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Multicenter Study of HGT-1110 Administered Intrathecally in Children With Metachromatic Leukodystrophy (MLD) (IDEAMLD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01510028
Recruitment Status : Completed
First Posted : January 13, 2012
Results First Posted : October 15, 2018
Last Update Posted : June 18, 2019
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metachromatic Leukodystrophy (MLD)
Intervention Biological: Recombinant human arylsulfatase A
Enrollment 24
Recruitment Details The study was conducted at 5 main sites for cohorts 1 to 3 in Brazil, Denmark, Germany, France, and Australia and 3 main sites for cohort 4 in Denmark, France, and Germany between 02 February 2012 (first participant first visit) and 20 January 2017 (last participant last visit).
Pre-assignment Details A total of 34 participants were screened and 24 participants were enrolled in the study. Out of which 23 participants completed the study.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description Participants received 10 milligram (mg) dose of SHP611 (HGT-1110, recombinant human arylsulfatase A [rhASA]) every other week (EOW) by intrathecal drug delivery device (IDDD) for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A. Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A. Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A. Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Period Title: Overall Study
Started 6 6 6 6
Completed 5 6 6 6
Not Completed 1 0 0 0
Reason Not Completed
Lack of Efficacy             1             0             0             0
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B) Total
Hide Arm/Group Description Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A. Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A. Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A. Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B. Total of all reporting groups
Overall Number of Baseline Participants 6 6 6 6 24
Hide Baseline Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 6 participants 6 participants 6 participants 6 participants 24 participants
31.5  (11.50) 47.3  (20.23) 52.2  (31.17) 48.5  (24.22) 44.9  (22.85)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 24 participants
Female
3
  50.0%
3
  50.0%
1
  16.7%
2
  33.3%
9
  37.5%
Male
3
  50.0%
3
  50.0%
5
  83.3%
4
  66.7%
15
  62.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 6 participants 6 participants 24 participants
Race: White
5
  83.3%
4
  66.7%
2
  33.3%
4
  66.7%
15
  62.5%
Race: Asian
0
   0.0%
0
   0.0%
4
  66.7%
0
   0.0%
4
  16.7%
Race: Other
1
  16.7%
2
  33.3%
0
   0.0%
2
  33.3%
5
  20.8%
Ethnicity: Not Hispanic or Latino
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
24
 100.0%
1.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Type and Severity
Hide Description An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. Drug-related and device-related types of TEAEs were analyzed and reported. The severity of AEs was assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 grading scale. Severity of all AEs or SAEs was recorded as grade 1, 2, 3, 4, or 5 corresponding, respectively, to a severity of mild, moderate, severe, life-threatening, or fatal. Here SDI refers to surgical device implantation.
Time Frame From start of study treatment up to Week 42
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
TEAE
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
SHP611-related TEAE
3
  50.0%
4
  66.7%
4
  66.7%
2
  33.3%
SDI-related TEAE
5
  83.3%
3
  50.0%
4
  66.7%
4
  66.7%
IDDD-related TEAE
3
  50.0%
3
  50.0%
4
  66.7%
0
   0.0%
SOPH-A-PORT IDDD-related TEAE
0
   0.0%
0
   0.0%
4
  66.7%
0
   0.0%
IT administration process related TEAE
4
  66.7%
3
  50.0%
1
  16.7%
1
  16.7%
Severe TEAE
2
  33.3%
3
  50.0%
1
  16.7%
1
  16.7%
Serious TEAE
5
  83.3%
4
  66.7%
3
  50.0%
2
  33.3%
2.Primary Outcome
Title Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Hide Description Clinical laboratory test included serum chemistry, hematology and urinalysis. Clinical laboratory abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.
Time Frame From start of study treatment up to Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Gamma-glutamyltransferase (GGT) increased
2
  33.3%
1
  16.7%
1
  16.7%
0
   0.0%
Alanine aminotransferase (ALT) increased
1
  16.7%
1
  16.7%
0
   0.0%
1
  16.7%
Aspartate aminotransferase (AST) increased
0
   0.0%
1
  16.7%
1
  16.7%
0
   0.0%
Blood iron decreased
0
   0.0%
1
  16.7%
1
  16.7%
0
   0.0%
Amylase increased
0
   0.0%
1
  16.7%
1
  16.7%
0
   0.0%
Blood alkaline phosphatase increased
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
Blood creatine phosphokinase increased
0
   0.0%
0
   0.0%
0
   0.0%
3
  50.0%
Hepatic enzymes increased
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
Eosinophil count increased
0
   0.0%
1
  16.7%
1
  16.7%
0
   0.0%
Eosinophilia
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
Mean cell volume decreased
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
Neutrophil count increased
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
White blood cell count increased
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
Lymphopenia
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
Leukocytosis
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
Proteinuria
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
3.Primary Outcome
Title Number of Participants With Vital Sign Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Hide Description Vital sign assessments included blood pressure, heart rate, respiratory rate and body temperature. Vital sign abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date. Vital sign abnormalities included pyrexia which was considered as TEAE and was reported.
Time Frame From start of study treatment up to Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
5
  83.3%
3
  50.0%
5
  83.3%
5
  83.3%
4.Primary Outcome
Title Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Hide Description 12-lead ECG was recorded and measured with the participant in rested supine position for at least 10 minutes. ECG abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.
Time Frame From start of study treatment up to Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5.Primary Outcome
Title Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Treatment Emergent Adverse Events (TEAE)
Hide Description Complete physical examination included evaluation of the port and catheter track. Height or length and weight were recorded and used to calculate growth. Body weight and height measurements were used to calculate the body mass index (BMI). Head circumference was measured in uniform manner for all participants. Clinical significance was defined as any variation in physical findings that had medical relevance resulting in an alteration in medical care. Clinically significant abnormalities related to physical examination were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.
