Trial Outcomes & Findings for This Study is Designed to Evaluate PD/PK and Safety of Replagal Manufactured by Two Different Processes. (NCT NCT01304277)
NCT ID: NCT01304277
Last Updated: 2021-07-19
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
17 participants
Primary outcome timeframe
Baseline to EOS
Results posted on
2021-07-19
Participant Flow
The first patient participated in the study on 06 December 2011 and the last patient completed the study procedures on 28 December 2012.
Participant milestones
| Measure |
Replagal® (0.2 mg/kg, EOW)
Patients who had received Replagal RB for at least 26 weeks prior to entering the study REP-082, received 1 dose of Replagal RB at baseline before switching to Replagal AF. They then received 14 weeks of treatment with Replagal AF.
|
|---|---|
|
Screening (Replagal RB, Week 0- Week 2)
STARTED
|
17
|
|
Screening (Replagal RB, Week 0- Week 2)
COMPLETED
|
17
|
|
Screening (Replagal RB, Week 0- Week 2)
NOT COMPLETED
|
0
|
|
Treatment (Replagal AF, Week 2- EOS)
STARTED
|
17
|
|
Treatment (Replagal AF, Week 2- EOS)
COMPLETED
|
17
|
|
Treatment (Replagal AF, Week 2- EOS)
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
This Study is Designed to Evaluate PD/PK and Safety of Replagal Manufactured by Two Different Processes.
Baseline characteristics by cohort
| Measure |
Replagal® (0.2 mg/kg, EOW)
n=17 Participants
Patients who had received Replagal RB for at least 26 weeks prior to entering the study REP-082, received 1 dose of Replagal RB at baseline before switching to Replagal AF. They then received 14 weeks of treatment with Replagal AF.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
39.8 Years
STANDARD_DEVIATION 13.589 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
|
Region of Enrollment
CANADA
|
17 Participants
n=5 Participants
|
|
Study Specific Characteristic [Urine Gb3]
|
919.27 nmol/g creatinine
STANDARD_DEVIATION 990.144 • n=5 Participants
|
|
Study Specific Characteristic [Plasma Gb3]
|
5.276 nmol/mL
STANDARD_DEVIATION 1.562 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to EOSOutcome measures
| Measure |
Replagal® (0.2 mg/kg, EOW)
n=17 Participants
Patients who had received Replagal RB for at least 26 weeks prior to entering the study REP-082, received 1 dose of Replagal RB at baseline before switching to Replagal AF. They then received 14 weeks of treatment with Replagal AF.
|
Replagal AF
Patients received 7 EOW infusions of treatment with Replagal AF from week 2 to week 14 in REP-082.
|
Overall
Overall number of patients who experienced adverse events during the course of REP-082 study.
|
|---|---|---|---|
|
Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels
|
-28.68 (nmol/g creatinine)
Standard Deviation 192.659
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to EOSOutcome measures
| Measure |
Replagal® (0.2 mg/kg, EOW)
n=17 Participants
Patients who had received Replagal RB for at least 26 weeks prior to entering the study REP-082, received 1 dose of Replagal RB at baseline before switching to Replagal AF. They then received 14 weeks of treatment with Replagal AF.
|
Replagal AF
Patients received 7 EOW infusions of treatment with Replagal AF from week 2 to week 14 in REP-082.
|
Overall
Overall number of patients who experienced adverse events during the course of REP-082 study.
|
|---|---|---|---|
|
Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels
|
0.170 (nmol/mL)
Standard Deviation 0.503
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 0 to Week 14The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg, EOW)
n=17 Participants
Patients who had received Replagal RB for at least 26 weeks prior to entering the study REP-082, received 1 dose of Replagal RB at baseline before switching to Replagal AF. They then received 14 weeks of treatment with Replagal AF.
|
Replagal AF
Patients received 7 EOW infusions of treatment with Replagal AF from week 2 to week 14 in REP-082.
