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This Study is Designed to Evaluate PD/PK and Safety of Replagal Manufactured by Two Different Processes.

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ClinicalTrials.gov Identifier: NCT01304277
Recruitment Status : Completed
First Posted : February 25, 2011
Results First Posted : April 25, 2014
Last Update Posted : April 25, 2014
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label)
Condition Fabry Disease
Intervention Biological: agalsidase alfa
Enrollment 17
Recruitment Details The first patient participated in the study on 06 December 2011 and the last patient completed the study procedures on 28 December 2012.
Pre-assignment Details  
Arm/Group Title Replagal® (0.2 mg/kg, EOW)
Hide Arm/Group Description 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.
Period Title: Screening (Replagal RB, Week 0- Week 2)
Started 17
Completed 17
Not Completed 0
Period Title: Treatment (Replagal AF, Week 2- EOS)
Started 17
Completed 17
Not Completed 0
Arm/Group Title Replagal® (0.2 mg/kg, EOW)
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 17
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
<=18 years
0
   0.0%
Between 18 and 65 years
17
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants
39.8  (13.589)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
Female
0
   0.0%
Male
17
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
CANADA Number Analyzed 17 participants
17
Study Specific Characteristic [Urine Gb3]   [1] 
Mean (Standard Deviation)
Unit of measure:  Nmol/g creatinine
Number Analyzed 17 participants
919.27  (990.144)
[1]
Measure Description: Baseline is the average of Gb3 (globotriaosylceramide) levels on RB Replagal at screening, Week 0, and Week 2 prior to AF Replagal dosing.
Study Specific Characteristic [Plasma Gb3]   [1] 
Mean (Standard Deviation)
Unit of measure:  nmol/mL
Number Analyzed 17 participants
5.276  (1.562)
[1]
Measure Description: Baseline is the average of Gb3 (globotriaosylceramide) levels on RB Replagal at screening, Week 0, and Week 2 prior to AF Replagal dosing.
1.Primary Outcome
Title Change From Baseline to Week 16 (EOS) in Urine Gb3 Levels
Hide Description [Not Specified]
Time Frame Baseline to EOS
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Replagal® (0.2 mg/kg, EOW)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: (nmol/g creatinine)
-28.68  (192.659)
2.Secondary Outcome
Title Change From Baseline to Week 16 (EOS) in Plasma Gb3 Levels
Hide Description [Not Specified]
Time Frame Baseline to EOS
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Replagal® (0.2 mg/kg, EOW)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: (nmol/mL)
0.170  (0.503)
3.Secondary Outcome
Title Dose-normalized Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Sample (AUClast/Dose)
Hide Description [Not Specified]
Time Frame Week 0 to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Replagal® (0.2 mg/kg, EOW)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 17
Geometric Mean (90% Confidence Interval)
Unit of Measure: Ratio
Week 14 versus 0
0.65
(0.61 to 0.72)
Week 14 versus 2
1.05
(0.94 to 1.23)
4.Secondary Outcome
Title Dose-normalized AUC Extrapolated to Infinity (AUC∞/Dose)
Hide Description [Not Specified]
Time Frame Week 0 to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Replagal® (0.2 mg/kg, EOW)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 17
Geometric Mean (90% Confidence Interval)
Unit of Measure: Ratio
Week 14 versus 0
0.67
(0.62 to 0.75)
Week 14 versus 2
1.07
(0.97 to 1.26)
5.Secondary Outcome
Title Dose-normalized Maximum Serum Concentration (Cmax/Dose)
Hide Description [Not Specified]
Time Frame Week 0 to Week 14
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Replagal® (0.2 mg/kg, EOW)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 17
Geometric Mean (90% Confidence Interval)
Unit of Measure: Ratio
Week 14 versus 0
0.81
(0.76 to 0.91)
Week 14 versus 2
1.05
(0.96 to 1.21)
6.Secondary Outcome
Title To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status (in Serum) at End of Study
Hide Description [Not Specified]
Time Frame EOS
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Replagal® (0.2 mg/kg, EOW)
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: participants
Anti-Agalsidase alfa Antibody Negative 13
Anti-Agalsidase alfa Antibody Positive (IgG) 2
Anti-Agalsidase alfa Antibody Positive (IgM) 2
7.Secondary Outcome
Title Overall Summary of TEAEs by Treatment (Replagal RB and Replagal AF)
Hide Description To Assess Safety and Tolerability by Anti-agalsidase Alfa Antibody Status, concomitant medication, vital signs and ECG.