Time Frame From start of study treatment up to Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
6.Primary Outcome
Title Number of Participants With Cerebrospinal Fluid (CSF) Chemistry Abnormalities Reported as Treatment Emergent Adverse Events (TEAEs)
Hide Description CSF chemistry assessments (including cell counts, glucose and protein) was measured. CSF chemistry abnormalities were recorded and reported as TEAE. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as all AEs that occurred at or after the first dose of the investigational product or device implant surgery (whichever occurred earlier) and through the last follow-up date.
Time Frame From start of study treatment up to Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
CSF Protein Increased
0
   0.0%
0
   0.0%
1
  16.7%
1
  16.7%
CSF Albumin Increased
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
7.Primary Outcome
Title Number of Participants With Positive Anti-SHP611 Antibodies in Cerebrospinal Fluid (CSF) and or Serum
Hide Description Number of participants with positive anti-SHP611 antibody results in serum and in CSF were reported. A participant was considered positive if they had at least 1 positive result during the study.
Time Frame Baseline up to Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Serum anti-SHP611 antibody (Ab) positive
4
  66.7%
3
  50.0%
1
  16.7%
2
  33.3%
Serum neutralizing anti-SHP611 antibody positive
3
  50.0%
2
  33.3%
1
  16.7%
1
  16.7%
CSF anti-SHP611 antibody positive
3
  50.0%
1
  16.7%
0
   0.0%
2
  33.3%
CSF neutralizing anti-SHP611 antibody positive
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Serum or CSF anti-SHP611 antibody positive
4
  66.7%
3
  50.0%
1
  16.7%
2
  33.3%
Serum and CSF anti-SHP611 antibody positive
3
  50.0%
1
  16.7%
0
   0.0%
2
  33.3%
Serum or CSF neutralizing anti-SHP611 Ab positive
3
  50.0%
2
  33.3%
1
  16.7%
1
  16.7%
Serum and CSF neutralizing anti-SHP611 Ab positive
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
8.Secondary Outcome
Title Change From Baseline in Motor Function Using Gross Motor Function Measure 88 (GMFM-88) Total Score at Week 40
Hide Description The GMFM-88 was used to measure motor function. The GMFM-88 item scores were used to calculate domain-specific percent score for each of the 5 GMFM-88 dimensions (lying and rolling; sitting; crawling and kneeling; standing; walking, running, and jumping), and a total GMFM-88 (percent) score was calculated based on each dimension score. Each of the 88 items was rated on a 4-point scale: 0=does not initiate; 1=initiates; 2=partially completes; and 3=completes. The GMFM-88 total scores ranged from 0% (no mobility) to a score of 100%, that is (i.e,) the score that can be obtained by an average 5-year-old or older child with normal motor abilities.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Least Squares Mean (Standard Error)
Unit of Measure: Score on a Scale
-31.9  (8.76) -29.0  (8.58) -19.5  (8.54) -18.1  (9.14)
9.Secondary Outcome
Title Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing (FEES) for Texture Utilized at Week 40
Hide Description The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. FEES for texture utilized was evaluated. Data was presented only for the shifts observed.
Time Frame Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Thin Liquids to Thin Liquids
2
  33.3%
2
  33.3%
2
  33.3%
4
  66.7%
Thin Liquids to Thickened Liquids
1
  16.7%
2
  33.3%
0
   0.0%
0
   0.0%
Thin Liquids to Puree Texture
1
  16.7%
2
  33.3%
1
  16.7%
4
  66.7%
Thin Liquids to Solids
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
Thickened Liquids to Thin Liquids
1
  16.7%
2
  33.3%
1
  16.7%
1
  16.7%
Thickened Liquids to Thickened Liquids
0
   0.0%
2
  33.3%
3
  50.0%
0
   0.0%
Thickened Liquids to Puree Texture
1
  16.7%
2
  33.3%
3
  50.0%
1
  16.7%
Thickened Liquids to Solids
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
Puree Texture to Thin Liquids
1
  16.7%
2
  33.3%
3
  50.0%
2
  33.3%
Puree Texture to Thickened Liquids
1
  16.7%
2
  33.3%
2
  33.3%
0
   0.0%
Puree Texture to Puree Texture
3
  50.0%
4
  66.7%
4
  66.7%
3
  50.0%
Puree Texture to Solids
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
Solids to Thin Liquids
0
   0.0%
2
  33.3%
0
   0.0%
1
  16.7%
Solids to Thickened Liquids
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
Solids to Puree Texture
0
   0.0%
2
  33.3%
0
   0.0%
1
  16.7%
Solids to Solids
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
10.Secondary Outcome
Title Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Laryngeal Penetration) at Week 40
Hide Description The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. Feeding assessment for laryngeal penetration was assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture, WCC refers to with cough and clearance and WCNC refers to with cough and no clearance.
Time Frame Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Normal to Normal (TL)
0
   0.0%
0
   0.0%
2
  33.3%
1
  16.7%
Normal to Without Cough (TL)
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
Without Cough to Without Cough (TL)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
WCC to Without Cough (TL)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
WCC to WCC (TL)
0
   0.0%
2
  33.3%
0
   0.0%
1
  16.7%
Normal to WCC (THL)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Without Cough to Normal (THL)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
WCC to Normal (THL)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
WCC to WCC (THL)
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
Normal to Normal (PT)
0
   0.0%
1
  16.7%
1
  16.7%
1
  16.7%
Normal to WCC (PT)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Normal to WCNC (PT)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
Without Cough to Normal (PT)
0
   0.0%
0
   0.0%
2
  33.3%
0
   0.0%
Without Cough to WCC (PT)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
WCC to Normal (PT)
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
WCC to WCC (PT)
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
WCNC to Normal (PT)
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
WCNC to Without Cough (PT)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
WCC to WCC (Solids) NA [1] 
2
  33.3%
NA [1]  NA [1] 
[1]
Data was not available for this texture as the assessment was considered normal.
