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Trial record 1 of 2 for:    SGS-742
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Phase 2 Clinical Trial of SGS-742 Therapy in Succinic Semialdehyde Dehydrogenase Deficiency

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ClinicalTrials.gov Identifier: NCT02019667
Recruitment Status : Completed
First Posted : December 24, 2013
Results First Posted : February 24, 2020
Last Update Posted : February 24, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Metabolic Disease
Seizures
Interventions Drug: SGS-742
Drug: Placebo
Enrollment 19
Recruitment Details Participants were recruited and enrolled in the protocol between March 2014 and October 2017, with assistance from referring physicians in the community and the SSADH foundation. A total of 19 participants were enrolled; 16 completed dosing in both placebo and active drug arms.
Pre-assignment Details Following a baseline visit, participants were randomized to receive either placebo or study drug for 6 months (Phase 1) followed by 6 months of the alternate treatment (Phase 2). Participants completed a 9-week washout period following each phase of the study.
Arm/Group Title Placebo First, Then SGS-742 SGS-742 First, Then Placebo
Hide Arm/Group Description Participants were administered Placebo, followed by a washout period, and then administered SGS-742 Participants were administered SGS-742, followed by a washout period, and then administered Placebo
Period Title: First Intervention (6 Months)
Started 10 9
Completed 10 8
Not Completed 0 1
Reason Not Completed
Adverse Event             0             1
Period Title: Washout Period (9 Weeks)
Started 10 8
Completed 10 8
Not Completed 0 0
Period Title: 2nd Intervention (6 Months)
Started 10 8
Completed 10 6
Not Completed 0 2
Reason Not Completed
Adverse Event             0             1
Physician Decision             0             1
Period Title: Washout Period (9 Weeks)
Started 10 6
Completed 10 6
Not Completed 0 0
Arm/Group Title All Study Participants
Hide Arm/Group Description Participants with SSADH Deficiency who were randomized to receive either SGS-742 or Placebo
Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants
14  (7.31)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
11
  57.9%
Male
8
  42.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Hispanic or Latino
1
   5.3%
Not Hispanic or Latino
18
  94.7%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Change From Baseline on the Adaptive Behavior Assessment System (ABAS) Test at the End of the Study Drug and Placebo Treatment Periods
Hide Description The ABAS questionnaire was completed by the participant's parent or caregiver at the end of each six month treatment period.The ABAS provides a comprehensive picture of adaptive skills across the lifespan. The questionnaire addresses Conceptual, Social and Practical skills including communication, self-direction, use of leisure time, health, safety and self-care. The General Adaptive Composite score ranges from <40 to >160 with a lower score representing lower adaptive behavior. The difference between Placebo and Baseline and Study Drug and Baseline were obtained. These values were averaged across individuals to report a mean and a standard deviation of the baseline-to-treatment period change. The means for each treatment can be compared to have a baseline-adjusted treatment effect interpretation. A positive change represents an improvement in adaptive skills compared with baseline and a negative change represents a decline in adaptive skills compared with baseline.
Time Frame baseline and six months
Hide Outcome Measure Data
Hide Analysis Population Description
The ABAS was not able to be completed for all participants.
Arm/Group Title Placebo Study Drug
Hide Arm/Group Description:

Participants with SSADH Deficiency when on placebo for six months

Placebo

Participants with SSADH Deficiency receiving SGS-742 when on study drug for six months

SGS-742
Overall Number of Participants Analyzed 13 13
Mean (Standard Deviation)
Unit of Measure: scores on a scale
5.2  (7.1) 4.5  (7.5)
2.Secondary Outcome
Title Change From Baseline of TMS Measurement of Motor Threshold at the End of the Study Drug and Placebo Treatment Periods
Hide Description Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons. The motor threshold is defined as the minimum percentage of the stimulator output that evoked a motor evoked potential of more than 50µV in at least 5 out of 10 trials. Motor threshold was measured at the end of the study drug period and the end of the Placebo period. The differences between Placebo and Baseline, and SGS and Baseline were obtained. A decrease from baseline value indicates increased cortical excitability and an increase from baseline value indicates reduced cortical excitability. These values were averaged across individuals to report a mean and standard deviation of this baseline-to-treatment period change. The mean for each treatment can be compared to have a baseline-adjusted treatment effect.
Time Frame Baseline and Six months
Hide Outcome Measure Data
Hide Analysis Population Description
We were unable to obtain Motor Thresholds for all participants at all three timepoints, resulting in different N for each time period. All available data is reported.
Arm/Group Title Placebo Study Drug
Hide Arm/Group Description:

Participants with SSADH Deficiency when on placebo for six months

Placebo

Participants with SSADH Deficiency receiving SGS-742 when on study drug for six months

SGS-742
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: percentage of stimulator output
-2  (7.1) -0.5  (6.8)
3.Secondary Outcome
Title Change From Baseline of TMS Measurement of Intracortical Facilitation at the End of the Study Drug and Placebo Treatment Periods
Hide Description Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons. Intracortical facilitation (ICF) and inhibition (ICI) were studied using a paired stimulus paradigm. The motor threshold (MT) was first established. The conditioning stimulus (70% MT) followed by the test stimulus (120% MT) was delivered at an interstimulus interval (ISI) of 10 ms for ICF. Each run consisted of 10 trials, and the amplitude ratio of the mean conditioned Motor Evoked Potential (MEP) to control MEP was determined. A larger amplitude ratio indicates greater cortical excitability. The differences between Placebo and Baseline, and SGS and Baseline were obtained. These values were averaged across individuals to report a mean.
Time Frame Baseline and Six months
Hide Outcome Measure Data
Hide Analysis Population Description
We were unable to obtain Motor Thresholds for all participants at all three timepoints, resulting in different N for each time period. All available data is reported.
Arm/Group Title Placebo Study Drug
Hide Arm/Group Description:

Participants with SSADH Deficiency when on placebo for six months

Placebo

Participants with SSADH Deficiency receiving SGS-742 when on study drug for six months

SGS-742
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: ratio of MEP amplitude
49.9  (61.9) 40.5  (50.2)
4.Secondary Outcome
Title Change From Baseline of TMS Measurement of Short Interval Intracortical Inhibition (Short ICI) at the End of the Study Drug and Placebo Treatment Periods
Hide Description Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons. Intracortical facilitation and inhibition were studied using a paired stimulus paradigm. The motor threshold (MT) was first established. The conditioning stimulus (70% MT) followed by the test stimulus (120% MT) was delivered at an interstimulus interval (ISI) of 2 ms for short ICI. Each run consisted of 10 trials, and the amplitude ratio of the mean conditioned Motor Evoked Potential (MEP) to control MEP was determined. A larger amplitude ratio indicates greater cortical excitability. The differences between Placebo and Baseline, and SGS and Baseline were obtained. These values were averaged across individuals to report a mean.
Time Frame Baseline and Six months
Hide Outcome Measure Data
Hide Analysis Population Description
We were unable to obtain Motor Thresholds for all participants at all three timepoints, resulting in different N for each time period. All available data is reported.
Arm/Group Title Placebo Study Drug
Hide Arm/Group Description:

Participants with SSADH Deficiency when on placebo for six months

Placebo

Participants with SSADH Deficiency receiving SGS-742 when on study drug for six months

SGS-742
Overall Number of Participants Analyzed 16 17
Mean (Standard Deviation)
Unit of Measure: ratio of MEP amplitude
35.5  (123.4) -11.0  (54.8)
5.Secondary Outcome
Title Change From Baseline of TMS Measurement of Long Interval Intracortical Inhibition (Long ICI) at the End of the Study Drug and Placebo Treatment Periods
Hide Description Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons.Intracortical facilitation and inhibition were studied using a paired stimulus paradigm. The motor threshold (MT) was first established. The conditioning stimulus (70% MT) followed by the test stimulus (120% MT) was delivered at 100 ms for long ICI. Each run consisted of 10 trials, and the amplitude ratio of the mean conditioned Motor Evoked Potential (MEP) to control MEP was determined. A larger amplitude ratio indicates greater cortical excitability. The differences between Placebo and Baseline, and SGS and Baseline were obtained. These values were averaged across individuals to report a mean.
Time Frame Baseline and Six months
Hide Outcome Measure Data
Hide Analysis Population Description
We were unable to obtain Motor Thresholds for all participants at all three timepoints, resulting in different N for each time period. All available data is reported.
Arm/Group Title Placebo Study Drug
Hide Arm/Group Description:

