disorders
Seasonal allergy
|
5.3%
2/38
|
2.6%
1/39
|
|
Infections and infestations
Nasopharyngitis
|
63.2%
24/38
|
56.4%
22/39
|
|
Infections and infestations
Pneumonia
|
31.6%
12/38
|
23.1%
9/39
|
|
Infections and infestations
Sinusitis
|
13.2%
5/38
|
12.8%
5/39
|
|
Infections and infestations
Influenza
|
10.5%
4/38
|
7.7%
3/39
|
|
Infections and infestations
Tooth abscess
|
7.9%
3/38
|
12.8%
5/39
|
|
Infections and infestations
Bronchitis
|
5.3%
2/38
|
2.6%
1/39
|
|
Infections and infestations
Localised infection
|
5.3%
2/38
|
2.6%
1/39
|
|
Infections and infestations
Oral candidiasis
|
5.3%
2/38
|
5.1%
2/39
|
|
Infections and infestations
Urinary tract infection
|
5.3%
2/38
|
5.1%
2/39
|
|
Infections and infestations
Gastroenteritis
|
2.6%
1/38
|
7.7%
3/39
|
|
Infections and infestations
Eye infection
|
0.00%
0/38
|
5.1%
2/39
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/38
|
5.1%
2/39
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/38
|
5.1%
2/39
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/38
|
5.1%
2/39
|
|
Infections and infestations
Tooth infection
|
0.00%
0/38
|
5.1%
2/39
|
|
Infections and infestations
Viral infection
|
0.00%
0/38
|
5.1%
2/39
|
|
Injury, poisoning and procedural complications
Fall
|
5.3%
2/38
|
0.00%
0/39
|
|
Injury, poisoning and procedural complications
Contusion
|
2.6%
1/38
|
12.8%
5/39
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.00%
0/38
|
5.1%
2/39
|
|
Investigations
Blood potassium decreased
|
5.3%
2/38
|
2.6%
1/39
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.2%
5/38
|
5.1%
2/39
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.9%
3/38
|
12.8%
5/39
|
|
Musculoskeletal and connective tissue disorders
Monoarthritis
|
5.3%
2/38
|
0.00%
0/39
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.3%
2/38
|
5.1%
2/39
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.3%
2/38
|
15.4%
6/39
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.6%
1/38
|
10.3%
4/39
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.00%
0/38
|
5.1%
2/39
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/38
|
5.1%
2/39
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
5.3%
2/38
|
2.6%
1/39
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
|
2.6%
1/38
|
5.1%
2/39
|
|
Nervous system disorders
Headache
|
23.7%
9/38
|
25.6%
10/39
|
|
Nervous system disorders
Dizziness
|
2.6%
1/38
|
5.1%
2/39
|
|
Nervous system disorders
Syncope
|
2.6%
1/38
|
5.1%
2/39
|
|
Nervous system disorders
Sinus headache
|
0.00%
0/38
|
5.1%
2/39
|
|
Psychiatric disorders
Insomnia
|
5.3%
2/38
|
0.00%
0/39
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
21.1%
8/38
|
7.7%
3/39
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
7.9%
3/38
|
5.1%
2/39
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.6%
1/38
|
12.8%
5/39
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
2.6%
1/38
|
5.1%
2/39
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.6%
1/38
|
5.1%
2/39
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/38
|
5.1%
2/39
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.9%
3/38
|
2.6%
1/39
|
|
Vascular disorders
Hypertension
|
5.3%
2/38
|
5.1%
2/39
|
|
Vascular disorders
Phlebitis
|
0.00%
0/38
|
5.1%
2/39
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator must send a draft manuscript of the publication or abstract to the sponsor thirty days in advance of submission in order to obtain approval prior to submission of the final version for publication. This will be reviewed within thirty days and approval will not be withheld unreasonably. In case of a difference of opinion between the sponsor and the investigator(s), the contents of the publication will be discussed in order to find a solution, which satisfies both parties.
- Publication restrictions are in place
Restriction type: OTHER