11.Secondary Outcome
Title Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Feeding Assessment (Aspiration Through Vocal Cords) at Week 40
Hide Description The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. Feeding assessment for aspiration through vocal cords were assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture, WCC refers to with cough and clearance and WCNC refers to with cough and no clearance.
Time Frame Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Normal to Normal (TL)
0
   0.0%
0
   0.0%
2
  33.3%
3
  50.0%
Without Cough to Without Cough (TL)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
WCC to WCC (TL)
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
Normal to Normal (THL)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Without Cough to Normal (THL)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
WCC to Normal (THL)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
WCC to WCC (THL)
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
Normal to Normal (PT)
0
   0.0%
2
  33.3%
2
  33.3%
2
  33.3%
Without Cough to Normal (PT)
0
   0.0%
0
   0.0%
2
  33.3%
0
   0.0%
WCC to WCC (PT)
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
WCNC to Normal (PT)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
WCC to WCC (Solids) NA [1] 
2
  33.3%
NA [1]  NA [1] 
[1]
Data was not available for this texture as the assessment was considered normal.
12.Secondary Outcome
Title Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Dose Residue Clear After Subsequent Swallowing at Week 40
Hide Description The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. FEES for dose residue clear after subsequent swallowing was assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture.
Time Frame Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Normal to Normal (TL)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Normal to Yes (TL)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Yes to Yes (TL)
1
  16.7%
2
  33.3%
0
   0.0%
1
  16.7%
Yes to No (TL)
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
No to Yes (TL)
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
No to No (TL)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
Normal to Yes (THL)
0
   0.0%
0
   0.0%
2
  33.3%
0
   0.0%
Yes to Normal (THL)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Yes to Yes (THL)
0
   0.0%
2
  33.3%
0
   0.0%
0
   0.0%
Normal to Normal (PT)
0
   0.0%
1
  16.7%
0
   0.0%
1
  16.7%
Normal to Yes (PT)
0
   0.0%
0
   0.0%
2
  33.3%
0
   0.0%
Normal to No (PT)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
Yes to Normal (PT)
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Yes to Yes (PT)
1
  16.7%
2
  33.3%
0
   0.0%
1
  16.7%
Yes to No (PT)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
No to Normal (PT)
0
   0.0%
1
  16.7%
1
  16.7%
0
   0.0%
Yes to Yes (Solids) NA [1] 
2
  33.3%
NA [1]  NA [1] 
[1]
Data was not available for this texture as the assessment was considered normal.
13.Secondary Outcome
Title Number of Participants With Shift in Functional Endoscopic Evaluation of Swallowing for Aspiration Risk at Week 40
Hide Description The FEES assessment was performed to evaluate the structure and function of the upper throat during swallowing and for an assessment of aspiration risk. Each participant had this assessment performed at the clinical site using transnasal flexible laryngoscopy. FEES for aspiration risk was assessed. Data was presented only for the shifts observed. Here TL refers to thin liquids, THL refers to thickened liquids, PT refers to puree texture, WCC refers to with cough and clearance and WCNC refers to with cough and no clearance.
Time Frame Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Low to Low (TL)
2
  33.3%
2
  33.3%
2
  33.3%
3
  50.0%
Low to High (TL)
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
Low to Low (THL)
0
   0.0%
2
  33.3%
3
  50.0%
0
   0.0%
Low to Low (PT)
1
  16.7%
3
  50.0%
3
  50.0%
3
  50.0%
Low to High (PT)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
Moderate to Low (PT)
0
   0.0%
1
  16.7%
1
  16.7%
0
   0.0%
Moderate to Moderate (PT)
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
Low to Low (Solids) NA [1] 
2
  33.3%
NA [1]  NA [1] 
[1]
Data was not available for this texture as the assessment was considered normal.