Participants with SSADH Deficiency when on placebo for six months

Placebo

Participants with SSADH Deficiency receiving SGS-742 when on study drug for six months

SGS-742
Overall Number of Participants Analyzed 15 17
Mean (Standard Deviation)
Unit of Measure: ratio of MEP amplitude
-9.3  (112.0) 0.3  (98.6)
6.Secondary Outcome
Title Results of Physical Examination at the End of the Study Drug and Placebo Treatment Periods
Hide Description A physical examination was administered by a physician to subjects at the end of each six month treatment period, i.e., following completion of a six month period on SGS-742 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0=No observation; 1=Stable baseline findings; 2=New asymptomatic finding; 3=Patient reports some worsening of a baseline daily function associated with new finding; 4=Patient unable to carry out a baseline daily function associated with new finding
Time Frame Six months
Hide Outcome Measure Data
Hide Analysis Population Description
One subject withdrew prior to end of Phase 1
Arm/Group Title Placebo Study Drug
Hide Arm/Group Description:

Participants with SSADH Deficiency when on placebo for six months

Placebo

Participants with SSADH Deficiency receiving SGS-742 when on study drug for six months

SGS-742
Overall Number of Participants Analyzed 18 18
Measure Type: Count of Participants
Unit of Measure: Participants
0
0
   0.0%
0
   0.0%
1
14
  77.8%
15
  83.3%
2
4
  22.2%
3
  16.7%
3
0
   0.0%
0
   0.0%
4
0
   0.0%
0
   0.0%
Time Frame Adverse events were collected over a 16-21 month time period which included a 6 month +/- 2 week Phase 1 period, a 9 week +/- 2 week Washout period, a 6 month +/- 2 week Phase 2 period, followed by a 9 week +/- Washout period.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Washout Period Following Placebo Study Drug Washout Period Following Study Drug
Hide Arm/Group Description

Participants with SSADH Deficiency while on placebo for six months

Placebo

 Participants with SSADH Deficiency having received Placebo, during the 9 week washout period

Participants with SSADH Deficiency receiving SGS-742 while on study drug for six months

SGS-742

 Participants with SSADH Deficiency having received SGS-742, during the 9 week washout period
All-Cause Mortality
Placebo Washout Period Following Placebo Study Drug Washout Period Following Study Drug
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/18 (0.00%)      0/16 (0.00%)      0/19 (0.00%)      0/18 (0.00%)    
Hide Serious Adverse Events
Placebo Washout Period Following Placebo Study Drug Washout Period Following Study Drug
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/18 (0.00%)      0/16 (0.00%)      0/19 (0.00%)      0/18 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Washout Period Following Placebo Study Drug Washout Period Following Study Drug
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/18 (88.89%)      3/16 (18.75%)      18/19 (94.74%)      6/18 (33.33%)    
Ear and labyrinth disorders         
Allergic Rhinitis *  1/18 (5.56%)  2 2/16 (12.50%)  2 2/19 (10.53%)  2 0/18 (0.00%)  0
Ear Pain *  0/18 (0.00%)  0 0/16 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Nasal congestion *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Eye disorders         
Red eyes *  0/18 (0.00%)  0 0/16 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Gastrointestinal disorders         
Abdominal Pain *  2/18 (11.11%)  3 0/16 (0.00%)  0 4/19 (21.05%)  6 1/18 (5.56%)  1
Anorexia *  0/18 (0.00%)  0 0/16 (0.00%)  0 1/19 (5.26%)  2 1/18 (5.56%)  1
Blister in the oral cavity *  0/18 (0.00%)  0 0/16 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Bloating *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Diarrhea *  2/18 (11.11%)  2 0/16 (0.00%)  0 2/19 (10.53%)  2 1/18 (5.56%)  1
Dry Mouth *  1/18 (5.56%)  1 0/16 (0.00%)  0 1/19 (5.26%)  2 0/18 (0.00%)  0
Increased appetite *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Nausea *  5/18 (27.78%)  5 0/16 (0.00%)  0 2/19 (10.53%)  3 0/18 (0.00%)  0
Vomiting *  4/18 (22.22%)  4 1/16 (6.25%)  1 2/19 (10.53%)  3 0/18 (0.00%)  0
General disorders         
Fatigue *  5/18 (27.78%)  5 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Fever *  2/18 (11.11%)  2 0/16 (0.00%)  0 3/19 (15.79%)  4 1/18 (5.56%)  1
Infections and infestations         
Head lice *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Labile *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Pharyngitis *  1/18 (5.56%)  1 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Rash *  1/18 (5.56%)  1 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Strep throat *  0/18 (0.00%)  0 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Urinary Tract Infection *  1/18 (5.56%)  2 1/16 (6.25%)  1 2/19 (10.53%)  3 0/18 (0.00%)  0
Vaginal infection *  0/18 (0.00%)  0 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Injury, poisoning and procedural complications         
Bruising *  1/18 (5.56%)  2 0/16 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Investigations         
Weight gain *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Metabolism and nutrition disorders         
Anorexia *  0/18 (0.00%)  0 0/16 (0.00%)  0 2/19 (10.53%)  2 0/18 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back pain *  0/18 (0.00%)  0 0/16 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Muscle weakness upper limb *  0/18 (0.00%)  0 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Nervous system disorders         
Concentration Impairment *  0/18 (0.00%)  0 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Dizziness *  2/18 (11.11%)  2 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Headache *  1/18 (5.56%)  1 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Hyperactivity *  1/18 (5.56%)  1 0/16 (0.00%)  0 2/19 (10.53%)  2 0/18 (0.00%)  0
Insomnia *  1/18 (5.56%)  1 0/16 (0.00%)  0 1/19 (5.26%)  2 0/18 (0.00%)  0
Lethargy *  3/18 (16.67%)  3 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Seizures *  1/18 (5.56%)  1 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Sleepiness *  2/18 (11.11%)  2 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Syncope *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Psychiatric disorders         
Agitation *  1/18 (5.56%)  1 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Anxiety *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Irritability *  2/18 (11.11%)  5 0/16 (0.00%)  0 3/19 (15.79%)  3 2/18 (11.11%)  2
Labile *  0/18 (0.00%)  0 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Renal and urinary disorders         
Abnormal Urinary Analysis results *  0/18 (0.00%)  0 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Priapism *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Cough *  1/18 (5.56%)  2 1/16 (6.25%)  1 0/19 (0.00%)  0 0/18 (0.00%)  0
Nasal congestion *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Upper Respiratory Infection *  2/18 (11.11%)  2 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
Skin and subcutaneous tissue disorders         
Acne *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Alopecia *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Blister *  0/18 (0.00%)  0 0/16 (0.00%)  0 0/19 (0.00%)  0 1/18 (5.56%)  1
Rash *  2/18 (11.11%)  2 0/16 (0.00%)  0 4/19 (21.05%)  4 1/18 (5.56%)  1
Urticaria *  1/18 (5.56%)  1 0/16 (0.00%)  0 0/19 (0.00%)  0 0/18 (0.00%)  0
Vascular disorders         
Flushing *  0/18 (0.00%)  0 0/16 (0.00%)  0 1/19 (5.26%)  1 0/18 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. William Theodore
Organization: National Institutes of Health
Phone: 301-496-1505
EMail: theodorw@ninds.nih.gov
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT02019667    
Other Study ID Numbers: 140033
14-N-0033 ( Other Identifier: NIH )
First Submitted: December 20, 2013
First Posted: December 24, 2013
Results First Submitted: November 21, 2019
Results First Posted: February 24, 2020
Last Update Posted: February 24, 2020