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    Clinical Trial Results:
    A Phase 2, Multicenter, Multinational, Open-Label, Dose-Escalation Study to Evaluate the Safety and Efficacy of ORGN001 (formerly ALXN1101) in Pediatric Patients with Molybdenum Cofactor Deficiency (MoCD) Type A Currently Treated with Recombinant Escherichia Coli-Derived Cyclic Pyranopterin Monophosphate (rcPMP)

    Summary
    EudraCT number
    		 2013-002701-56
    Trial protocol
    		 GB   NL  
    Global end of trial date
    15 Aug 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 Sep 2023
    First version publication date
    17 Sep 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ALXN1101-MCD-201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02047461
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Origin Biosciences (affiliate of BridgeBio)
    Sponsor organisation address
    Suite 250, 3160 Porter Drive, Palo Alto, CA, United States, 94304
    Public contact
    Business Development and Operations, Origin Biosciences (affiliate of BridgeBio), +1 650-391-9740,
    Scientific contact
    Business Development and Operations, Origin Biosciences (affiliate of BridgeBio), +1 650-391-9740,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001491-PIP01-13
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    24 May 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Aug 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Aug 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this clinical study was to evaluate the safety of fosdenopterin over the first 6 months of treatment.
    Protection of trial subjects
    The study was conducted in accordance with Good Clinical Practice (GCP) and the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 A placebo-controlled study would not have been appropriate due to the severity of the untreated disease and the reported improved outcomes of newborn infants with MoCD Type A who were treated with rcPMP. An active comparator study was not feasible due to the lack of an approved treatment for MoCD Type A.
    Actual start date of recruitment
    01 Feb 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 72 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Tunisia: 1
    Country: Number of subjects enrolled
    United States: 1
    Worldwide total number of subjects
    8
    EEA total number of subjects
    2
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    2
    Children (2-11 years)
    6
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 8 subjects were enrolled and analyzed. The subjects were recruited from Australia, Tunisia, the Netherlands, United Kingdom, and USA.

    Pre-assignment
    Screening details
    		 Subject screening evaluations were performed at any time during the screening period (Days -21 to -1) before the 1st dose of fosdenopterin. Enrolled patients attended at least 2 study visits for baseline data collection. Subjects continued to receive daily IV infusions of their current rcPMP treatment during the screening period.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    N/A

    Arms
    Arm title
    		 Subjects Receiving rcPMP and transitioned to ORGN001
    Arm description
    		 Patients currently receiving rcPMP infusions at baseline are transitioned to ORGN001(formerly ALXN1101), starting at their current rcPMP dose and escalating to a target dose of 0.9 mg/kg per protocol
    Arm type
    		 Experimental

    Investigational medicinal product name
    Fosdenopterin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Infusion
    Dosage and administration details
    Fosdenopterin (2.5 mg/vial and 12.5 mg/vial), Dose level: same as current dose of rcPMP, IV infusion, approximately 24 (+-3) hours after the last rcPMP treatment, daily. After 2 months of treatment, Fosdenopterin (2.5 mg/vial and 12.5 mg/vial), Dose level: escalation each month as per protocol (but no more than 240 μg/kg/Day), IV infusion, daily.

    Number of subjects in period 1
    		Subjects Receiving rcPMP and transitioned to ORGN001
    Started
    8
    Completed
    8

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    		 -

    Reporting group values
    		 Overall Study Total
    Number of subjects
    		 8 8
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 2 2
        Children (2-11 years)
    		 6 6
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 0 0
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    		 45.2 ( 22.96 ) -
    Gender categorical
    Units: Subjects
        Female
    		 5 5
        Male
    		 3 3
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 0
        Not Hispanic or Latino
    		 8 8
        Not Reported
    		 0 0
        Missing/Unknown
    		 0 0
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0
        Asian
    		 3 3
        Black or African American
    		 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0
        White
    		 5 5
        Other
    		 0 0
        Missing/Unknown
    		 0 0

    End points

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    End points reporting groups
    Reporting group title
    Subjects Receiving rcPMP and transitioned to ORGN001
    Reporting group description
    		 Patients currently receiving rcPMP infusions at baseline are transitioned to ORGN001(formerly ALXN1101), starting at their current rcPMP dose and escalating to a target dose of 0.9 mg/kg per protocol

    Primary: Safety of ORGN001 (Formerly ALXN1101)