|
Overall
Overall number of patients who experienced adverse events during the course of REP-082 study.
|
|---|---|---|---|
|
Dose-normalized Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast/Dose)
Week 14 versus 0
|
0.65 Ratio
Interval 0.61 to 0.72
|
—
|
—
|
|
Dose-normalized Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast/Dose)
Week 14 versus 2
|
1.05 Ratio
Interval 0.94 to 1.23
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 0 to Week 14The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg, EOW)
n=17 Participants
Patients who had received Replagal RB for at least 26 weeks prior to entering the study REP-082, received 1 dose of Replagal RB at baseline before switching to Replagal AF. They then received 14 weeks of treatment with Replagal AF.
|
Replagal AF
Patients received 7 EOW infusions of treatment with Replagal AF from week 2 to week 14 in REP-082.
|
Overall
Overall number of patients who experienced adverse events during the course of REP-082 study.
|
|---|---|---|---|
|
Dose-normalized AUC Extrapolated to Infinity (AUC∞/Dose)
Week 14 versus 0
|
0.67 Ratio
Interval 0.62 to 0.75
|
—
|
—
|
|
Dose-normalized AUC Extrapolated to Infinity (AUC∞/Dose)
Week 14 versus 2
|
1.07 Ratio
Interval 0.97 to 1.26
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 0 to Week 14The dose-normalized calculation was performed by dividing the pharmacokinetic parameter by the administered dose.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg, EOW)
n=17 Participants
Patients who had received Replagal RB for at least 26 weeks prior to entering the study REP-082, received 1 dose of Replagal RB at baseline before switching to Replagal AF. They then received 14 weeks of treatment with Replagal AF.
|
Replagal AF
Patients received 7 EOW infusions of treatment with Replagal AF from week 2 to week 14 in REP-082.
|
Overall
Overall number of patients who experienced adverse events during the course of REP-082 study.
|
|---|---|---|---|
|
Dose-normalized Maximum Serum Concentration (Cmax/Dose)
Week 14 versus 0
|
0.81 Ratio
Interval 0.76 to 0.91
|
—
|
—
|
|
Dose-normalized Maximum Serum Concentration (Cmax/Dose)
Week 14 versus 2
|
1.05 Ratio
Interval 0.96 to 1.21
|
—
|
—
|
SECONDARY outcome
Timeframe: EOSOutcome measures
| Measure |
Replagal® (0.2 mg/kg, EOW)
n=17 Participants
Patients who had received Replagal RB for at least 26 weeks prior to entering the study REP-082, received 1 dose of Replagal RB at baseline before switching to Replagal AF. They then received 14 weeks of treatment with Replagal AF.
|
Replagal AF
Patients received 7 EOW infusions of treatment with Replagal AF from week 2 to week 14 in REP-082.
|
Overall
Overall number of patients who experienced adverse events during the course of REP-082 study.
|
|---|---|---|---|
|
To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study
Anti-Agalsidase alfa Antibody Negative
|
13 participants
|
—
|
—
|
|
To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study
Anti-Agalsidase alfa Antibody Positive (IgG)
|
2 participants
|
—
|
—
|
|
To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study
Anti-Agalsidase alfa Antibody Positive (IgM)
|
2 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Week 2 to EOSTo Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status, concomitant medication, vital signs and ECG.
Outcome measures
| Measure |
Replagal® (0.2 mg/kg, EOW)
n=17 Participants
Patients who had received Replagal RB for at least 26 weeks prior to entering the study REP-082, received 1 dose of Replagal RB at baseline before switching to Replagal AF. They then received 14 weeks of treatment with Replagal AF.
|
Replagal AF
n=17 Participants
Patients received 7 EOW infusions of treatment with Replagal AF from week 2 to week 14 in REP-082.
|
Overall
n=17 Participants
Overall number of patients who experienced adverse events during the course of REP-082 study.
