Trial Outcomes & Findings for Safety & Efficacy Study of rAAV1-CB-hAAT for Alpha-1 Antitrypsin Deficiency (NCT NCT01054339)
NCT ID: NCT01054339
Last Updated: 2019-03-28
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
9 participants
Primary outcome timeframe
During 1 year after study agent administration
Results posted on
2019-03-28
Participant Flow
Subjects were recruited from two clinical trial sites (University of Massachusetts Medical Center and Cincinnati Children's Hospital Medical Center).
Participant milestones
| Measure |
Low Dose
rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site
|
Middle Dose
rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as 32 IM injections distributed across three muscle sites
|
High Dose
rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as 100 IM injections distributed across 10 muscle sites
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety & Efficacy Study of rAAV1-CB-hAAT for Alpha-1 Antitrypsin Deficiency
Baseline characteristics by cohort
| Measure |
Low Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site
|
Middle Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as 32 IM injections distributed across three muscle sites
|
High Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as 100 IM injections distributed across 10 muscle sites
|
Total
n=9 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
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Age, Continuous
|
50.3 years
STANDARD_DEVIATION 26.4 • n=5 Participants
|
48.7 years
STANDARD_DEVIATION 9.3 • n=7 Participants
|
54.3 years
STANDARD_DEVIATION 3.5 • n=5 Participants
|
51.1 years
STANDARD_DEVIATION 14.3 • n=4 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Alpha-1 antitrypsin phenotype
ZZ
|
2 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
8 participants
n=4 Participants
|
|
Alpha-1 antitrypsin phenotype
SZ
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
|
Serum total alpha-1 antitrypsin concentration
|
6.56 microMolar
STANDARD_DEVIATION 2.00 • n=5 Participants
|
3.54 microMolar
STANDARD_DEVIATION 0.12 • n=7 Participants
|
3.45 microMolar
STANDARD_DEVIATION 0.25 • n=5 Participants
|
4.31 microMolar
STANDARD_DEVIATION 1.88 • n=4 Participants
|
PRIMARY outcome
Timeframe: During 1 year after study agent administrationPopulation: Analysis based on all subjects enrolled in study.
Outcome measures
| Measure |
Low Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site
|
Middle Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as a total of 32 IM injections distributed across three muscle sites
|
High Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as100 IM injections distributed across 10 muscle sites
|
|---|---|---|---|
|
Frequency of Grade 3 or 4 Adverse Events
|
0 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: During months 6-12 after study agent adminsitrationPopulation: One subject in low dose group had AAT phenotype SZ, which made measurement of M-specific serum alpha-1 antitrypsin concentration invalid.
Results are the mean ± SD for pre-treatment (Screening and Baseline) and Months 6-12 values and mean ± SE for the difference between the pre-treatment and months 6-12 means for 2 subjects in the low dose group and 3 subjects in each of the other two groups. The monoclonal antibody used to determine serum M-specific AAT concentrations has very little cross-reactivity with Z type AAT but cross-reacts strongly with S type AAT, causing results for this assay to be spuriously high for subject 303 in the low dose group.
Outcome measures
| Measure |
Low Dose
n=2 Participants
rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site
|
Middle Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as a total of 32 IM injections distributed across three muscle sites
|
High Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as100 IM injections distributed across 10 muscle sites
|
|---|---|---|---|
|
Changes in Serum M-specific Alpha-1 Antitrypsin Concentration
|
31.5 nanomolar
Standard Error 7.56
|
71.8 nanomolar
Standard Error 22.73
|
239.2 nanomolar
Standard Error 27.57
|
SECONDARY outcome
Timeframe: During months 6-12 after study agent adminstrationPopulation: Analysis based on all subjects enrolled in study.
Results are the mean ± SD for pre-treatment (Screening and Baseline) and Months 6-12 data and mean ± SE for the difference between the pre-treatment and months 6-12 means for 3 subjects per group.