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    End point title
    		 Safety of ORGN001 (Formerly ALXN1101) [1]
    End point description
    Treatment Emergent Serious Adverse Events
    End point type
    Primary
    End point timeframe
    Baseline to Study Completion (full study duration)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal statistical hypothesis testing will be performed. Efficacy data will be analyzed using descriptive statistics. All data collected during the study will be presented in summary tables, figures, or by-subject data listings. Continuous variables will be summarized using mean, SD, median, minimum, and maximum. Categorical variables will be summarized using percentages and frequency distributions. Graphical displays will be produced as appropriate.
    End point values
    		 Subjects Receiving rcPMP and transitioned to ORGN001
    Number of subjects analysed
    8
    Units: number of subjects affected
        Gastrointestinal disorders
    1
        General disorders and administration site conditio
    5
        Infections and infestations
    6
        Injury, poisoning and procedural complications
    2
        Metabolism and nutrition disorders
    2
        Musculoskeletal and connective tissue disorders
    1
        Nervous system disorders
    2
        Product issues
    2
        Respiratory, thoracic and mediastinal disorders
    2
        Skin and subcutaneous tissue disorders
    1
        Surgical and medical procedures
    1
        Vascular disorders
    2
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (Actual Plasma Concentration) of ORGN001 (Formerly ALXN1101)

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    End point title
    		 Pharmacokinetics (Actual Plasma Concentration) of ORGN001 (Formerly ALXN1101)
    End point description
    ORGN001 levels by dose at pre-infusion and end of infusion (EOI) atscheduled timepoints. Measurement is actual plasma concentration of ORGN001 at measured timepoints,starting at their current rcPMP dose. 6 subjects started at a dose of 240 mcg/kg, 1 subject at 248 mcg/kg, and 1 subject at 280 mcg/kg. (EOI = End of Infusion). 1 subject is missing a pre-infusion dose measurement.
    End point type
    Secondary
    End point timeframe
    First 6 months at each dose level, where available
    End point values
    		 Subjects Receiving rcPMP and transitioned to ORGN001
    Number of subjects analysed
    8 [2]
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 1 Pre-infusion(240mcg/kg) (6 subjects)
    3.95 ( 9.68 )
        Day 1 Pre-infusion(248mcg/kg) (1 subjects)
    0 ( 0 )
        Day 1 EOI(240mcg/kg) (6 subjects)
    669.00 ( 236.06 )
        Day 1 EOI(248mcg/kg) (1 subject)
    980.00 ( 0.00 )
        Day 1 EOI(280mcg/kg) (1 subject)
    770.00 ( 0.00 )
        Day 7 EOI(240mcg/kg) (6 subjects)
    669.50 ( 246.72 )
        Day 7 EOI(248mcg/kg) (1 subject)
    694.00 ( 0.00 )
        Day 7 EOI(280mcg/kg) (1 subject)
    938.00 ( 0.00 )
        Day 60 EOI(480mcg/kg) (5 subjects)
    880.84 ( 558.56 )
        Day 90 EOI(240mcg/kg) (1 subject)
    1230.00 ( 0.00 )
        Day 90 EOI(480mcg/kg) (1 subject)
    762.00 ( 0.00 )
        Day 90 EOI(720mcg/kg) (6 subjects)
    1888.33 ( 271.10 )
        Day 120EOI (480mcg/kg) (1 subject)
    2810.00 ( 0.00 )
        Day 120EOI (720mcg/kg) (1 subject)
    671.00 ( 0.00 )
        Day 120EOI (960mcg/kg) (6 subjects)
    4213.33 ( 4520.31 )
        Day 150EOI (720mcg/kg) (1 subject)
    3810.00 ( 0.00 )
        Day 150EOI (960mcg/kg) (3 subjects)
    2045.67 ( 1009.85 )
        Day 150EOI (1200mcg/kg) (3 subjects)
    3173.33 ( 656.53 )
        Month 66 EOI (1200mcg/kg) (2 subjects)
    2450.00 ( 381.84 )
    Notes
    [2] - For some [C] there is only 1 patient with data, thus no SD. For each [C], no of subjects differ.
    No statistical analyses for this end point

    Secondary: S-sulfocysteine (Umol/L) Normalized to Urine Creatinine (mmol/L) -Change From Baseline Over Time

