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Safety, Pharmacokinetics, and Pharmacodynamics/Efficacy of SBC-103 in Mucopolysaccharidosis III, Type B (MPS IIIB)

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ClinicalTrials.gov Identifier: NCT02324049
Recruitment Status : Completed
First Posted : December 24, 2014
Results First Posted : July 12, 2018
Last Update Posted : August 21, 2018
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Mucopolysaccharidosis IIIB
Intervention Drug: SBC-103
Enrollment 11
Recruitment Details Diagnosis of mucopolysaccharidosis III, type B (MPS IIIB), determined by either documented deficiency in Alpha-N-acetylglucosaminidase (NAGLU) enzyme activity ≤10% of the mean value in normal individuals at Screening OR documented functionally-relevant mutations in both alleles of the NAGLU gene based on historical or Screening laboratory results.
Pre-assignment Details  
Arm/Group Title SBC-103
Hide Arm/Group Description

Part A (Initial therapy): Participants received SBC-103, 0.3, 1.0, or 3.0 milligrams (mg) per kilogram (kg) every other week (QOW) for 24 weeks, followed by a ≥ 4-week treatment break. Participants enrolled in the lowest dosage first.

Part B: Participants were escalated to the next highest dose that was considered safe (1.0 or 3.0 mg/kg QOW) for ≥ 8 weeks. Participants who received doses of 0.3 mg/kg in Part A were considered for a second dose escalation to 3.0 mg/kg at any time during Part B provided that they tolerated at least 2 doses of 1.0 mg/kg in Part B. Participants who received and tolerated at least 4 doses of SBC-103 QOW at 3.0 mg/kg were considered for participation in Part C.

Part C: Participants received SBC-103 5.0 or 10.0 mg/kg administered intravenous (IV) QOW. Dosing in Part C began at the 5.0 mg/kg dose level. The decision to begin dosing the first participant at 10.0 mg/kg was based on the review of safety data at 5.0 mg/kg.

Period Title: Part A
Started 11
Safety Analysis Set 11 [1]
Completed 11
Not Completed 0
[1]
Participants with informed consent, confirmed MPS IIIB diagnosis, and received any amount of SBC-103
Period Title: Part B
Started 11
Safety Analysis Set 11
Completed 11
Not Completed 0
Period Title: Part C
Started 11
Safety Analysis Set 11
Completed 0
Not Completed 11
Reason Not Completed
Study terminated             11
Arm/Group Title SBC-103
Hide Arm/Group Description

Part A (Initial therapy): Participants received SBC-103, 0.3, 1.0, or 3.0 mg/kg QOW for 24 weeks, followed by a ≥ 4-week treatment break. Participants enrolled in the lowest dosage first.

Part B: Participants were escalated to the next highest dose that was considered safe (1.0 or 3.0 mg/kg QOW) for ≥ 8 weeks. Participants who received doses of 0.3 mg/kg in Part A were considered for a second dose escalation to 3.0 mg/kg at any time during Part B provided that they tolerated at least 2 doses of 1.0 mg/kg in Part B. Participants who received and tolerated at least 4 doses of SBC-103 QOW at 3.0 mg/kg were considered for participation in Part C.

Part C: Participants received SBC-103 5.0 or 10.0 mg/kg administered IV QOW. Dosing in Part C began at the 5.0 mg/kg dose level. The decision to begin dosing the first participant at 10.0 mg/kg was based on the review of safety data at 5.0 mg/kg.

Overall Number of Baseline Participants 11
Hide Baseline Analysis Population Description
Safety Population: all participants for whom informed consent had been obtained, who had a confirmed diagnosis of MPS IIIB, and who had received any amount of SBC-103.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
<=18 years
11
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Female
4
  36.4%
Male
7
  63.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Hispanic or Latino
1
   9.1%
Not Hispanic or Latino
10
  90.9%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   9.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
9
  81.8%
More than one race
0
   0.0%
Unknown or Not Reported
1
   9.1%
Overall Age at Diagnosis   [1] 
Median (Full Range)
Unit of measure:  Months
5.0 mg/kg Number Analyzed 5 participants
48.0
(18 to 57)
10.0 mg/kg Number Analyzed 6 participants
25.0
(12 to 77)
Overall Number Analyzed 11 participants
37.0
(12 to 77)
[1]
Measure Analysis Population Description: There were 5 participants in the 5.0 mg/kg group and 6 participants in the 10.0 mg/kg group.
1.Primary Outcome
Title Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Hide Description TEAEs were defined as any adverse event (AE) that occurred after administration of the first dose of study drug on Day 1 (Part A). A severe AE was defined as an AE that was incapacitating and required medical intervention. TEAEs were summarized cumulatively over the entire study and separately for Part C, data for all severe TEAEs throughout the entire study is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time Frame Baseline to Week 142
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population: all participants for whom informed consent had been obtained, who had a confirmed diagnosis of MPS IIIB, and who had received any amount of SBC-103.
Arm/Group Title SBC-103
Hide Arm/Group Description:

Part A (Initial therapy): Participants received SBC-103, 0.3, 1.0, or 3.0 mg/kg QOW for 24 weeks, followed by a ≥ 4-week treatment break. Participants enrolled in the lowest dosage first.

Part B: Participants were escalated to the next highest dose that was considered safe (1.0 or 3.0 mg/kg QOW) for ≥ 8 weeks. Participants who received doses of 0.3 mg/kg in Part A were considered for a second dose escalation to 3.0 mg/kg at any time during Part B provided that they tolerated at least 2 doses of 1.0 mg/kg in Part B. Participants who received and tolerated at least 4 doses of SBC-103 QOW at 3.0 mg/kg were considered for participation in Part C.

Part C: Participants received SBC-103 5.0 or 10.0 mg/kg administered IV QOW. Dosing in Part C began at the 5.0 mg/kg dose level. The decision to begin dosing the first participant at 10.0 mg/kg was based on the review of safety data at 5.0 mg/kg.

Overall Number of Participants Analyzed 11
Measure Type: Count of Participants
Unit of Measure: Participants
5.0 mg/kg 1
10.0 mg/kg 0
Overall 1
Time Frame Day 1 postdose up to Week 142
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title SBC-103
Hide Arm/Group Description

Part A (Initial therapy): Participants received SBC-103, 0.3, 1.0, or 3.0 mg/kg QOW for 24 weeks, followed by a ≥ 4-week treatment break. Participants enrolled in the lowest dosage first.

Part B: Participants were escalated to the next highest dose that was considered safe (1.0 or 3.0 mg/kg QOW) for ≥ 8 weeks. Participants who received doses of 0.3 mg/kg in Part A were considered for a second dose escalation to 3.0 mg/kg at any time during Part B provided that they tolerated at least 2 doses of 1.0 mg/kg in Part B. Participants who received and tolerated at least 4 doses of SBC-103 QOW at 3.0 mg/kg were considered for participation in Part C.

Part C: Participants received SBC-103 5.0 or 10.0 mg/kg administered IV QOW. Dosing in Part C began at the 5.0 mg/kg dose level. The decision to begin dosing the first participant at 10.0 mg/kg was based on the review of safety data at 5.0 mg/kg.