Outcome measures
| Measure |
Low Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site
|
Middle Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as a total of 32 IM injections distributed across three muscle sites
|
High Dose
n=3 Participants
rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as100 IM injections distributed across 10 muscle sites
|
|---|---|---|---|
|
Changes in Serum Total Alpha-1 Antitrypsin Concentrations
|
0.33 micromolar
Standard Error 1.14
|
0.16 micromolar
Standard Error 0.10
|
0.19 micromolar
Standard Error 0.16
|
Adverse Events
Low Dose
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Middle Dose
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
High Dose
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Low Dose
n=3 participants at risk
rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site
|
Middle Dose
n=3 participants at risk
rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as 32 IM injections distributed across three muscle sites
|
High Dose
n=3 participants at risk
rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as 100 IM injections distributed across 10 muscle sites
|
|---|---|---|---|
|
Gastrointestinal disorders
diverticulitis
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
Other adverse events
| Measure |
Low Dose
n=3 participants at risk
rAAV1-CB-hAAT at dosage level of 6 x 10e11 vg/kg administered as 10 IM injections distributed across a single muscle site
|
Middle Dose
n=3 participants at risk
rAAV1-CB-hAAT at dosage level of 1.9 x 10e12 vg/kg administered as 32 IM injections distributed across three muscle sites
|
High Dose
n=3 participants at risk
rAAV1-CB-hAAT at dosage level of 6 x 10e12 vg/kg administered as 100 IM injections distributed across 10 muscle sites
|
|---|---|---|---|
|
General disorders
Injection site discomfort
|
66.7%
2/3 • Number of events 2 • 1 year
|
66.7%
2/3 • Number of events 2 • 1 year
|
66.7%
2/3 • Number of events 2 • 1 year
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
100.0%
3/3 • Number of events 3 • 1 year
|
|
Infections and infestations
Ear infection
|
33.3%
1/3 • Number of events 1 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Vascular disorders
Ecchymosis
|
33.3%
1/3 • Number of events 1 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • 1 year
|
66.7%
2/3 • Number of events 2 • 1 year
|
0.00%
0/3 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/3 • 1 year
|
66.7%
2/3 • Number of events 2 • 1 year
|
0.00%
0/3 • 1 year
|
|
Vascular disorders
Phlebitis superficial
|
33.3%
1/3 • Number of events 1 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
66.7%
2/3 • Number of events 2 • 1 year
|
|
General disorders
Influenza-like illness
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
General disorders
Injection site atrophy
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
General disorders
Injection site erythema
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
General disorders
Injection site pain
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
General disorders
Malaise
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Muscle strain
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Muscle twitching
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
General disorders
Post-procedural discomfort
|
66.7%
2/3 • Number of events 2 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Blood and lymphatic system disorders
Lymphadenopath
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Gastrointestinal disorders
Diverticulosis
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Bone lesion
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Limb discomfort
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Myalgias
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Nervous system disorders
Anosmia
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Psychiatric disorders
Anxiety
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Chest pain
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea exertional
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Infective exacerbation of chronic obstructive pulmonary diseases
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Lung neoplasm
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Sinus headache
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Skin and subcutaneous tissue disorders
Furuncle
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Skin and subcutaneous tissue disorders
Skin hemorrhage
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Vascular disorders
Aortic Aneurysm
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Vascular disorders
Postmastectomy lymphedema syndrome
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
General disorders
Injection site hemorrhage
|
33.3%
1/3 • Number of events 1 • 1 year
|
100.0%
3/3 • Number of events 3 • 1 year
|
100.0%
3/3 • Number of events 3 • 1 year
|
|
General disorders
Pyrexia
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Infections and infestations
Bronchitis
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Gastrointestinal disorders
Gastroenteritis viral
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Infections and infestations
Gingival abscess
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Infections and infestations
Oral candidiasis
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Infections and infestations
Sinusitis
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Injury, poisoning and procedural complications
Post procedural edema
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Injury, poisoning and procedural complications
Post procedural hematoma
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
0.00%
0/3 • 1 year
|
|
Injury, poisoning and procedural complications
Procedural pain
|
100.0%
3/3 • Number of events 3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/3 • 1 year
|
33.3%
1/3 • Number of events 1 • 1 year
|
0.00%
0/3 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60