14.Secondary Outcome
Title Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Amplitude Values at Week 40
Hide Description Evaluation of peripheral nerve function by ENG studies was performed to measure nerve conduction velocity (NCV), amplitude (AMP),distal latency (DL), and F-wave latency. Categorized amplitude values were assessed. Data was presented only for number of participants who reported change in amplitude greater than (>) 0.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Median Motor Wrist Amplitude (Baseline)
6
 100.0%
5
  83.3%
5
  83.3%
6
 100.0%
Median Motor Wrist Amplitude (Week 40)
3
  50.0%
5
  83.3%
6
 100.0%
5
  83.3%
Median Motor Elbow Amplitude (Baseline)
0
   0.0%
2
  33.3%
4
  66.7%
6
 100.0%
Median Motor Elbow Amplitude (Week 40)
0
   0.0%
4
  66.7%
6
 100.0%
4
  66.7%
Median Sensory Wrist Amplitude (Baseline)
2
  33.3%
3
  50.0%
4
  66.7%
4
  66.7%
Median Sensory Wrist Amplitude (Week 40)
1
  16.7%
5
  83.3%
3
  50.0%
3
  50.0%
Peroneal Motor Fibular Head Amplitude (Baseline)
0
   0.0%
2
  33.3%
4
  66.7%
6
 100.0%
Peroneal Motor Fibular Head Amplitude (Week 40)
0
   0.0%
4
  66.7%
5
  83.3%
4
  66.7%
Peroneal Motor Ankle Amplitude (Baseline)
6
 100.0%
5
  83.3%
5
  83.3%
6
 100.0%
Peroneal Motor Ankle Amplitude (Week 40)
4
  66.7%
5
  83.3%
5
  83.3%
4
  66.7%
Sural Sensory B-point (Baseline)
2
  33.3%
2
  33.3%
3
  50.0%
4
  66.7%
Sural Sensory B-point (Week 40)
2
  33.3%
2
  33.3%
3
  50.0%
4
  66.7%
Tibial Motor Ankle Amplitude (Baseline)
4
  66.7%
3
  50.0%
3
  50.0%
3
  50.0%
Tibial Motor Ankle Amplitude (Week 40)
2
  33.3%
3
  50.0%
4
  66.7%
1
  16.7%
Tibial Motor Knee Amplitude (Baseline)
0
   0.0%
0
   0.0%
3
  50.0%
3
  50.0%
Tibial Motor Knee Amplitude (Week 40)
0
   0.0%
2
  33.3%
4
  66.7%
1
  16.7%
Ulnar Motor Wrist Amplitude (Baseline)
4
  66.7%
3
  50.0%
3
  50.0%
3
  50.0%
Ulnar Motor Wrist Amplitude (Week 40)
2
  33.3%
3
  50.0%
3
  50.0%
1
  16.7%
Ulnar Motor Elbow Amplitude (Baseline)
0
   0.0%
0
   0.0%
3
  50.0%
3
  50.0%
Ulnar Motor Elbow Amplitude (Week 40)
0
   0.0%
2
  33.3%
3
  50.0%
1
  16.7%
15.Secondary Outcome
Title Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Nerve Conduction Velocity at Week 40
Hide Description Evaluation of peripheral nerve function by ENG studies was performed to measure nerve conduction velocity (NCV), amplitude (AMP),distal latency (DL), and F-wave latency. Categorized nerve conduction velocity values were assessed. Data was presented only for number of participants who reported change in nerve conduction velocity > 0. Here MME refers to median motor elbow, WCV for wrist conduction velocity, PMA for peroneal motor ankle, FHCV to fibular head conduction velocity, TMA for tibial motor ankle, KCV for knee conduction velocity and UME for ulnar motor elbow,
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
MME to WCV (Baseline)
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
MME to WCV (Week 40)
3
  50.0%
5
  83.3%
6
 100.0%
5
  83.3%
PMA to FHCV (Baseline)
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
PMA to FHCV (Week 40)
4
  66.7%
5
  83.3%
5
  83.3%
4
  66.7%
TMA to KCV (Baseline)
4
  66.7%
4
  66.7%
4
  66.7%
3
  50.0%
TMA to KCV (Week 40)
2
  33.3%
3
  50.0%
4
  66.7%
1
  16.7%
UME to WCV (Baseline)
4
  66.7%
4
  66.7%
4
  66.7%
3
  50.0%
UME to WCV (Week 40)
2
  33.3%
3
  50.0%
3
  50.0%
1
  16.7%
16.Secondary Outcome
Title Number of Participants With Change in Nerve Conduction as Measured by Electroneurography (ENG) Assessments by Categorized Distal Latency at Week 40
Hide Description Evaluation of peripheral nerve function by ENG studies was performed to measure nerve conduction velocity (NCV), amplitude (AMP),distal latency (DL), and F-wave latency. Categorized amplitude values were assessed. Data was presented only for number of participants who reported change in distal latency > 0. Here MMW refers to median motor wrist, APB for abductor pollicis brevis, MSW for median sensory wrist, DDL for digit distal latency, PMA for peroneal motor ankle, EDB for extensor digitorum brevis, SSB-point DL for sural sensory B-point distal latency, TMA for tibial motor ankle, abductor hallucis for AH distal latency and, UMW for ulnar motor wrist.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
MMW to APB distal latency (Baseline)
6
 100.0%
5
  83.3%
5
  83.3%
6
 100.0%
MMW to APB distal latency (Week 40)
3
  50.0%
5
  83.3%
6
 100.0%
5
  83.3%
MSW to DDL (Baseline)
0
   0.0%
1
  16.7%
2
  33.3%
3
  50.0%
MSW to DDL (Week 40)
0
   0.0%
3
  50.0%
2
  33.3%
3
  50.0%
PMA to EDB Distal Latency (Baseline)
6
 100.0%
5
  83.3%
5
  83.3%
6
 100.0%
PMA to EDB Distal Latency (Week 40)
4
  66.7%
5
  83.3%
5
  83.3%
3
  50.0%
SS B-Point Distal Latency (Baseline)
2
  33.3%
2
  33.3%
2
  33.3%
3
  50.0%
SS B-Point Distal Latency (Week 40)
1
  16.7%
2
  33.3%
1
  16.7%
4
  66.7%
TMA to AH Distal Latency (Baseline)
0
   0.0%
0
   0.0%
3
  50.0%
3
  50.0%
TMA to AH Distal Latency (Week 40)
0
   0.0%
2
  33.3%
4
  66.7%
0
   0.0%
UMW to ADM Distal Latency (Baseline)
4
  66.7%
3
  50.0%
3
  50.0%
3
  50.0%
UMW to ADM Distal Latency (Week 40)
2
  33.3%
3
  50.0%
3
  50.0%
1
  16.7%
17.Secondary Outcome
Title Change From Baseline in Adaptive Behavior Composite Standard Score as Measured by Vineland Adaptive Behavior Scales, Second Edition (VABS-II) at Week 40
Hide Description The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. This test measures the following 4 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (ABC) (a composite of the other 4 domain). Items in each domain are rated as either 0 (does not), 1(sometimes) or 2(independently) performs a given behavior or skill. The 4 domain standard scores range from 20-160 and higher scores indicate a higher level of functioning. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160) and higher scores indicate a higher level of functioning. A positive change value indicates improvement in adaptive functioning.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery. Participants from SHP611 10 mg and SHP611 30 mg were excluded from the analysis. Since, analysis was planned for participants received SHP611 100 mg with different manufacturing processes (Process A and B).
Arm/Group Title SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Communication(Baseline) Number Analyzed 1 participants 3 participants
52.0 [1]   (NA) 97.3  (2.52)
Communication(Week 40) Number Analyzed 1 participants 3 participants
-10.0 [1]   (NA) -25.0  (18.19)
Daily Living Skills(Baseline) Number Analyzed 2 participants 3 participants
49.0  (1.41) 80.3  (9.02)
Daily Living Skills(Week 40) Number Analyzed 2 participants 3 participants
-4.0  (5.66) -27.0  (19.47)
Socialization(Baseline) Number Analyzed 2 participants 3 participants
50.0  (1.41) 86.0  (3.61)
Socialization(Week 40) Number Analyzed 2 participants 3 participants
-0.5  (0.71) -18.0  (17.09)
Motor Skills(Baseline) Number Analyzed 2 participants 3 participants
31.0  (0.00) 83.7  (24.83)
Motor Skills(Week 40) Number Analyzed 2 participants 3 participants
6.0  (16.97) -43.3  (23.18)
Adaptive Behavior CSS(Baseline) Number Analyzed 1 participants 3 participants
43.0 [1]   (NA) 84.0  (10.54)
Adaptive Behavior CSS(Week 40) Number Analyzed 1 participants 3 participants
-5.0 [1]   (NA) -25.3  (16.44)
[1]
Standard deviation was not calculated due to insufficient number of participants.
18.Secondary Outcome
Title Change From Baseline in Domain-specific Caregiver Observed Metachromatic Leukodystrophy (MLD) Functioning and Outcomes Reporting Tool (COMFORT) Scores at Week 40
Hide Description COMFORT questionnaire was used to assess health status and the impact of disease on the ability of participants with MLD to carry out activities of daily life. The questionnaire was organized by 8 domains (ie, personal care; positioning, transfer, or mobility; eating; pain and discomfort during the day; sleep; emotions; communication; and play and leisure activities). The COMFORT scores range from 0 to 100, with higher scores indicating a decline in the functioning.
Time Frame Baseline, Week 40
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set consisted of participants who received at least 1 dose of investigational product or underwent device implant surgery. Participants from SHP611 10 mg and SHP611 30 mg were excluded from the analysis. Since, analysis was planned for participants received SHP611 100 mg with different manufacturing processes (Process A and B).
Arm/Group Title SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Communication (Baseline) Number Analyzed 5 participants 6 participants
27.3  (13.27) 16.9  (8.65)
Communication (Week 40) Number Analyzed 5 participants 6 participants
24.7  (26.81) 21.4  (20.92)
Eating difficulty (Baseline) Number Analyzed 5 participants 6 participants
21.1  (22.94) 2.4  (5.77)
Eating difficulty (Week 40) Number Analyzed 5 participants 6 participants
25.1  (22.44) 11.8  (10.29)
Emotions (Baseline) Number Analyzed 5 participants 6 participants
60.0  (9.13) 55.6  (12.55)
Emotions (Week 40) Number Analyzed 5 participants 6 participants
-15.0  (21.57) -1.4  (6.27)
Pain and discomfort during the day (Baseline) Number Analyzed 5 participants 6 participants
16.6  (10.16) 6.9  (11.05)
Pain and discomfort during the day (Week 40) Number Analyzed 5 participants 6 participants
13.5  (15.23) 0.0  (11.74)
Personal care (Baseline) Number Analyzed 5 participants 6 participants
48.0  (21.26) 36.0  (17.99)
Personal care (Week 40) Number Analyzed 5 participants 6 participants
18.1  (37.94) 7.3  (18.95)
Play and leisure activities (Baseline) Number Analyzed 5 participants 6 participants
46.0  (19.81) 16.7  (16.33)
Play and leisure activities (Week 40) Number Analyzed 5 participants 6 participants
1.0  (28.15) 30.0  (25.88)
Positioning, transfer or mobility (Baseline) Number Analyzed 5 participants 6 participants
42.2  (19.44) 18.0  (18.80)
Positioning, transfer or mobility (Week 40) Number Analyzed 5 participants 6 participants
6.7  (21.82) 8.8  (13.14)
Sleep (Baseline) Number Analyzed 5 participants 6 participants
11.9  (5.52) 18.9  (6.52)
Sleep (Week 40) Number Analyzed 5 participants 6 participants
6.8  (17.08) 4.5  (15.60)
19.Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of SHP611
Hide Description Cmax is the maximum observed serum concentration of SHP611.
Time Frame Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Nanogram per milliliter (ng/mL)
Baseline Number Analyzed 6 participants 6 participants 6 participants 5 participants
214.53  (162.104) 500.83  (260.978) 715.17  (339.856) 799.60  (494.452)
Week 38 Number Analyzed 2 participants 5 participants 4 participants 4 participants
157.50  (36.062) 275.40  (156.329) 888.75  (225.457) 1494.83  (1297.295)
20.Secondary Outcome
Title Time to Reach Maximum Observed Drug Concentration (Tmax) of SHP611 in Plasma
Hide Description Tmax is the time to reach maximum observed drug concentration of SHP611 during a dosing interval.
Time Frame Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Hour (h)
Baseline Number Analyzed 6 participants 6 participants 6 participants 5 participants
7.06  (1.086) 6.81  (3.462) 5.97  (4.802) 9.61  (8.344)
Week 38 Number Analyzed 2 participants 5 participants 4 participants 4 participants
5.08  (1.450) 11.22  (1.780) 18.16  (11.661) 7.02  (3.824)
21.Secondary Outcome
Title Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of SHP611
Hide Description The AUC0-inf is the area under the concentration-time curve from time zero to infinity of SHP611.
Time Frame Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Hour * nanogram/milliliter (h*ng/mL)
Baseline Number Analyzed 1 participants 4 participants 2 participants 3 participants
4355 [1]   (NA) 10105  (3307.4) 22123  (4217.4) 23117  (10380.1)
Week 38 Number Analyzed 1 participants 1 participants 0 participants 2 participants
2767 [1]   (NA) 9589 [1]   (NA) 48648  (6906.8)
[1]
Standard deviation was not calculated due to insufficient number of participants.
22.Secondary Outcome
Title Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of SHP611
Hide Description AUC0-last is the area under the concentration-time curve from the time of dosing to the last measurable concentration of SHP611.
Time Frame Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: hour * nanogram per milliliter (h*ng/mL)
Baseline Number Analyzed 6 participants 6 participants 6 participants 5 participants
2532  (1178.4) 8738  (3106.4) 15022  (10755.2) 16288  (10691.4)
Week 38 Number Analyzed 2 participants 5 participants 4 participants 4 participants
1972  (211.5) 6156  (3904.5) 24820  (16954.3) 29219  (21261.5)
23.Secondary Outcome
Title Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of SHP611
Hide Description Area under the concentration-time curve over the interval from 0 to 24 hours after dosing of SHP611.
Time Frame Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: hour * nanogram per milliliter (h*ng/mL)
Baseline Number Analyzed 6 participants 6 participants 5 participants 5 participants
2530  (1178.0) 6258  (2995.3) 11918  (6376.1) 13114  (8012.0)
Week 38 Number Analyzed 2 participants 4 participants 3 participants 3 participants
1960  (224.0) 4596  (2316.1) 18264  (2162.7) 31115  (15805.6)
24.Secondary Outcome
Title First Order Rate Constant (Lambda z) Associated With the Terminal (Log-linear) Portion of the Curve for SHP611
Hide Description Lambda z is first order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
Time Frame Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Per hour (/h)
Baseline Number Analyzed 1 participants 4 participants 2 participants 3 participants
0.0934 [1]   (NA) 0.0561  (0.01900) 0.0461  (0.02439) 0.0607  (0.01949)
Week 38 Number Analyzed 1 participants 1 participants 0 participants 2 participants
0.0506 [1]   (NA) 0.0640 [1]   (NA) 0.0857  (0.04415)
[1]
Standard deviation was not calculated due to insufficient number of participants.
25.Secondary Outcome
Title Terminal Elimination Half Life (t1/2) of SHP611
Hide Description The t1/2 is the time in hours required for the concentration of the drug to reach half of its original value.
Time Frame Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Hour (h)
Baseline Number Analyzed 1 participants 4 participants 2 participants 3 participants
7.42 [1]   (NA) 13.60  (4.932) 17.47  (9.238) 12.34  (4.373)
Week 38 Number Analyzed 1 participants 1 participants 0 participants 2 participants
13.70 [1]   (NA) 10.83 [1]   (NA) 9.32  (4.800)
[1]
Standard deviation was not calculated due to insufficient number of participants.
26.Secondary Outcome
Title Total Body Clearance (CL/F) After Intrathecal Administration of SHP611
Hide Description CL/F was defined as the total body clearance of the drug for extravascular administration divided by the fraction of dose absorbed.
Time Frame Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Liter per hour (L/h)
Baseline Number Analyzed 1 participants 4 participants 2 participants 3 participants
2.30 [1]   (NA) 3.25  (1.185) 4.60  (0.878) 5.28  (3.179)
Week 38 Number Analyzed 1 participants 1 participants 0 participants 2 participants
3.61 [1]   (NA) 3.13 [1]   (NA) 2.08  (0.295)
[1]
Standard deviation was not calculated due to insufficient number of participants.
27.Secondary Outcome
Title Volume of Distribution (Vz/F) After Intrathecal Administration of SHP611
Hide Description Volume of distribution was associated with the terminal slope following extravascular administration of SHP611 divided by the fraction of dose absorbed.
Time Frame Baseline: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose; Week 38: Predose, 0.5, 1, 2, 4, 8, 12, 24, 48 hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Liter (L)
Baseline Number Analyzed 1 participants 4 participants 2 participants 3 participants
24.58 [1]   (NA) 69.97  (49.912) 121.88  (83.481) 106.95  (100.026)
Week 38 Number Analyzed 1 participants 1 participants 0 participants 2 participants
71.41 [1]   (NA) 48.88 [1]   (NA) 28.95  (18.345)
[1]
Standard deviation was not calculated due to insufficient number of participants.
28.Secondary Outcome
Title Concentration of SHP611 in Cerebrospinal Fluid
Hide Description Concentration of SHP611 in CSF was determined using validated enzyme-linked immunosorbent assay (ELISA) method.
Time Frame Baseline, 4, 8, 12, 16, 20, 24, 28, 32, 36, and 40 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
PK set consisted of participants who received at least 1 dose of investigational product and had at least 1 measurable serum concentration or 1 measurable CSF concentration of SHP611.
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description:
Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the original drug substance manufacturing process referred to as Process A.
Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. In this cohort, participants received SHP611 produced with the revised drug substance manufacturing process referred to as Process B.