Time Frame Week 2 to EOS
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Replagal RB Replagal AF Overall
Hide Arm/Group Description:
Patients who had received Replagal RB for at least 26 weeks prior to entering the study REP-082.
Patients received 7 EOW infusions of treatment with Replagal AF from week 2 to week 14 in REP-082.
Overall number of patients who experienced adverse events during the course of REP-082 study.
Overall Number of Participants Analyzed 17 17 17
Measure Type: Number
Unit of Measure: participants
No TEAE 9 5 5
Experienced at least one TEAE 8 12 12
Deaths 0 0 0
Discontinued due to a TEAE 0 0 0
Experienced at least one drug-related TEAE 3 3 3
Experienced at least one SAE 0 2 2
At least one severe or life- threatening TEAE 1 1 1
At least one IRR (infusion related reaction) 1 1 1
Time Frame Baseline to EOS
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Replagal® (0.2 mg/kg, IV, EOW)
Hide Arm/Group Description Overall patients that participated in REP-082
All-Cause Mortality
Replagal® (0.2 mg/kg, IV, EOW)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Replagal® (0.2 mg/kg, IV, EOW)
Affected / at Risk (%) # Events
Total   2/17 (11.76%)    
Cardiac disorders   
Cardiac arrest  1  1/17 (5.88%)  1
Ventricular fibrillation  1  1/17 (5.88%)  1
Respiratory, thoracic and mediastinal disorders   
Pneumothorax  1  1/17 (5.88%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Replagal® (0.2 mg/kg, IV, EOW)
Affected / at Risk (%) # Events
Total   12/17 (70.59%)    
Cardiac disorders   
Bradycardia  1  1/17 (5.88%)  1
Eye disorders   
Visual impairment  1  1/17 (5.88%)  2
Gastrointestinal disorders   
Abdominal discomfort  1  1/17 (5.88%)  1
Abdominal pain  1  2/17 (11.76%)  4
Constipation  1  1/17 (5.88%)  1
Diarrhoea  1  3/17 (17.65%)  5
Nausea  1  2/17 (11.76%)  5
Vomiting  1  2/17 (11.76%)  2
General disorders   
Fatigue  1  3/17 (17.65%)  3
Oedema peripheral  1  2/17 (11.76%)  3
Pyrexia  1  1/17 (5.88%)  1
Infections and infestations   
Gastroenteritis viral  1  1/17 (5.88%)  1
Nasopharyngitis  1  1/17 (5.88%)  3
Upper respiratory tract infection  1  2/17 (11.76%)  3
Injury, poisoning and procedural complications   
Excoriation  1  1/17 (5.88%)  1
Joint sprain  1  1/17 (5.88%)  1
Procedural pain  1  1/17 (5.88%)  1
Investigations   
Blood potassium decreased  1  1/17 (5.88%)  1
Musculoskeletal and connective tissue disorders   
Back pain  1  2/17 (11.76%)  5
Muscular weakness  1  1/17 (5.88%)  1
Myalgia  1  1/17 (5.88%)  1
Sensation of heaviness  1  1/17 (5.88%)  1
Tendonitis  1  1/17 (5.88%)  1
Nervous system disorders   
Dizziness  1  2/17 (11.76%)  5
Headache  1  2/17 (11.76%)  4
Migraine  1  1/17 (5.88%)  1
Paraesthesia  1  2/17 (11.76%)  7
Psychiatric disorders   
Depression  1  1/17 (5.88%)  1
Stress  1  1/17 (5.88%)  1
Renal and urinary disorders   
Haematuria  1  1/17 (5.88%)  1
Reproductive system and breast disorders   
Gynaecomastia  1  1/17 (5.88%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  1/17 (5.88%)  1
Epistaxis  1  1/17 (5.88%)  2
Nasal congestion  1  2/17 (11.76%)  2
Oropharyngeal pain  1  1/17 (5.88%)  2
Sinus congestion  1  1/17 (5.88%)  1
Skin and subcutaneous tissue disorders   
Hyperhidrosis  1  1/17 (5.88%)  1
Pruritus  1  1/17 (5.88%)  1
Rash  1  1/17 (5.88%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Study Physician
Organization: Shire Development LLC
Phone: +1 866 842 5335
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01304277     History of Changes
Other Study ID Numbers: HGT-REP-082
First Submitted: February 15, 2011
First Posted: February 25, 2011
Results First Submitted: December 30, 2013
Results First Posted: April 25, 2014
Last Update Posted: April 25, 2014