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    End point title
    		 S-sulfocysteine (Umol/L) Normalized to Urine Creatinine (mmol/L) -Change From Baseline Over Time
    End point description
    Analyses were performed on urine SSC, a biomarker of the MoCD pathway. Levels of SSC measured in urine were normalized to urine creatinine levels. The observed value, change, and percent change in urine and blood SSC levels from baseline were summarized by visit overtime. Not all subjects had samples taken at each expected timepoint.
    End point type
    Secondary
    End point timeframe
    Until study completion (approx. 72 months)
    End point values
    		 Subjects Receiving rcPMP and transitioned to ORGN001
    Number of subjects analysed
    8 [3]
    Units: umol/mmol
    arithmetic mean (standard deviation)
        Baseline (8 subjects)
    21.1 ( 12.89 )
        Day 4 Change from Baseline (8 subjects)
    -1.7 ( 12.70 )
        Day 7 Change from Baseline (8 subjects)
    -7.8 ( 9.70 )
        Day 14 Change from Baseline (8 subjects)
    -2.2 ( 14.51 )
        Day 28 Change from Baseline (7 subjects)
    2.8 ( 14.17 )
        Day 57 Change from Baseline (7 subjects)
    -3.0 ( 10.29 )
        Day 67 Change from Baseline (5 subjects)
    -5.7 ( 11.78 )
        Day 87 Change from Baseline (6 subjects)
    -9.6 ( 11.70 )
        Day 97 Change from Baseline (6 subjects)
    -9.0 ( 11.12 )
        Day 117 Change from Baseline (7 subjects)
    -12.8 ( 15.58 )
        Day 127 Change from Baseline (8 subjects)
    -12.2 ( 14.77 )
        Day 147 Change from Baseline (8 subjects)
    -13.7 ( 11.86 )
        Day 157 Change from Baseline (5 subjects)
    -14.3 ( 16.87 )
        Month 6 Change from Baseline (8 subjects)
    -13.6 ( 11.77 )
        Month 9 Change from Baseline (8 subjects)
    -8.7 ( 17.14 )
        Month 12 Change from Baseline (8 subjects)
    -8.6 ( 20.15 )
        Month 18 Change from Baseline (6 subjects)
    -11.4 ( 16.81 )
        Month 24 Change from Baseline (6 subjects)
    -14.3 ( 14.73 )
        Month 30 Change from Baseline (5 subjects)
    -11.2 ( 21.28 )
        Month 36 Change from Baseline (5 subjects)
    -13.2 ( 18.40 )
        Month 48 Change from Baseline (5 subjects)
    -6.7 ( 6.65 )
        Month 60 Change from Baseline (4 subjects)
    -17.9 ( 14.59 )
        Month 78 Change from Baseline (4 subjects)
    -15.6 ( 11.82 )
        Month 84 Change from Baseline (1 subject)
    -5.3 ( 0.00 )
        Month 90 Change from Baseline (2 subjects)
    1.7 ( 10.25 )
    Notes
    [3] - For some [C] there is only 1 patient with data, thus no SD. For each [C], no of subjects diffe
    No statistical analyses for this end point

    Secondary: Effect of ORGN001 on Neurologic Function Including Motor Examination

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    End point title
    		 Effect of ORGN001 on Neurologic Function Including Motor Examination
    End point description
    Change from baseline on repeated Neurologic examinations such as muscle strength and tone, as well as sensory and reflex exam. All subjects entering the study had complete examinations throughout the study to identify Normal vs Abnormal Neurologic Function on the parameters presented. Data shown here are from Baseline up to M30. For data from M36 to M90 (final examination), please refer to section 14 of CSR.
    End point type
    Secondary
    End point timeframe
    Until study completion (approx. 72 months)
    End point values
    		 Subjects Receiving rcPMP and transitioned to ORGN001
    Number of subjects analysed
    8 [4]
    Units: subjects
        Quality of Spontaneous Movement at Baseline (N)
    3
        Quality of Spontaneous Movement at Baseline (A)
    5
        Quality of Spontaneous Movement at D1 (N)
    4
        Quality of Spontaneous Movement at D1 (A)
    4
        Quality of Spontaneous Movement at D4 (N)
    3
        Quality of Spontaneous Movement at D4 (A)
    5
        Quality of Spontaneous Movement at D7 (N)
    3
        Quality of Spontaneous Movement at D7 (A)
    4
        Quality of Spontaneous Movement at D14 (N)
    2
        Quality of Spontaneous Movement at D14 (A)
    5
        Quality of Spontaneous Movement at D28 (N)
    3
        Quality of Spontaneous Movement at D28 (A)
    4
        Quality of Spontaneous Movement at D60 (N)
    2
        Quality of Spontaneous Movement at D60 (A)
    4
        Quality of Spontaneous Movement at D90 (N)
    4
        Quality of Spontaneous Movement at D90 (A)
    4
        Quality of Spontaneous Movement at D120 (N)
    2
        Quality of Spontaneous Movement at D120 (A)
    6
        Quality of Spontaneous Movement at D150 (N)
    4
        Quality of Spontaneous Movement at D150 (A)
    4
        Quality of Spontaneous Movement at D180 (N)
    3
        Quality of Spontaneous Movement at D180 (A)
    5
        Quality of Spontaneous Movement at M9 (N)
    3
        Quality of Spontaneous Movement at M9 (A)
    5
        Quality of Spontaneous Movement at M12 (N)
    3
        Quality of Spontaneous Movement at M12 (A)
    5
        Quality of Spontaneous Movement at M18 (N)
    4
        Quality of Spontaneous Movement at M18 (A)
    4
        Quality of Spontaneous Movement at M24 (N)
    2
        Quality of Spontaneous Movement at M24 (A)
    6
        Quality of Spontaneous Movement at M30 (N)
    4
        Quality of Spontaneous Movement at M30 (A)
    4
        Dystonic at Baseline (N)
    4
        Dystonic at Baseline (A)
    4
        Dystonic at D1 (N)
    4
        Dystonic at D1 (A)
    4
        Dystonic at D4 (N)
    5
        Dystonic at D4 (A)
    3
        Dystonic at D7 (N)
    4
        Dystonic at D7 (A)
    3
        Dystonic at D14 (N)
    4
        Dystonic at D14 (A)
    3
        Dystonic at D28 (N)
    4
        Dystonic at D28 (A)
    3
        Dystonic at D60 (N)
    4
        Dystonic at D60 (A)
    2
        Dystonic at D90 (N)
    4
        Dystonic at D90 (A)
    4
        Dystonic at D120 (N)
    4
        Dystonic at D120 (A)
    4
        Dystonic at D150 (N)
    4
        Dystonic at D150 (A)
    4
        Dystonic at D180 (N)
    4
        Dystonic at D180 (A)
    4
        Dystonic at M9 (N)
    4
        Dystonic at M9 (A)
    4
        Dystonic at M12 (N)
    4
        Dystonic at M12 (A)
    4
        Dystonic at M18 (N)
    3
        Dystonic at M18 (A)
    5
        Dystonic at M24 (N)
    4
        Dystonic at M24 (A)
    4
        Dystonic at M30 (N)
    4
        Dystonic at M30 (A)
    4
        Opistonic at Baseline (N)
    7
        Opistonic at Baseline (A)
    1
        Opistonic at D1 (N)
    7
        Opistonic at D1 (A)
    1
        Opistonic at D4 (N)
    8
        Opistonic at D4 (A)
    0
        Opistonic at D7 (N)
    7
        Opistonic at D7 (A)
    0
        Opistonic at D14 (N)
    7
        Opistonic at D14 (A)
    0
        Opistonic at D28 (N)
    7
        Opistonic at D28 (A)
    0
        Opistonic at D60 (N)
    6
        Opistonic at D60 (A)
    0
        Opistonic at D90 (N)
    8
        Opistonic at D90 (A)
    0
        Opistonic at D120 (N)
    7
        Opistonic at D120 (A)
    1
        Opistonic at D150 (N)
    8
        Opistonic at D150 (A)
    0
        Opistonic at D180 (N)
    8
        Opistonic at D180 (A)
    0
        Opistonic at M9 (N)
    7
        Opistonic at M9 (A)
    1
        Opistonic at M12 (N)
    7
        Opistonic at M12 (A)
    1
        Opistonic at M18 (N)
    6
        Opistonic at M18 (A)
    2
        Opistonic at M24 (N)
    6
        Opistonic at M24 (A)
    2
        Opistonic at M30 (N)
    6
        Opistonic at M30 (A)
    2
        Truncal Tone at Baseline (N)
    2
        Truncal Tone at Baseline (A)
    5
        Truncal Tone at D1 (N)
    3
        Truncal Tone at D1 (A)
    5
        Truncal Tone at D4 (N)
    2
        Truncal Tone at D4 (A)
    5
        Truncal Tone at D7 (N)
    2
        Truncal Tone at D7 (A)
    5
        Truncal Tone at D14 (N)
    2
        Truncal Tone at D14 (A)
    5
        Truncal Tone at D28 (N)
    3
        Truncal Tone at D28 (A)
    4
        Truncal Tone at D60 (N)
    3
        Truncal Tone at D60 (A)
    3
        Truncal Tone at D90 (N)
    3
        Truncal Tone at D90 (A)
    5
        Truncal Tone at D120 (N)
    3
        Truncal Tone at D120 (A)
    5
        Truncal Tone at D150 (N)
    2
        Truncal Tone at D150 (A)
    6
        Truncal Tone at D180 (N)
    2
        Truncal Tone at D180 (A)
    6
        Truncal Tone at M9 (N)
    2
        Truncal Tone at M9 (A)
    6
        Truncal Tone at M12 (N)
    3
        Truncal Tone at M12 (A)
    5
        Truncal Tone at M18 (N)
    3
        Truncal Tone at M18 (A)
    5
        Truncal Tone at M24 (N)
    2
        Truncal Tone at M24 (A)
    6
        Truncal Tone at M30 (N)
    2
        Truncal Tone at M30 (A)
    6
        Appendicular Tone at Baseline (N)
    2
        Appendicular Tone at Baseline (A)
    6
        Appendicular Tone at D1 (N)
    2
        Appendicular Tone at D1 (A)
    6
        Appendicular Tone at D4 (N)
    2
        Appendicular Tone at D4 (A)
    6
        Appendicular Tone at D7 (N)
    2
        Appendicular Tone at D7 (A)
    5
        Appendicular Tone at D14 (N)
    1
        Appendicular Tone at D14 (A)
    6
        Appendicular Tone at D28 (N)
    2
        Appendicular Tone at D28 (A)
    5
        Appendicular Tone at D60 (N)
    1
        Appendicular Tone at D60 (A)
    5
        Appendicular Tone at D90 (N)
    2
        Appendicular Tone at D90 (A)
    6
        Appendicular Tone at D120 (N)
    1
        Appendicular Tone at D120 (A)
    7
        Appendicular Tone at D150 (N)
    1
        Appendicular Tone at D150 (A)
    7
        Appendicular Tone at D180 (N)
    2
        Appendicular Tone at D180 (A)
    6
        Appendicular Tone at M9 (N)
    1
        Appendicular Tone at M9 (A)
    7
        Appendicular Tone at M12 (N)
    2
        Appendicular Tone at M12 (A)
    6
        Appendicular Tone at M18 (N)
    1
        Appendicular Tone at M18 (A)
    7
        Appendicular Tone at M24 (N)
    1
        Appendicular Tone at M24 (A)
    7
        Appendicular Tone at M30 (N)
    1
        Appendicular Tone at M30 (A)
    7
        Deep Tendon Reflexes at Baseline (N)
    4
        Deep Tendon Reflexes at Baseline (A)
    4
        Deep Tendon Reflexes at D1 (N)
    3
        Deep Tendon Reflexes at D1 (A)
    5
        Deep Tendon Reflexes at D4 (N)
    1
        Deep Tendon Reflexes at D4 (A)
    6
        Deep Tendon Reflexes at D7 (N)
    2
        Deep Tendon Reflexes at D7 (A)
    5
        Deep Tendon Reflexes at D14 (N)
    2
        Deep Tendon Reflexes at D14 (A)
    5
        Deep Tendon Reflexes at D28 (N)
    3
        Deep Tendon Reflexes at D28 (A)
    4
        Deep Tendon Reflexes at D60 (N)
    2
        Deep Tendon Reflexes at D60 (A)
    4
        Deep Tendon Reflexes at D90 (N)
    3
        Deep Tendon Reflexes at D90 (A)
    5
        Deep Tendon Reflexes at D120 (N)
    2
        Deep Tendon Reflexes at D120 (A)
    6
        Deep Tendon Reflexes at D150 (N)
    3
        Deep Tendon Reflexes at D150 (A)
    5
        Deep Tendon Reflexes at D180 (N)
    4
        Deep Tendon Reflexes at D180 (A)
    4
        Deep Tendon Reflexes at M9 (N)
    4
        Deep Tendon Reflexes at M9 (A)
    4
        Deep Tendon Reflexes at M12 (N)
    3
        Deep Tendon Reflexes at M12 (A)
    5
        Deep Tendon Reflexes at M18 (N)
    2
        Deep Tendon Reflexes at M18 (A)
    6
        Deep Tendon Reflexes at M24 (N)
    2
        Deep Tendon Reflexes at M24 (A)
    6
        Deep Tendon Reflexes at M30 (N)
    3
        Deep Tendon Reflexes at M30 (A)
    5
        Primitive Reflexes at Baseline (N)
    5
        Primitive Reflexes at Baseline (A)
    1
        Primitive Reflexes at D1 (N)
    4
        Primitive Reflexes at D1 (A)
    1
        Primitive Reflexes at D4 (N)
    5
        Primitive Reflexes at D4 (A)
    1
        Primitive Reflexes at D7 (N)
    3
        Primitive Reflexes at D7 (A)
    2
        Primitive Reflexes at D14 (N)
    2
        Primitive Reflexes at D14 (A)
    1
        Primitive Reflexes at D28 (N)
    3
        Primitive Reflexes at D28 (A)