All-Cause Mortality
SBC-103
Affected / at Risk (%)
Total   0/11 (0.00%) 
Hide Serious Adverse Events
SBC-103
Affected / at Risk (%)
Total   3/11 (27.27%) 
Cardiac disorders   
Cyanosis  1  1/11 (9.09%) 
General disorders   
Pyrexia  1  1/11 (9.09%) 
Infections and infestations   
Bacteraemia  1  1/11 (9.09%) 
Pneumonia  1  1/11 (9.09%) 
Staphylococcal bacteraemia  1  1/11 (9.09%) 
Investigations   
Blood pressure increased  1  1/11 (9.09%) 
Respiratory, thoracic and mediastinal disorders   
Hypoxia  1  1/11 (9.09%) 
Skin and subcutaneous tissue disorders   
Urticaria  1  1/11 (9.09%) 
Swelling face  1  1/11 (9.09%) 
Vascular disorders   
Flushing  1  1/11 (9.09%) 
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
SBC-103
Affected / at Risk (%)
Total   11/11 (100.00%) 
Blood and lymphatic system disorders   
Anaemia  1  2/11 (18.18%) 
Lymphadenopathy  1  2/11 (18.18%) 
Cardiac disorders   
Left ventricular hypertrophy  1  1/11 (9.09%) 
Sinus bradycardia  1  1/11 (9.09%) 
Tachycardia  1  1/11 (9.09%) 
Congenital, familial and genetic disorders   
Dysmorphism  1  1/11 (9.09%) 
Ear and labyrinth disorders   
Deafness  1  4/11 (36.36%) 
Ear pain  1  2/11 (18.18%) 
Deafness bilateral  1  1/11 (9.09%) 
Hypoacusis  1  1/11 (9.09%) 
Middle ear effusion  1  1/11 (9.09%) 
Endocrine disorders   
Precocious puberty  1  1/11 (9.09%) 
Eye disorders   
Mydriasis  1  1/11 (9.09%) 
Eye swelling  1  1/11 (9.09%) 
Ocular hyperaemia  1  1/11 (9.09%) 
Gastrointestinal disorders   
Vomiting  1  7/11 (63.64%) 
Diarrhoea  1  6/11 (54.55%) 
Salivary hypersecretion  1  2/11 (18.18%) 
Constipation  1  1/11 (9.09%) 
Breath odour  1  1/11 (9.09%) 
Eructation  1  1/11 (9.09%) 
Lip swelling  1  1/11 (9.09%) 
Nausea  1  1/11 (9.09%) 
Pancreatic enlargement  1  1/11 (9.09%) 
Swollen tongue  1  1/11 (9.09%) 
General disorders   
Pyrexia  1  9/11 (81.82%) 
Catheter site erythema  1  2/11 (18.18%) 
Catheter site rash  1  1/11 (9.09%) 
Catheter site swelling  1  1/11 (9.09%) 
Influenza like illness  1  1/11 (9.09%) 
Local swelling  1  1/11 (9.09%) 
Pain  1  1/11 (9.09%) 
Infections and infestations   
Nasopharyngitis  1  5/11 (45.45%) 
Upper respiratory tract infection  1  4/11 (36.36%) 
Lower respiratory tract infection  1  2/11 (18.18%) 
Rhinitis  1  2/11 (18.18%) 
Gastroenteritis viral  1  2/11 (18.18%) 
Ear infection  1  1/11 (9.09%) 
Fungal skin infection  1  1/11 (9.09%) 
Hordeolum  1  1/11 (9.09%) 
Pharyngitis streptococcal  1  1/11 (9.09%) 
Candida nappy rash  1  1/11 (9.09%) 
Conjunctivitis  1  1/11 (9.09%) 
Eye infection  1  1/11 (9.09%) 
Eye infection bacterial  1  1/11 (9.09%) 
Folliculitis  1  1/11 (9.09%) 
Fungal infection  1  1/11 (9.09%) 
Influenza  1  1/11 (9.09%) 
Localised infection  1  1/11 (9.09%) 
Oral candidiasis  1  1/11 (9.09%) 
Oral herpes  1  1/11 (9.09%) 
Otitis externa  1  1/11 (9.09%) 
Otitis media  1  1/11 (9.09%) 
Paronychia  1  1/11 (9.09%) 
Respiratory tract infection viral  1  1/11 (9.09%) 
Rotavirus infection  1  1/11 (9.09%) 
Tonsillitis  1  1/11 (9.09%) 
Viral infection  1  1/11 (9.09%) 
Injury, poisoning and procedural complications   
Head injury  1  2/11 (18.18%) 
Fall  1  2/11 (18.18%) 
Infusion related reaction  1  1/11 (9.09%) 
Anaesthetic complication neurological  1  1/11 (9.09%) 
Contusion  1  1/11 (9.09%) 
Eye contusion  1  1/11 (9.09%) 
Eyelid injury  1  1/11 (9.09%) 
Foreign body  1  1/11 (9.09%) 
Lip injury  1  1/11 (9.09%) 
Mouth injury  1  1/11 (9.09%) 
Periorbital haemorrhage  1  1/11 (9.09%) 
Investigations   
Cardiac murmur  1  2/11 (18.18%) 
Body temperature increased  1  1/11 (9.09%) 
CSF protein increased  1  1/11 (9.09%) 
Electrocardiogram Q wave abnormal  1  1/11 (9.09%) 
Liver palpable  1  1/11 (9.09%) 
Mean platelet volume increased  1  1/11 (9.09%) 
Oxygen saturation decreased  1  1/11 (9.09%) 
Serum ferritin decreased  1  1/11 (9.09%) 
Metabolism and nutrition disorders   
Decreased appetite  1  1/11 (9.09%) 
Iron deficiency  1  1/11 (9.09%) 
Musculoskeletal and connective tissue disorders   
Coccydynia  1  1/11 (9.09%) 
Muscle mass  1  1/11 (9.09%) 
Musculoskeletal pain  1  1/11 (9.09%) 
Scoliosis  1  1/11 (9.09%) 
Nervous system disorders   
Headache  1  1/11 (9.09%) 
Hyperreflexia  1  1/11 (9.09%) 
Hypertonia  1  1/11 (9.09%) 
Lethargy  1  1/11 (9.09%) 
Psychomotor hyperactivity  1  1/11 (9.09%) 
Seizure  1  1/11 (9.09%) 
Speech disorder  1  1/11 (9.09%) 
Syncope  1  1/11 (9.09%) 
Product Issues   
Device occlusion  1  1/11 (9.09%) 
Psychiatric disorders   
Hypervigilance  1  2/11 (18.18%) 
Insomnia  1  2/11 (18.18%) 
Aggression  1  1/11 (9.09%) 
Agitation  1  1/11 (9.09%) 
Anxiety  1  1/11 (9.09%) 
Renal and urinary disorders   
Proteinuria  1  2/11 (18.18%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  5/11 (45.45%) 
Rhinorrhoea  1  3/11 (27.27%) 
Nasal congestion  1  3/11 (27.27%) 
Wheezing  1  1/11 (9.09%) 
Nasal obstruction  1  1/11 (9.09%) 
Asthma  1  1/11 (9.09%) 
Bronchial secretion retention  1  1/11 (9.09%) 
Oropharyngeal pain  1  1/11 (9.09%) 
Skin and subcutaneous tissue disorders   
Rash  1  4/11 (36.36%) 
Dermatitis diaper  1  4/11 (36.36%) 
Erythema  1  2/11 (18.18%) 
Rash erythematous  1  2/11 (18.18%) 
Dermatitis allergic  1  1/11 (9.09%) 
Dermatitis contact  1  1/11 (9.09%) 
Dry skin  1  1/11 (9.09%) 
Eczema  1  1/11 (9.09%) 
Miliaria  1  1/11 (9.09%) 
Papule  1  1/11 (9.09%) 
Seborrhoeic dermatitis  1  1/11 (9.09%) 
Skin discolouration  1  1/11 (9.09%) 
Skin plaque  1  1/11 (9.09%) 
Swelling face  1  1/11 (9.09%) 
Vascular disorders   
Flushing  1  2/11 (18.18%) 
Hyperaemia  1  2/11 (18.18%) 
Hypertension  1  2/11 (18.18%) 
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Alexion Pharmaceuticals, Inc.
Organization: Alexion Pharmaceuticals, Inc.
Phone: 475-230-2596
EMail: clinicaltrials@alexion.com
Layout table for additonal information
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02324049    
Other Study ID Numbers: NGLU-CL02
First Submitted: December 15, 2014
First Posted: December 24, 2014
Results First Submitted: June 12, 2018
Results First Posted: July 12, 2018
Last Update Posted: August 21, 2018