Overall Number of Participants Analyzed 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Nanogram per milliliter (ng/mL)
Baseline Number Analyzed 6 participants 6 participants 6 participants 5 participants
280.00  (685.857) 0  (0) 0  (0) 0  (0)
Week 4 Number Analyzed 6 participants 6 participants 6 participants 4 participants
182.93  (165.913) 78.00  (102.516) 2935.17  (2632.398) 6152.50  (6546.986)
Week 8 Number Analyzed 6 participants 6 participants 5 participants 4 participants
85.47  (79.316) 1854.07  (2633.858) 4171.20  (4874.122) 3825.00  (2182.056)
Week 12 Number Analyzed 5 participants 6 participants 6 participants 5 participants
57.50  (57.365) 1556.17  (1557.666) 2310.00  (2544.814) 2304.00  (2155.558)
Week 16 Number Analyzed 6 participants 6 participants 6 participants 5 participants
93.83  (147.188) 2805.68  (3499.878) 2395.00  (1550.648) 2606.20  (1212.857)
Week 20 Number Analyzed 6 participants 6 participants 6 participants 3 participants
112.78  (143.216) 1364.65  (2784.474) 5182.50  (5081.080) 4423.33  (4195.406)
Week 24 Number Analyzed 6 participants 6 participants 6 participants 5 participants
132.57  (235.783) 802.67  (903.025) 5402.50  (7352.246) 7914.60  (8243.114)
Week 28 Number Analyzed 5 participants 6 participants 6 participants 4 participants
525.06  (874.710) 3274.62  (4493.212) 6273.83  (6839.101) 3682.58  (4331.130)
Week 32 Number Analyzed 5 participants 6 participants 5 participants 5 participants
70.12  (126.513) 573.62  (376.224) 1831.40  (988.294) 6110.00  (4099.500)
Week 36 Number Analyzed 5 participants 6 participants 6 participants 3 participants
72.40  (125.574) 1046.05  (1087.321) 3917.50  (4650.791) 3116.67  (336.502)
Week 40 Number Analyzed 6 participants 2 participants 6 participants 4 participants
659.15  (1602.414) 243.60  (313.107) 2931.83  (4098.389) 6663.75  (7947.148)
Time Frame From start of study treatment up to safety follow up (Week 42)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Hide Arm/Group Description Participants received 10 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. Participants received 30 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks. Participants received 100 mg dose of SHP611 (HGT-1110, rhASA) EOW by IDDD for 38 weeks.
All-Cause Mortality
SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/6 (0.00%)    
Hide Serious Adverse Events
SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/6 (83.33%)      4/6 (66.67%)      3/6 (50.00%)      2/6 (33.33%)    
Gastrointestinal disorders         
Vomiting * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
General disorders         
Device dislocation * 1  1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Device failure * 1  2/6 (33.33%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Device malfunction * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Device occlusion * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Implant site effusion * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  3 0/6 (0.00%)  0
Pain * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Pyrexia * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Infections and infestations         
Gastroenteritis * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Gastroenteritis viral * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Implant site infection * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Influenza * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Nasopharyngitis * 1  2/6 (33.33%)  2 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Pneumonia * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Respiratory tract infection viral * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0
Urinary tract infection * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Viral infection * 1  1/6 (16.67%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Viral pharyngitis * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Viral upper respiratory tract infection * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0
Investigations         
Alanine aminotransferase increased * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Aspartate aminotransferase increased * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Gamma-Glutamyltransferase increased * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Nervous system disorders         
Convulsion * 1  0/6 (0.00%)  0 1/6 (16.67%)  3 0/6 (0.00%)  0 1/6 (16.67%)  1
Febrile convulsion * 1  1/6 (16.67%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1
Muscle spasticity * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Aspiration * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
1
Term from vocabulary, MedDRA 15.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
SHP611 10 mg (Process A) SHP611 30 mg (Process A) SHP611 100 mg (Process A) SHP611 100 mg (Process B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/6 (100.00%)      6/6 (100.00%)      6/6 (100.00%)      6/6 (100.00%)    
Blood and lymphatic system disorders         
Eosinophilia * 1  0/6 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Leukocytosis * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Lymphopenia * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Congenital, familial and genetic disorders         
Phimosis * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Talipes * 1  2/6 (33.33%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Ear and labyrinth disorders         
Ear haemorrhage * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Ear pain * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Eye disorders         
Conjunctivitis * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Eye swelling * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Visual acuity reduced * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Gastrointestinal disorders         
Abdominal pain upper * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Anal fissure * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Constipation * 1  3/6 (50.00%)  4 4/6 (66.67%)  7 3/6 (50.00%)  3 4/6 (66.67%)  5
Diarrhoea * 1  2/6 (33.33%)  3 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1
Dysphagia * 1  2/6 (33.33%)  2 1/6 (16.67%)  2 1/6 (16.67%)  2 0/6 (0.00%)  0
Gastrooesophageal reflux disease * 1  1/6 (16.67%)  1 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Gingivitis * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Nausea * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 3/6 (50.00%)  4 1/6 (16.67%)  1
Pancreatitis * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Salivary duct obstruction * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Salivary hypersecretion * 1  1/6 (16.67%)  1 2/6 (33.33%)  2 1/6 (16.67%)  1 0/6 (0.00%)  0
Stomatitis * 1  0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Vomiting * 1  4/6 (66.67%)  5 5/6 (83.33%)  7 4/6 (66.67%)  11 2/6 (33.33%)  6
General disorders         
Asthenia * 1  1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Complication of device removal * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Crying * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Device dislocation * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Device malfunction * 1  3/6 (50.00%)  3 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Discomfort * 1  0/6 (0.00%)  0 1/6 (16.67%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0
Disease progression * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2
Gait disturbance * 1  0/6 (0.00%)  0 2/6 (33.33%)  4 0/6 (0.00%)  0 0/6 (0.00%)  0
Implant site cyst * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Implant site effusion * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 3/6 (50.00%)  6 1/6 (16.67%)  1
Implant site pain * 1  3/6 (50.00%)  4 2/6 (33.33%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Pain * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Pyrexia * 1  5/6 (83.33%)  15 3/6 (50.00%)  17 5/6 (83.33%)  6 5/6 (83.33%)  11
Hepatobiliary disorders         
Cytolytic hepatitis * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Immune system disorders         
Seasonal allergy * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Infections and infestations         
Acute tonsillitis * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  3
Bronchitis * 1  2/6 (33.33%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Cystitis * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Ear infection * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Enterovirus infection * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Febrile infection * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Gastroenteritis * 1  2/6 (33.33%)  2 1/6 (16.67%)  1 0/6 (0.00%)  0 2/6 (33.33%)  2
Gastroenteritis viral * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Impetigo * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Implant site infection * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Influenza * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Lung infection * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0
Nasopharyngitis * 1  4/6 (66.67%)  6 1/6 (16.67%)  1 1/6 (16.67%)  1 1/6 (16.67%)  2
Oral candidiasis * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Otitis media * 1  0/6 (0.00%)  0 2/6 (33.33%)  3 0/6 (0.00%)  0 1/6 (16.67%)  1
Respiratory tract infection viral * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Rhinitis * 1  2/6 (33.33%)  3 2/6 (33.33%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0
Tonsillitis * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Upper respiratory tract infection * 1  1/6 (16.67%)  1 3/6 (50.00%)  5 1/6 (16.67%)  1 2/6 (33.33%)  5
Urinary tract infection * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Viral infection * 1  1/6 (16.67%)  2 0/6 (0.00%)  0 2/6 (33.33%)  3 0/6 (0.00%)  0
Viral pharyngitis * 1  1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Viral upper respiratory tract infection * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2 1/6 (16.67%)  1
Injury, poisoning and procedural complications         
Contusion * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Endotracheal intubation complication * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Fall * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1
Incision site oedema * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Laceration * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Post procedural complication * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Post procedural oedema * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Postoperative fever * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0
Postoperative wound complication * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Procedural pain * 1  2/6 (33.33%)  2 2/6 (33.33%)  2 3/6 (50.00%)  3 5/6 (83.33%)  5
Vaccination complication * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Wrong technique in drug usage process * 1  3/6 (50.00%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Investigations         
Alanine aminotransferase increased * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Albumin csf increased * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Amylase increased * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Aspartate aminotransferase increased * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Blood alkaline phosphatase increased * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Blood creatine phosphokinase increased * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/6 (50.00%)  4
Blood iron decreased * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Blood pressure increased * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Body temperature increased * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1
Csf lymphocyte count increased * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  2
Csf mononuclear cell count increased * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Csf protein increased * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Csf white blood cell count increased * 1  1/6 (16.67%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Eosinophil count increased * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  2 0/6 (0.00%)  0
Gamma-Glutamyltransferase increased * 1  2/6 (33.33%)  4 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Hepatic enzyme increased * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Mean cell volume decreased * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Neutrophil count increased * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Red blood cells csf positive * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0
Weight decreased * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
White blood cell count increased * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Metabolism and nutrition disorders         
Dehydration * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Iron deficiency * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Musculoskeletal and connective tissue disorders         
Back pain * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Kyphosis * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Lordosis * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Muscle spasms * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Pain in extremity * 1  3/6 (50.00%)  3 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Tendinous contracture * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Tendon disorder * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Tendonitis * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Nervous system disorders         
Akathisia * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Areflexia * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Ataxia * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Cerebellar syndrome * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Clonus * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Convulsion * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1
Disturbance in attention * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Drooling * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Dysarthria * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Dystonia * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Epilepsy * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Febrile convulsion * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1
Headache * 1  1/6 (16.67%)  1 1/6 (16.67%)  1 2/6 (33.33%)  2 2/6 (33.33%)  2
Hypotonia * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Motor dysfunction * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Muscle spasticity * 1  4/6 (66.67%)  4 2/6 (33.33%)  3 1/6 (16.67%)  1 2/6 (33.33%)  2
Myoclonus * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Neuralgia * 1  2/6 (33.33%)  3 3/6 (50.00%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0
Speech disorder * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Speech disorder developmental * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Psychiatric disorders         
Abnormal behaviour * 1  0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0
Agitation * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Decreased eye contact * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Initial insomnia * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Insomnia * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Restlessness * 1  0/6 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1
Sleep disorder * 1  3/6 (50.00%)  3 1/6 (16.67%)  1 0/6 (0.00%)  0 2/6 (33.33%)  3
Renal and urinary disorders         
Proteinuria * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Urinary incontinence * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Urinary retention * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Reproductive system and breast disorders         
Balanitis * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Vulvovaginal erythema * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Aspiration * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Bronchial obstruction * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Choking * 1  0/6 (0.00%)  0 2/6 (33.33%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0
Cough * 1  1/6 (16.67%)  2 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Epistaxis * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1
Laryngeal inflammation * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 2/6 (33.33%)  2 0/6 (0.00%)  0
Nasal obstruction * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0
Oropharyngeal pain * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Pharyngeal erythema * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Rhinitis allergic * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Rhinorrhoea * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Sleep apnoea syndrome * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Sneezing * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Tonsillar hypertrophy * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Wheezing * 1  0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0
Skin and subcutaneous tissue disorders         
Eczema * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1
Erythema nodosum * 1  1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0
Hirsutism * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Keloid scar * 1  0/6 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0
Rash * 1  2/6 (33.33%)  3 2/6 (33.33%)  3 0/6 (0.00%)  0