    1
        Primitive Reflexes at D60 (N)
    3
        Primitive Reflexes at D60 (A)
    1
        Primitive Reflexes at D90 (N)
    4
        Primitive Reflexes at D90 (A)
    1
        Primitive Reflexes at D120 (N)
    4
        Primitive Reflexes at D120 (A)
    0
        Primitive Reflexes at D150 (N)
    5
        Primitive Reflexes at D150 (A)
    0
        Primitive Reflexes at D180 (N)
    5
        Primitive Reflexes at D180 (A)
    1
        Primitive Reflexes at M9 (N)
    4
        Primitive Reflexes at M9 (A)
    2
        Primitive Reflexes at M12 (N)
    5
        Primitive Reflexes at M12 (A)
    1
        Primitive Reflexes at M18 (N)
    6
        Primitive Reflexes at M18 (A)
    1
        Primitive Reflexes at M24 (N)
    6
        Primitive Reflexes at M24 (A)
    1
        Primitive Reflexes at M30 (N)
    6
        Primitive Reflexes at M30 (A)
    1
        Clonus presence at Baseline (N)
    7
        Clonus presence at Baseline (A)
    1
        Clonus presence at D1 (N)
    7
        Clonus presence at D1 (A)
    1
        Clonus presence at D4 (N)
    7
        Clonus presence at D4 (A)
    1
        Clonus presence at D7 (N)
    6
        Clonus presence at D7 (A)
    2
        Clonus presence at D14 (N)
    6
        Clonus presence at D14 (A)
    1
        Clonus presence at D28 (N)
    5
        Clonus presence at D28 (A)
    2
        Clonus presence at D60 (N)
    5
        Clonus presence at D60 (A)
    1
        Clonus presence at D90 (N)
    6
        Clonus presence at D90 (A)
    1
        Clonus presence at D120 (N)
    7
        Clonus presence at D120 (A)
    1
        Clonus presence at D150 (N)
    6
        Clonus presence at D150 (A)
    2
        Clonus presence at D180 (N)
    6
        Clonus presence at D180 (A)
    2
        Clonus presence at M9 (N)
    8
        Clonus presence at M9 (A)
    0
        Clonus presence at M12 (N)
    7
        Clonus presence at M12 (A)
    1
        Clonus presence at M18 (N)
    6
        Clonus presence at M18 (A)
    2
        Clonus presence at M24 (N)
    6
        Clonus presence at M24 (A)
    2
        Clonus presence at M30 (N)
    6
        Clonus presence at M30 (A)
    2
        Ambulation at Baseline (N)
    4
        Ambulation at Baseline (A)
    4
        Ambulation at D1 (N)
    4
        Ambulation at D1 (A)
    4
        Ambulation at D4 (N)
    4
        Ambulation at D4 (A)
    4
        Ambulation at D7 (N)
    3
        Ambulation at D7 (A)
    4
        Ambulation at D14 (N)
    3
        Ambulation at D14 (A)
    4
        Ambulation at D28 (N)
    3
        Ambulation at D28 (A)
    4
        Ambulation at D60 (N)
    3
        Ambulation at D60 (A)
    3
        Ambulation at D90 (N)
    4
        Ambulation at D90 (A)
    4
        Ambulation at D120 (N)
    4
        Ambulation at D120 (A)
    4
        Ambulation at D150 (N)
    4
        Ambulation at D150 (A)
    4
        Ambulation at D180 (N)
    4
        Ambulation at D180 (A)
    4
        Ambulation at M9 (N)
    4
        Ambulation at M9 (A)
    4
        Ambulation at M12 (N)
    4
        Ambulation at M12 (A)
    4
        Ambulation at M18 (N)
    4
        Ambulation at M18 (A)
    4
        Ambulation at M24 (N)
    4
        Ambulation at M24 (A)
    4
        Ambulation at M30 (N)
    4
        Ambulation at M30 (A)
    4
        Communication at Baseline (N)
    1
        Communication at Baseline (A)
    7
        Communication at D1 (N)
    1
        Communication at D1 (A)
    7
        Communication at D4 (N)
    1
        Communication at D4 (A)
    7
        Communication at D7 (N)
    1
        Communication at D7 (A)
    6
        Communication at D14 (N)
    0
        Communication at D14 (A)
    7
        Communication at D28 (N)
    2
        Communication at D28 (A)
    5
        Communication at D60 (N)
    2
        Communication at D60 (A)
    4
        Communication at D90 (N)
    1
        Communication at D90 (A)
    7
        Communication at D120 (N)
    1
        Communication at D120 (A)
    7
        Communication at D150 (N)
    2
        Communication at D150 (A)
    6
        Communication at D180 (N)
    2
        Communication at D180 (A)
    6
        Communication at M9 (N)
    2
        Communication at M9 (A)
    6
        Communication at M12 (N)
    2
        Communication at M12 (A)
    6
        Communication at M18 (N)
    2
        Communication at M18 (A)
    6
        Communication at M24 (N)
    2
        Communication at M24 (A)
    6
        Communication at M30 (N)
    2
        Communication at M30 (A)
    6
    Notes
    [4] - For D7, 14, 28 -> N=7. For D60, N=6. (N): Normal/Present/Yes. (A): Abnormal/Absent/No,
    No statistical analyses for this end point

    Secondary: Long-term Safety of ORGN001

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    End point title
    		 Long-term Safety of ORGN001
    End point description
    Change from baseline in Seizure frequency Number of subjects with Seizures in observation period
    End point type
    Secondary
    End point timeframe
    Until study completion (approx. 72 months)
    End point values
    		 Subjects Receiving rcPMP and transitioned to ORGN001
    Number of subjects analysed
    8 [5]
    Units: subjects
        Screening (N=7)
    3
        Baseline to Month 6 (N=7)
    4
        Month 6 to Month 12 (N=8)
    3
        Month 12 to Month 18 (N=8)
    3
        Month 18 to Month 24 (N=8)
    3
        Month 24 to Month 30 (N=8)
    3
        Month 30 to Month 36 (N=7)
    3
        Month 36 to Month 42 (N=7)
    3
        Month 42 to Month 48 (N=7)
    3
        Month 48 to Month 54 (N=7)
    3
        Month 54 to Month 60 (N=7)
    3
        Month 60 to Month 66 (N=7)
    3
        Month 66 to Month 72 (N=7)
    3
        Month 72 to Month 78 (N=7)
    3
        Month 78 to Month 84 (N=6)
    2
        Month 84 to Month 90 (N=6)
    2
        Month 90 to Month 96 (N=3)
    2
    Notes
    [5] - For each timepoint, the number of analyzed subjects differ.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse event data were collected from Day 1 with ORGN001 treatment until study completion, up to Month 90.
    Adverse event reporting additional description
    All-cause Mortality is zero in this study because there were no deaths that occurred. SAE Data presented is for all SAEs that occurred during the whole study in all subjects.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Subjects Receiving rcPMP and transitioned to ORGN001
    Reporting group description
    		 Patients currently receiving rcPMP infusions at baseline are transitioned to ORGN001(formerly ALXN1101), starting at their current rcPMP dose and escalating to a target dose of 0.9 mg/kg per protocol

    Serious adverse events
    		 Subjects Receiving rcPMP and transitioned to ORGN001
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 8 (87.50%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Injury, poisoning and procedural complications
    Postoperative respiratory failure
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Haemorrhage
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Surgical and medical procedures
    Central venous catheterisation
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Dystonia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Complication associated with device
         subjects affected / exposed
    4 / 8 (50.00%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Catheter site irritation
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Swelling
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Catheter site discharge
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Catheter site extravasation
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Erosive oesophagitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonitis aspiration
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper airway obstruction
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin disorder
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Joint contracture
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Catheter site infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Device related infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Vascular device infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Catheter site abscess
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Device leakage
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Subjects Receiving rcPMP and transitioned to ORGN001
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    8 / 8 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Melanocytic naevus
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Pyogenic granuloma
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Vascular disorders
    Haemorrhage
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Venous thrombosis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Phlebitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Cyanosis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    3
    Surgical and medical procedures
    Central venous catheterisation
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    General disorders and administration site conditions
    Catheter site pain
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    4
    Catheter site discharge
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Catheter site discolouration
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Catheter site extravasation
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Catheter site haemorrhage
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Catheter site irritation
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    5
    Catheter site oedema
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Chills
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    3
    Complication associated with device
         subjects affected / exposed
    6 / 8 (75.00%)
         occurrences all number
    16
    Gait disturbance
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Medical device site discomfort
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Medical device site reaction
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    3
    Pain
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Pyrexia
         subjects affected / exposed
    7 / 8 (87.50%)
         occurrences all number
    38
    Swelling
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Swelling face
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Asthma
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    7
    Asthmatic crisis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Bronchopneumopathy
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Cough
         subjects affected / exposed
    4 / 8 (50.00%)
         occurrences all number
    7
    Epistaxis
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Increased upper airway secretion
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Lung disorder
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Obstructive sleep apnoea syndrome
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Oropharyngeal pain
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Pneumonitis aspiration
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Productive cough
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Respiratory failure
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    2
    Rhinitis allergic
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Sneezing
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Tachypnoea
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    3
    Upper airway obstruction
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    3
    Wheezing
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Insomnia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Irritability
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Sleep disorder
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Product issues
    Device dislocation
         subjects affected / exposed
    3 / 8 (37.50%)
         occurrences all number
    6
    Device leakage
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Device occlusion
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Investigations
    Blood iron decreased
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    C-reactive protein increased
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Cardiac murmur
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Culture urine positive
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    2
    Heart rate increased
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Procalcitonin increased
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Vitamin D decreased
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Joint dislocation
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Muscle injury
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Post procedural complication
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Postoperative respiratory failure
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Procedural pain
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Scar
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Tendon injury
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Thermal burn
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Traumatic haematoma
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    2
    Nervous system disorders
    Cerebral atrophy
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Dystonia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    9
    Epilepsy
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Hypertonia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Muscle spasticity
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    2
    Opisthotonus
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Seizure
         subjects affected / exposed
    3 / 8 (37.50%)
         occurrences all number
    8
    Tonic convulsion
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Tremor
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Iron deficiency anaemia
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Leukocytosis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Lymphadenopathy
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Splenomegaly
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    4
    Tympanic membrane hyperaemia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Eye disorders
    Chalazion
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Eye irritation
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Eye pruritus
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Eye swelling
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Strabismus
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Barrett's oesophagus
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Constipation
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    4
    Diarrhoea
         subjects affected / exposed
    3 / 8 (37.50%)
         occurrences all number
    5
    Dysphagia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Erosive oesophagitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Gastritis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    2
    Gastroesophageal reflux disease
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    2
    Gastrointestinal motility disorder
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Mouth haemorrhage
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Nausea
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    3
    Noninfective gingivitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Retching
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Salivary hypersecretion
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    2
    Teething
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Vomiting
         subjects affected / exposed
    6 / 8 (75.00%)
         occurrences all number
    11
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Erythema
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Keratosis pilaris
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Livedo reticularis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Petechiae
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Purpura
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Rash
         subjects affected / exposed
    3 / 8 (37.50%)
         occurrences all number
    3
    Rash erythematous
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Rash maculo-papular
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Rash erythematous bilateral
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Skin disorder
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Seborrhoeic dermatitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Skin ulcer
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Skin irritation
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Urticaria
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Foot deformity
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Growth retardation
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    3
    Joint contracture
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Kyphoscoliosis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Kyphosis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Blister infected
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Bronchitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    4
    Bullous impetigo
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    COVID-19
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Catheter site abscess
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Catheter site infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    3
    Conjunctivitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Device related infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    3
    Ear infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    4
    Ear infection viral
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Eye infection
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Gastroenteritis viral
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Hordeolum
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    4 / 8 (50.00%)
         occurrences all number
    4
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 8 (37.50%)
         occurrences all number
    9
    Nasopharyngitis
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    5
    Oral candidiasis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Otitis media
         subjects affected / exposed
    3 / 8 (37.50%)
         occurrences all number
    12
    Otitis media acute
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    8
    Paronychia
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Pharyngitis
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    4
    Pneumonia
         subjects affected / exposed
    4 / 8 (50.00%)
         occurrences all number
    12
    Pneumonia influenzal
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Pustule
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Respiratory tract infection
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    3
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Rhinitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Rhinovirus infection
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Sepsis
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Sinusitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    5
    Urinary tract infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    8
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    2
    Varicella
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Vascular device infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    6
    Viral infection
         subjects affected / exposed
    5 / 8 (62.50%)
         occurrences all number
    9
    Viral tonsillitis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    2 / 8 (25.00%)
         occurrences all number
    2
    Bronchitis viral
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Diabetic ketoacidosis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Iron deficiency
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Metabolic alkalosis
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Type 1 diabetes mellitus
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1
    Vitamin D deficiency
         subjects affected / exposed
    1 / 8 (12.50%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Nov 2013
    Amendment 1 (Version 2.0, 19 November 2013) was implemented to modify the dose-escalation scheme of ALXN1101 to establish the safety and potential additional efficacy of higher doses of cPMP as ALXN1101 and determine the starting dose for future studies.
    27 Jan 2014
    Amendment 2 (Version 3.0, 27 January 2014) was implemented to add BP monitoring time points, the option of additional EEGs, and the added responsibility of the DMC to review all dose escalations, removal of references to specific starting doses, update visit windows, and clarify that after dose escalation was complete, a patient could be returned to the prior dose based on the patient’s clinical status at the discretion of the treating physician after consultation with the SRC.
    01 Oct 2015
    Amendment 3 (Version 4.0, 01 October 2015) was implemented to update the name of the Sponsor, medical monitor, and drug safety physician and revise the section describing the Bayley-III, MRI text, and blood sampling priority list, remove the post-Day 7 BP measurements by home infusion services, and update the AE severity assessment language to align with the protocol template.
    09 Dec 2016
    Amendment 4 (Version 5.0, 09 December 2016) was implemented to clarify the process for patient discontinuation in the event that ALXN1101 becomes registered and available as a treatment for MoCD Type A; extend the duration of the extension period; add additional assessments during the extension period; specify the infusion rate of ALXN1101 per FDA feedback on Protocol ALXN1101-202; specify that the NOAEL (10 mg/kg/day) determined from the 14-day adult rat toxicology study was used for dose justification since > 1 NOAEL has been determined across multiple species in nonclinical studies; add 12.5 mg/vial strength, clarify that the dose of ALXN1101 could be re-escalated to the final tolerated dose during the 60-month extension period in patients who were de-escalated for reasons other than PK or safety considerations; add a pre-dose PD sample collection to provide better characterization of PD data during the 60-month extension period; indicate that collection of the pre-dose PD sample would occur before the neurocognitive assessments, add an optional blood PK assessment at 24 hours after EOI on Day 1 and addition of PK assessment at 3 to 4 hours post-EOI at any visit during the 60-month extension period to better characterize PK at the designated time points; add sample blood volume tables during the 60-month extension period, safety follow-up visit, and an unscheduled dose adjustment.
    13 Jan 2017
    Amendment 5 (Version 6.0, 13 January 2017) was implemented to specify that a pre-dose PD blood sample was collected 1 time to better distinguish from other PD blood assessments collected at multiple clinical visits during the extension period; add a PK assessment at the EOI and 4 hours post-EOI during the 60-month extension period to better characterize PK; specify that neurological examination would also occur if there was an unscheduled dose adjustment; align the NOAEL across the program, including ALXN1101 IB Edition 4 and Protocol ALXN1101-MCD-202; and add WPPSI-IV assessments during the 60-month extension period to permit a more longitudinal assessment of intelligence for patients ≥ 3 years of age.
    23 Nov 2018
    Amendment 5.1 (Version 6.1, 23 November 2018) was implemented to update the drug name (ORGN001), title, Sponsor, and drug manufacturer information to reflect the new Sponsor, Origin Biosciences, Inc., who acquired the program from Alexion in September 2018.
    28 Jun 2019
    Amendment 6.0 (Version 7.0, 28 June 2019) was implemented to update Sponsor and medical monitor contact information, update the responsible medical officer, update the new clinical study leader and responsible physician, and remove all references limiting the extension period to 60 months.
    03 Jan 2020
    Amendment 7.0 (Version 8.0, 03 January 2020) was implemented to update text for the risk/benefit assessment.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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