|
|---|---|---|---|
|
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
No TEAE
|
9 participants
|
5 participants
|
5 participants
|
|
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
Experienced at least one TEAE
|
8 participants
|
12 participants
|
12 participants
|
|
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
Deaths
|
0 participants
|
0 participants
|
0 participants
|
|
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
Discontinued due to a TEAE
|
0 participants
|
0 participants
|
0 participants
|
|
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
Experienced at least one drug-related TEAE
|
3 participants
|
3 participants
|
3 participants
|
|
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
Experienced at least one SAE
|
0 participants
|
2 participants
|
2 participants
|
|
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
At least one severe or life- threatening TEAE
|
1 participants
|
1 participants
|
1 participants
|
|
Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
At least one IRR (infusion related reaction)
|
1 participants
|
1 participants
|
1 participants
|
Adverse Events
Replagal® (0.2 mg/kg, IV, EOW)
Serious events: 2 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Replagal® (0.2 mg/kg, IV, EOW)
n=17 participants at risk
Overall patients that participated in REP-082
|
|---|---|
|
Cardiac disorders
Cardiac arrest
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Cardiac disorders
Ventricular fibrillation
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
Other adverse events
| Measure |
Replagal® (0.2 mg/kg, IV, EOW)
n=17 participants at risk
Overall patients that participated in REP-082
|
|---|---|
|
Cardiac disorders
Bradycardia
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Eye disorders
Visual impairment
|
5.9%
1/17 • Number of events 2 • Baseline to EOS
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Gastrointestinal disorders
Abdominal pain
|
11.8%
2/17 • Number of events 4 • Baseline to EOS
|
|
Gastrointestinal disorders
Constipation
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Gastrointestinal disorders
Diarrhoea
|
17.6%
3/17 • Number of events 5 • Baseline to EOS
|
|
Gastrointestinal disorders
Nausea
|
11.8%
2/17 • Number of events 5 • Baseline to EOS
|
|
Gastrointestinal disorders
Vomiting
|
11.8%
2/17 • Number of events 2 • Baseline to EOS
|
|
General disorders
Fatigue
|
17.6%
3/17 • Number of events 3 • Baseline to EOS
|
|
General disorders
Oedema peripheral
|
11.8%
2/17 • Number of events 3 • Baseline to EOS
|
|
General disorders
Pyrexia
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Infections and infestations
Gastroenteritis viral
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Infections and infestations
Nasopharyngitis
|
5.9%
1/17 • Number of events 3 • Baseline to EOS
|
|
Infections and infestations
Upper respiratory tract infection
|
11.8%
2/17 • Number of events 3 • Baseline to EOS
|
|
Injury, poisoning and procedural complications
Excoriation
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Injury, poisoning and procedural complications
Joint sprain
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Injury, poisoning and procedural complications
Procedural pain
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Investigations
Blood potassium decreased
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.8%
2/17 • Number of events 5 • Baseline to EOS
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Musculoskeletal and connective tissue disorders
Sensation of heaviness
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Nervous system disorders
Dizziness
|
11.8%
2/17 • Number of events 5 • Baseline to EOS
|
|
Nervous system disorders
Headache
|
11.8%
2/17 • Number of events 4 • Baseline to EOS
|
|
Nervous system disorders
Migraine
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Nervous system disorders
Paraesthesia
|
11.8%
2/17 • Number of events 7 • Baseline to EOS
|
|
Psychiatric disorders
Depression
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Psychiatric disorders
Stress
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Renal and urinary disorders
Haematuria
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Reproductive system and breast disorders
Gynaecomastia
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.9%
1/17 • Number of events 2 • Baseline to EOS
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
11.8%
2/17 • Number of events 2 • Baseline to EOS
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.9%
1/17 • Number of events 2 • Baseline to EOS
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.9%
1/17 • Number of events 1 • Baseline to EOS
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Shire's agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤180 days from the time submitted to Shire for review. Shire does not prohibit publication, but can require the removal of confidential information (excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial's multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER