Trial Outcomes & Findings for Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency (NCT NCT01213043)

NCT ID: NCT01213043

Last Updated: 2013-05-20

Results Overview

Number of subjects experiencing at least one TEAE. TEAEs were defined as any adverse event (AE) during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: 22 weeks
• Results posted on: 2013-05-20

Participant Flow

Subjects entered a Screening Phase (up to 21 days in duration) to determine subject eligibility and for wash-out of prior alpha1-PI augmentation therapy, if applicable, prior to randomization to one of two treatment sequences.

Participant milestones

Measure	60 mg/kg - 120 mg/kg Prolastin-C Treatment Sequence Weekly infusions of 60 mg/kg Prolastin-C for 8 weeks followed by a 2-week off-treatment washout period followed by weekly infusions of 120 mg/kg Prolastin-C for 8 weeks (total of 16 treatment weeks)	120 mg/kg - 60 mg/kg Prolastin-C Treatment Sequence Weekly infusions of 120 mg/kg Prolastin-C for 8 weeks followed by a 2-week off-treatment washout period followed by weekly infusions of 60 mg/kg Prolastin-C for 8 weeks (total of 16 treatment weeks)
Treatment Period 1 STARTED	15	15
Treatment Period 1 COMPLETED	15	15
Treatment Period 1 NOT COMPLETED	0	0
Washout Period STARTED	15	15
Washout Period COMPLETED	15	15
Washout Period NOT COMPLETED	0	0
Treatment Period 2 STARTED	15	15
Treatment Period 2 COMPLETED	15	15
Treatment Period 2 NOT COMPLETED	0	0
Follow-up STARTED	15	15
Follow-up COMPLETED	15	15
Follow-up NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Pharmacokinetics of Alpha-1 Proteinase Inhibitor in Subjects With Alpha1-Antitrypsin Deficiency

Baseline characteristics by cohort

Measure	60 mg/kg - 120 mg/kg Prolastin-C Treatment Sequence n=15 Participants Weekly infusions of 60 mg/kg Prolastin-C for 8 weeks followed by a 2-week off-treatment washout period followed by weekly infusions of 120 mg/kg Prolastin-C for 8 weeks (total of 16 treatment weeks)	120 mg/kg - 60 mg/kg Prolastin-C Treatment Sequence n=15 Participants Weekly infusions of 120 mg/kg Prolastin-C for 8 weeks followed by a 2-week off-treatment washout period followed by weekly infusions of 60 mg/kg Prolastin-C for 8 weeks (total of 16 treatment weeks)	Total n=30 Participants Total of all reporting groups
Age Continuous	59.7 years STANDARD_DEVIATION 6.89 • n=5 Participants	57.4 years STANDARD_DEVIATION 6.34 • n=7 Participants	58.6 years STANDARD_DEVIATION 6.62 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 22 weeks

Population: All safety analyses were performed on the safety population, which comprised of all subjects who were randomized and received at least one dose of investigational product (Prolastin-C).

Number of subjects experiencing at least one TEAE. TEAEs were defined as any adverse event (AE) during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).

Outcome measures

Measure	60 mg/kg Prolastin-C n=30 Participants	120 mg/kg Prolastin-C n=30 Participants
Subjects With Treatment-Emergent Adverse Events (TEAEs)	23 participants	18 participants

PRIMARY outcome

Timeframe: 22 weeks

Population: All safety analyses were performed on the safety population, which comprised of all subjects who were randomized and received at least one dose of investigational product (Prolastin-C).

Number of subjects with at least one TEAE that was determined by the Investigator to be either "possibly related" or "related" to the investigational product (i.e., Prolastin-C).

Outcome measures

Measure	60 mg/kg Prolastin-C n=30 Participants	120 mg/kg Prolastin-C n=30 Participants
Subjects With Drug-Related TEAE(s)	3 participants	1 participants

PRIMARY outcome

Timeframe: 22 weeks

Population: All safety analyses were performed on the safety population, which comprised of all subjects who were randomized and received at least one dose of investigational product (Prolastin-C).

Number of subjects who experienced at least one treatment-emergent SAE.

Outcome measures

Measure	60 mg/kg Prolastin-C n=30 Participants	120 mg/kg Prolastin-C n=30 Participants
Subjects With Treatment-Emergent Serious Adverse Events (SAEs)	0 participants	0 participants

PRIMARY outcome

Timeframe: 22 weeks

Population: All safety analyses were performed on the safety population, which comprised of all subjects who were randomized and received at least one dose of investigational product (Prolastin-C).

Number of subjects who were withdrawn from the study due to at least one AE.

Outcome measures

Measure	60 mg/kg Prolastin-C n=30 Participants	120 mg/kg Prolastin-C n=30 Participants
Subjects Withdrawn Due to an AE(s)	0 participants	0 participants

PRIMARY outcome

Timeframe: 22 weeks

Population: All safety analyses were performed on the safety population, which comprised of all subjects who were randomized and received at least one dose of investigational product (Prolastin-C).

Number of subjects with at least one treatment-emergent pulmonary exacerbation

Outcome measures

Measure	60 mg/kg Prolastin-C n=30 Participants	120 mg/kg Prolastin-C n=30 Participants
Subjects With Treatment-Emergent Pulmonary Exacerbation(s)	7 participants	5 participants

PRIMARY outcome

Timeframe: 22 weeks

Population: All safety analyses were performed on the safety population, which comprised of all subjects who were randomized and received at least one dose of investigational product (Prolastin-C).

Number of subjects who experienced at least one severe TEAE or pulmonary exacerbation.

Outcome measures

Measure	60 mg/kg Prolastin-C n=30 Participants	120 mg/kg Prolastin-C n=30 Participants
Subjects With Severe TEAE(s) or Pulmonary Exacerbation(s)	0 participants	0 participants

PRIMARY outcome

Timeframe: 22 Weeks

Population: All safety analyses were performed on the safety population, which comprised of all subjects who were randomized and received at least one dose of investigational product (Prolastin-C).

Total number of TEAEs reported.

Outcome measures

Measure	60 mg/kg Prolastin-C n=30 Participants	120 mg/kg Prolastin-C n=30 Participants
Number of TEAEs	69 Events	43 Events

PRIMARY outcome

Timeframe: 22 Weeks

Population: All safety analyses were performed on the safety population, which comprised of all subjects who were randomized and received at least one dose of investigational product (Prolastin-C).

Total number of drug-related TEAEs reported

Outcome measures

Measure	60 mg/kg Prolastin-C n=30 Participants	120 mg/kg Prolastin-C n=30 Participants
Number of Drug-related TEAEs	5 Events	1 Events

PRIMARY outcome

Timeframe: 22 Weeks

Population: All safety analyses were performed on the safety population, which comprised of all subjects who were randomized and received at least one dose of investigational product (Prolastin-C).

Total number of treatment-emergent pulmonary exacerbations.

Outcome measures

Measure	60 mg/kg Prolastin-C n=30 Participants	120 mg/kg Prolastin-C n=30 Participants
Number of Treatment-Emergent Pulmonary Exacerbations	9 Events	6 Events

SECONDARY outcome

Timeframe: Week 8 and Week 18 at the following timepoints: 0 (pre-infusion), completion of first infusion bag, completion of 2nd infusion bag, and 15 min, 30 min, and 1, 2, 4, 8, 24, 48, 120, and 168 hours post-dose

Population: Pharmacokinetic (PK) Population, which consisted of all subjects who received investigational product (Prolastin-C) and had sufficient and valid serum concentration data to facilitate calculation of PK parameters.

Area Under the Alpha-1 PI Concentration-Time Curve from Day 0 to Day 7

Outcome measures

Measure	60 mg/kg Prolastin-C n=29 Participants	120 mg/kg Prolastin-C n=30 Participants
AUC0-7days	203.6 h*mg/mL Standard Deviation 20.48	344.8 h*mg/mL Standard Deviation 46.53

SECONDARY outcome

Timeframe: Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19

Population: PK Population, which consisted of all subjects who received investigational product (Prolastin-C) and had sufficient and valid serum concentration data to facilitate calculation of PK parameters.

The average trough concentration at steady-state, calculated as the mean value using the four Trough measurements obtained at Weeks 6, 7, 8 and at 7 days (168 hours) post infusion at Week 8 for the first treatment period or prior to the start of the infusions at Weeks 16, 17, 18, and at 7 days (168 hours) post infusion at Week 18 for the second treatment period.

Outcome measures

Measure	60 mg/kg Prolastin-C n=30 Participants	120 mg/kg Prolastin-C n=30 Participants
Mean Trough	17.3 μM Standard Deviation 2.36	27.7 μM Standard Deviation 3.75

Adverse Events

60 mg/kg Prolastin-C

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

120 mg/kg Prolastin-C

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	60 mg/kg Prolastin-C n=30 participants at risk	120 mg/kg Prolastin-C n=30 participants at risk
Respiratory, thoracic and mediastinal disorders COPD Exacerbation	23.3% 7/30 • Number of events 9 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).	16.7% 5/30 • Number of events 6 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).
Infections and infestations Urinary Tract Infection	10.0% 3/30 • Number of events 4 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).	0.00% 0/30 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).
Injury, poisoning and procedural complications Contusion	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).	6.7% 2/30 • Number of events 2 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).
Blood and lymphatic system disorders Thrombocytopenia	6.7% 2/30 • Number of events 2 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).	0.00% 0/30 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).
Renal and urinary disorders Proteinuria	6.7% 2/30 • Number of events 2 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).	3.3% 1/30 • Number of events 1 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).
Investigations Blood Creatinine Increased	0.00% 0/30 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).	6.7% 2/30 • Number of events 2 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).
Investigations Blood Glucose Increased	0.00% 0/30 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).	6.7% 2/30 • Number of events 2 • Adverse events were assessed from the time of informed consent through the end of study visit; thus, AEs were assessed for up to 25 weeks. Assessment of AEs were performed by questioning the subject at each scheduled study visit. Treatment Emergent adverse events were defined as any AE during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).

Additional Information

Benjamin King, PhD

Grifols Therapeutics Inc.

Email: ben.king@grifols.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER