Trial Outcomes & Findings for Safety Study of Replagal® Therapy in Children With Fabry Disease (NCT NCT01363492)

NCT ID: NCT01363492

Last Updated: 2021-06-09

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

Baseline to week 55

Results posted on

2021-06-09

Participant Flow

Participant milestones

Participant milestones
Measure
Replagal® (0.2 mg/kg)
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Overall Study
STARTED
14
Overall Study
COMPLETED
14
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety Study of Replagal® Therapy in Children With Fabry Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Replagal (0.2 mg/kg)
n=14 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes EOW
Age, Continuous
12.16 Years
STANDARD_DEVIATION 2.992 • n=5 Participants
Age, Customized
<=18 years
14 Participants
n=5 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
Sex: Female, Male
Male
5 Participants
n=5 Participants
Region of Enrollment
UNITED STATES
14 Participants
n=5 Participants
Heart rate variability parameter SDNN
103.46 msec
STANDARD_DEVIATION 32.928 • n=5 Participants
Heart rate variability parameter rMSSD
75.92 msec
STANDARD_DEVIATION 45.747 • n=5 Participants
Heart rate variability parameter pNN50
32.79 msec
STANDARD_DEVIATION 19.997 • n=5 Participants
Left Ventricular Mass Index (LVMI)
35.37 (g/m^2.7)
STANDARD_DEVIATION 10.129 • n=5 Participants
Midwall Fractional Shortening (MFS)
18.63 (%)
STANDARD_DEVIATION 2.891 • n=5 Participants
Plasma Gb3
14.79 (nmol/mL)
STANDARD_DEVIATION 12.228 • n=5 Participants
Urine Gb3
1775.08 (nmol/g creatinine)
STANDARD_DEVIATION 3691.087 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to week 55

Outcome measures

Outcome measures
Measure
Replagal (0.2 mg/kg)
n=14 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Number of Serious Adverse Event (SAE)
0 events

PRIMARY outcome

Timeframe: Baseline to week 55

Outcome measures

Outcome measures
Measure
Replagal (0.2 mg/kg)
n=14 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Number of Treatment Emergent Adverse Event (TEAE)
166 events

PRIMARY outcome

Timeframe: Baseline to Week 55

Reflects development of Anti-Agalsidase antibodies post baseline

Outcome measures

Outcome measures
Measure
Replagal (0.2 mg/kg)
n=14 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Development of IgG Anti-Agalsidase Alfa Antibody
1 participants

PRIMARY outcome

Timeframe: Baseline to week 55

Outcome measures

Outcome measures
Measure
Replagal (0.2 mg/kg)
n=13 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Change From Baseline in Heart Rate Variability Parameter SDNN
10.46 msec
Standard Deviation 24.223

PRIMARY outcome

Timeframe: Baseline to week 55

Outcome measures

Outcome measures
Measure
Replagal (0.2 mg/kg)
n=13 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Change From Baseline in Heart Rate Variability Parameter rMSSD
1.46 msec
Standard Deviation 53.502

PRIMARY outcome

Timeframe: Baseline to week 55

Outcome measures

Outcome measures
Measure
Replagal (0.2 mg/kg)
n=13 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Change From Baseline in Heart Rate Variability Parameter pNN50
-4.13 msec
Standard Deviation 20.166

SECONDARY outcome

Timeframe: Baseline to week 55

Outcome measures

Outcome measures
Measure
Replagal (0.2 mg/kg)
n=14 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Change From Baseline in LVMI
0.16 (g/m^2.7)
Standard Deviation 6.059

SECONDARY outcome

Timeframe: Baseline to week 55

Outcome measures

Outcome measures
Measure
Replagal (0.2 mg/kg)
n=14 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Change From Baseline in MFS
-0.62 (%)
Standard Deviation 3.596

SECONDARY outcome

Timeframe: Baseline to week 55

Outcome measures

Outcome measures
Measure
Replagal (0.2 mg/kg)
n=14 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Change From Baseline in Plasma Gb3
-5.71 (nmol/mL)
Standard Deviation 8.799

SECONDARY outcome

Timeframe: Baseline to week 55

Outcome measures

Outcome measures
Measure
Replagal (0.2 mg/kg)
n=12 Participants
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes every other week (EOW)
Change From Baseline in Urine Gb3
-1403.25 (nmol/g creatinine)
Standard Deviation 3636.711

Adverse Events

Replagal® (0.2 mg/kg)

Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Replagal® (0.2 mg/kg)
n=14 participants at risk
0.2 mg/kg Replagal (agalsidase alfa) administered over 40 minutes EOW
Blood and lymphatic system disorders
Anaemia
7.1%
1/14 • Number of events 1 • Baseline to week 55
Blood and lymphatic system disorders
Iron deficiency anaemia
7.1%
1/14 • Number of events 1 • Baseline to week 55
Cardiac disorders
Sinus bradycardia
7.1%
1/14 • Number of events 1 • Baseline to week 55
Ear and labyrinth disorders
Ear pain
14.3%
2/14 • Number of events 2 • Baseline to week 55
Eye disorders
Hordeolum
7.1%
1/14 • Number of events 1 • Baseline to week 55
Eye disorders
Retinal vascular disorder
7.1%
1/14 • Number of events 1 • Baseline to week 55
Gastrointestinal disorders
Abdominal pain
7.1%
1/14 • Number of events 2 • Baseline to week 55
Gastrointestinal disorders
Abdominal pain upper
14.3%
2/14 • Number of events 2 • Baseline to week 55
Gastrointestinal disorders
Diarrhoea
28.6%
4/14 • Number of events 5 • Baseline to week 55
Gastrointestinal disorders
Dyspepsia
7.1%
1/14 • Number of events 1 • Baseline to week 55
Gastrointestinal disorders
Mouth ulceration
7.1%
1/14 • Number of events 1 • Baseline to week 55
Gastrointestinal disorders
Nausea
28.6%
4/14 • Number of events 12 • Baseline to week 55
Gastrointestinal disorders
Tooth malformation
7.1%
1/14 • Number of events 1 • Baseline to week 55
Gastrointestinal disorders
Vomiting
28.6%
4/14 • Number of events 12 • Baseline to week 55
General disorders
Chest discomfort
14.3%
2/14 • Number of events 2 • Baseline to week 55
General disorders
Chills
14.3%
2/14 • Number of events 2 • Baseline to week 55
General disorders
Fatigue
7.1%
1/14 • Number of events 1 • Baseline to week 55
General disorders
Feeling cold
7.1%
1/14 • Number of events 2 • Baseline to week 55
General disorders
Malaise
7.1%
1/14 • Number of events 1 • Baseline to week 55
General disorders
Non-cardiac chest pain
7.1%
1/14 • Number of events 1 • Baseline to week 55
General disorders
Pain
14.3%
2/14 • Number of events 2 • Baseline to week 55
General disorders
Pyrexia
42.9%
6/14 • Number of events 8 • Baseline to week 55
Immune system disorders
Seasonal allergy
7.1%
1/14 • Number of events 1 • Baseline to week 55
Infections and infestations
Alveolar osteitis
7.1%
1/14 • Number of events 1 • Baseline to week 55
Infections and infestations
Gastroenteritis
14.3%
2/14 • Number of events 4 • Baseline to week 55
Infections and infestations
Gastroenteritis viral
14.3%
2/14 • Number of events 2 • Baseline to week 55
Infections and infestations
Infectious mononucleosis
7.1%
1/14 • Number of events 1 • Baseline to week 55
Infections and infestations
Nasopharyngitis
21.4%
3/14 • Number of events 3 • Baseline to week 55
Infections and infestations
Otitis media
7.1%
1/14 • Number of events 1 • Baseline to week 55
Infections and infestations
Pharyngitis streptococcal
14.3%
2/14 • Number of events 2 • Baseline to week 55
Infections and infestations
Rhinitis
14.3%
2/14 • Number of events 2 • Baseline to week 55
Infections and infestations
Sinusitis
21.4%
3/14 • Number of events 4 • Baseline to week 55
Infections and infestations
Upper respiratory tract infection
28.6%
4/14 • Number of events 5 • Baseline to week 55
Injury, poisoning and procedural complications
Avulsion fracture
7.1%
1/14 • Number of events 1 • Baseline to week 55
Injury, poisoning and procedural complications
Contusion
7.1%
1/14 • Number of events 1 • Baseline to week 55
Injury, poisoning and procedural complications
Facial bones fracture
7.1%
1/14 • Number of events 1 • Baseline to week 55
Injury, poisoning and procedural complications
Scratch
7.1%
1/14 • Number of events 1 • Baseline to week 55
Injury, poisoning and procedural complications
Tooth fracture
7.1%
1/14 • Number of events 1 • Baseline to week 55
Investigations
Body temperature increased
7.1%
1/14 • Number of events 1 • Baseline to week 55
Investigations
Heart rate increased
7.1%
1/14 • Number of events 1 • Baseline to week 55
Investigations
Liver palpable subcostal
7.1%
1/14 • Number of events 1 • Baseline to week 55
Metabolism and nutrition disorders
Decreased appetite
7.1%
1/14 • Number of events 1 • Baseline to week 55
Metabolism and nutrition disorders
Hyperlipidaemia
7.1%
1/14 • Number of events 1 • Baseline to week 55
Musculoskeletal and connective tissue disorders
Arthralgia
14.3%
2/14 • Number of events 2 • Baseline to week 55
Musculoskeletal and connective tissue disorders
Muscular weakness
7.1%
1/14 • Number of events 1 • Baseline to week 55
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
7.1%
1/14 • Number of events 1 • Baseline to week 55
Musculoskeletal and connective tissue disorders
Pain in extremity
28.6%
4/14 • Number of events 7 • Baseline to week 55
Nervous system disorders
Dizziness
14.3%
2/14 • Number of events 2 • Baseline to week 55
Nervous system disorders
Headache
28.6%
4/14 • Number of events 7 • Baseline to week 55
Nervous system disorders
Paraesthesia
14.3%
2/14 • Number of events 2 • Baseline to week 55
Psychiatric disorders
Restlessness
7.1%
1/14 • Number of events 1 • Baseline to week 55
Renal and urinary disorders
Proteinuria
14.3%
2/14 • Number of events 2 • Baseline to week 55
Respiratory, thoracic and mediastinal disorders
Asthma
7.1%
1/14 • Number of events 1 • Baseline to week 55
Respiratory, thoracic and mediastinal disorders
Cough
28.6%
4/14 • Number of events 8 • Baseline to week 55
Respiratory, thoracic and mediastinal disorders
Dyspnoea
21.4%
3/14 • Number of events 11 • Baseline to week 55
Respiratory, thoracic and mediastinal disorders
Nasal congestion
7.1%
1/14 • Number of events 1 • Baseline to week 55
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
7.1%
1/14 • Number of events 1 • Baseline to week 55
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema
14.3%
2/14 • Number of events 2 • Baseline to week 55
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
7.1%
1/14 • Number of events 1 • Baseline to week 55
Respiratory, thoracic and mediastinal disorders
Throat irritation
14.3%
2/14 • Number of events 3 • Baseline to week 55
Respiratory, thoracic and mediastinal disorders
Throat tightness
7.1%
1/14 • Number of events 1 • Baseline to week 55
Skin and subcutaneous tissue disorders
Acne
14.3%
2/14 • Number of events 2 • Baseline to week 55
Skin and subcutaneous tissue disorders
Angioedema
7.1%
1/14 • Number of events 1 • Baseline to week 55
Skin and subcutaneous tissue disorders
Erythema
7.1%
1/14 • Number of events 1 • Baseline to week 55
Skin and subcutaneous tissue disorders
Petechiae
7.1%
1/14 • Number of events 1 • Baseline to week 55
Skin and subcutaneous tissue disorders
Pityriasis rosea
7.1%
1/14 • Number of events 1 • Baseline to week 55
Skin and subcutaneous tissue disorders
Pruritus
7.1%
1/14 • Number of events 1 • Baseline to week 55
Skin and subcutaneous tissue disorders
Rash
7.1%
1/14 • Number of events 1 • Baseline to week 55
Skin and subcutaneous tissue disorders
Urticaria
7.1%
1/14 • Number of events 1 • Baseline to week 55
Vascular disorders
Flushing
7.1%
1/14 • Number of events 4 • Baseline to week 55
Vascular disorders
Hypotension
7.1%
1/14 • Number of events 1 • Baseline to week 55

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

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