A Safety and Efficacy Study of Fabrazyme® Replacement Therapy in Patients With Cardiac Fabry Disease

• ClinicalTrials.gov Identifier: NCT00140621
• Recruitment Status: Completed
• First Posted: September 1, 2005
• Results First Posted: April 15, 2015
• Last Update Posted: May 12, 2015
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Fabry Disease
• Intervention: Drug: Agalsidase beta
• Enrollment: 6

Participant Flow

Recruitment Details	The study was conducted at 7 centers between July 06, 2005 and August 6, 2012. One participant was treated at 2 study sites because the participant had to be transferred to another site during the study.
Pre-assignment Details

Arm/Group Title	Agalsidase Beta (Fabrazyme [Recombinant Form])
Arm/Group Description	Agalsidase beta 1 milligram per kilogram (mg/kg) intravenously once every 2 weeks up to 156 weeks.
Period Title: Overall Study
Started	6
Completed	6
Not Completed	0

Baseline Characteristics

Arm/Group Title		Agalsidase Beta
Arm/Group Description		Agalsidase beta 1 mg/kg intravenously once every 2 weeks up to 156 weeks.
Overall Number of Baseline Participants		6
Baseline Analysis Population Description		Efficacy evaluable population (EEP) included all registered participants except those who had serious deviations from protocol compliance requirements, did not receive study drug, had no data available at baseline or after study drug administration, and who were found to have no condition in cardiac Fabry disease.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	6 participants
		53.8 (5.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants
	Female	5 83.3%
	Male	1 16.7%
Weight; Mean (Standard Deviation); Unit of measure: Kilograms (kg)
	Number Analyzed	6 participants
		58.50 (9.24)
Height; Mean (Standard Deviation); Unit of measure: Centimeters (cm)
	Number Analyzed	6 participants
		156.63 (7.20)
Left Ventricular Hypertrophy; Measure Type: Number; Unit of measure: Participants	Number Analyzed	6 participants
No		0
Yes		6
Globotriaosylceramide (GL-3) Accumulation in the Myocardium; Measure Type: Number; Unit of measure: Participants	Number Analyzed	6 participants
No		0
Yes		1
Not Measured		5

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156
Description	Interventricular septum and left ventricular posterior wall thickness was assessed by echocardiogram.
Time Frame	Baseline to Week 156

Outcome Measure Data

Analysis Population Description

EEP.

Arm/Group Title	Agalsidase Beta
Arm/Group Description:	Agalsidase beta 1 mg/kg once every 2 weeks as an intravenous infusion up to 156 weeks.
Overall Number of Participants Analyzed	6
Least Squares Mean (95% Confidence Interval); Unit of Measure: percent change
Interventricular septum wall thickness	-3.31; (-19.67 to 16.39)
Left ventricular posterior wall thickness	-6.34; (-21.47 to 11.71)

2. Primary Outcome

Title	Change From Baseline in Interventricular Septum and Left Ventricular Posterior Wall Thickness at Week 156
Description	Interventricular septum and left ventricular posterior wall thickness was assessed by echocardiogram.
Time Frame	Baseline to Week 156

Outcome Measure Data

Analysis Population Description

EEP.

Arm/Group Title	Agalsidase Beta
Arm/Group Description:	Agalsidase beta 1 mg/kg once every 2 weeks as an intravenous infusion up to 156 weeks.
Overall Number of Participants Analyzed	6
Least Squares Mean (95% Confidence Interval); Unit of Measure: mm
Interventricular septum wall thickness	0.37; (-3.88 to 4.61)
Left ventricular posterior wall thickness	-0.33; (-3.31 to 2.64)

3. Primary Outcome

Title	Percent Change From Baseline in Left Ventricular Mass (LVM) at Week 156
Description	Left ventricular mass was assessed by echocardiogram.
Time Frame	Baseline to Week 156

Outcome Measure Data

Analysis Population Description

EEP.

Arm/Group Title	Agalsidase Beta
Arm/Group Description:	Agalsidase beta 1 mg/kg once every 2 weeks as an intravenous infusion up to 156 weeks.
Overall Number of Participants Analyzed	6
Least Squares Mean (95% Confidence Interval); Unit of Measure: percent change
	-4.14; (-24.35 to 21.47)

4. Primary Outcome

Title	Change From Baseline in LVM at Week 156
Description	Left ventricular mass was assessed by echocardiogram.
Time Frame	Baseline to Week 156

Outcome Measure Data

Analysis Population Description

EEP.

Arm/Group Title	Agalsidase Beta
Arm/Group Description:	Agalsidase beta 1 mg/kg once every 2 weeks as an intravenous infusion up to 156 weeks.
Overall Number of Participants Analyzed	6
Least Squares Mean (95% Confidence Interval); Unit of Measure: gm
	22.70; (-106.57 to 151.97)

5. Secondary Outcome

Title	Number of Participants in Overall Cardiac Function Assessment and Clinical Symptoms at Week 156: Change From Baseline in Cardiac Function Test
Description	Overall cardiac function assessment was assessed by tests (echocardiogram,cardiac catheterization (optional),electrocardiogram,B-type natriuretic peptide [BNP]), clinical symptoms (subjective symptoms) and the New York Heart Association (NYHA) cardiac functional classification.Overall assessment of cardiac function was assessed based on the evaluation items including interventricular septum thickness, left ventricular posterior wall thickness, left ventricular mass, clinical function tests and clinical symptoms. A subject was considered to be Improved: if Improved in 2 items or more, Unchanged: Improved in one item and unchanged in 2 items or unchanged in all 3 items, Aggravated: Aggravated in one item or more.
Time Frame	Baseline to Week 156

Outcome Measure Data

Analysis Population Description

EEP.

Arm/Group Title	Agalsidase Beta
Arm/Group Description:	Agalsidase beta 1 mg/kg once every 2 weeks as an intravenous infusion up to 156 weeks.
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: participants
Improved	5
Unchanged	0
Aggravated	1

6. Secondary Outcome

Title	Percent Change From Baseline in GL-3 Plasma Levels at Week 156
Description	[Not Specified]
Time Frame	Baseline to Week 156

Outcome Measure Data

Analysis Population Description

EEP.

Arm/Group Title	Agalsidase Beta
Arm/Group Description:	Agalsidase beta 1 mg/kg once every 2 weeks as an intravenous infusion up to 156 weeks.
Overall Number of Participants Analyzed	6
Least Squares Mean (95% Confidence Interval); Unit of Measure: percent change
	-18.91; (-42.35 to 14.07)

7. Secondary Outcome

Title	Change From Baseline in Short Form (36) Health Survey (SF-36) Scores at Week 156
Description	The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical component score (PCS) and mental component score (MCS). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).
Time Frame	Baseline to Week 156

Outcome Measure Data

Analysis Population Description

EEP.

Arm/Group Title	Agalsidase Beta
Arm/Group Description:	Agalsidase beta 1 mg/kg once every 2 weeks as an intravenous infusion up to 156 weeks.
Overall Number of Participants Analyzed	6
Mean (Standard Deviation); Unit of Measure: units on a scale
Physical Health: PCS	6.868 (15.238)
Mental Health: MCS	4.380 (7.425)

Adverse Events

Time Frame	All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 156) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (from the first study infusion up to Week 156).
Arm/Group Title	Agalsidase Beta
Arm/Group Description	Agalsidase beta 1 mg/kg once every 2 weeks as an intravenous infusion up to 156 weeks.
All-Cause Mortality
	Agalsidase Beta
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Agalsidase Beta
	Affected / at Risk (%)
Total	1/6 (16.67%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Large intestine carcinoma † 1	1/6 (16.67%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDra 15.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Agalsidase Beta
	Affected / at Risk (%)
Total	6/6 (100.00%)
Cardiac disorders
Palpitations † 1	4/6 (66.67%)
Atrial fibrillation † 1	1/6 (16.67%)
Atrioventricular block † 1	1/6 (16.67%)
Bradycardia † 1	1/6 (16.67%)
Bundle branch block right † 1	1/6 (16.67%)
Left ventricular hypertrophy † 1	1/6 (16.67%)
Supraventricular extrasystoles † 1	1/6 (16.67%)
Tachycardia † 1	1/6 (16.67%)
Ventricular hypertrophy † 1	1/6 (16.67%)
Gastrointestinal disorders
Abdominal pain upper † 1	1/6 (16.67%)
Colonic polyp † 1	1/6 (16.67%)
Dental caries † 1	1/6 (16.67%)
Diarrhoea † 1	1/6 (16.67%)
Gastritis erosive † 1	1/6 (16.67%)
Nausea † 1	1/6 (16.67%)
Oral pain † 1	1/6 (16.67%)
Stomatitis † 1	1/6 (16.67%)
Vomiting † 1	1/6 (16.67%)
General disorders
Oedema † 1	2/6 (33.33%)
Chest discomfort † 1	1/6 (16.67%)
Chest pain † 1	1/6 (16.67%)
Chills † 1	1/6 (16.67%)
Feeling hot † 1	1/6 (16.67%)
Injection site inflammation † 1	1/6 (16.67%)
Puncture site haemorrhage † 1	1/6 (16.67%)
Tenderness † 1	1/6 (16.67%)
Infections and infestations
Nasopharyngitis † 1	5/6 (83.33%)
Chronic sinusitis † 1	1/6 (16.67%)
Cystitis † 1	1/6 (16.67%)
Pharyngitis † 1	1/6 (16.67%)
Rhinitis † 1	1/6 (16.67%)
Investigations
Aspartate aminotransferase increased † 1	2/6 (33.33%)
Alanine aminotransferase increased † 1	1/6 (16.67%)
Blood pressure decreased † 1	1/6 (16.67%)
Blood urea increased † 1	1/6 (16.67%)
Body temperature decreased † 1	1/6 (16.67%)
Heart rate increased † 1	1/6 (16.67%)
Occult blood † 1	1/6 (16.67%)
Protein urine present † 1	1/6 (16.67%)
White blood cell count decreased † 1	1/6 (16.67%)
Metabolism and nutrition disorders
Dehydration † 1	1/6 (16.67%)
Hyperlipidaemia † 1	1/6 (16.67%)
Musculoskeletal and connective tissue disorders
Back pain † 1	3/6 (50.00%)
Pain in extremity † 1	2/6 (33.33%)
Arthralgia † 1	1/6 (16.67%)
Joint swelling † 1	1/6 (16.67%)
Musculoskeletal stiffness † 1	1/6 (16.67%)
Neck pain † 1	1/6 (16.67%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Large intestine carcinoma † 1	1/6 (16.67%)
Nervous system disorders
Headache † 1	2/6 (33.33%)
Dizziness † 1	1/6 (16.67%)
Intercostal neuralgia † 1	1/6 (16.67%)
Paraesthesia † 1	1/6 (16.67%)
Syncope † 1	1/6 (16.67%)
Psychiatric disorders
Anxiety disorder † 1	2/6 (33.33%)
Insomnia † 1	1/6 (16.67%)
Middle insomnia † 1	1/6 (16.67%)
Renal and urinary disorders
Dysuria † 1	1/6 (16.67%)
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic † 1	1/6 (16.67%)
Throat tightness † 1	1/6 (16.67%)
Skin and subcutaneous tissue disorders
Pruritus † 1	2/6 (33.33%)
Dermatitis contact † 1	1/6 (16.67%)
Eczema † 1	1/6 (16.67%)
Rash † 1	1/6 (16.67%)
Seborrhoeic dermatitis † 1	1/6 (16.67%)
Urticaria † 1	1/6 (16.67%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDra 15.0

Limitations and Caveats

[Not Specified]

More Information

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.

Prior to publishing results from this study in academic meetings, medical journals, etc., the investigator and subinvestigator of the post-manufacturing/marketing clinical study must obtain the approval from the sponsor of the post-manufacturing/marketing clinical study in writing.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Sanofi
• EMail: Contact-US@Sanofi.com

• Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
• ClinicalTrials.gov Identifier: NCT00140621
• Other Study ID Numbers: AGAL03204
• First Submitted: August 30, 2005
• First Posted: September 1, 2005
• Results First Submitted: April 1, 2015
• Results First Posted: April 15, 2015
• Last Update Posted: May 12, 2015