Amyotrophic Lateral Sclerosis
Conditions
Keywords
Arimoclomol, ALS
Brief summary
A multicenter, non-randomized, open label trial, to assess long term safety and efficacy of Arimoclomol in subjects with Amyotrophic Lateral Sclerosis (ALS) who have completed the ORARIALS-01 trial.
Detailed description
The planned duration of the open-label trial was 152 weeks, but the trial was terminated early as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints. Therefore, the actual mean duration of open-label treatment was approximately 28 weeks (range approximately 2 to 71 weeks).
Interventions
DRUGArimoclomol
2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily
Sponsors
ZevraDenmark
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Non-randomized open label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures, or in the circumstance that the subject is incompetent, informed consent/assent is provided in accordance with local regulation and/or procedures * Subject has completed the ORARIALS-01 trial (i.e., met one of the surrogate survival endpoints of tracheostomy or PAV or has completed the 76 weeks randomized treatment period) * Subject completed ORARIALS-01 while on treatment, where on treatment is defined as having taken the last dose of IMP within 2 weeks of the End of Trial visit (whether at week 76 or prior)
Exclusion criteria
* Known or suspected allergy or intolerance to the IMP (Arimoclomol or constituents) * Exposure to any other investigational treatment, advanced therapy medicinal product or use of any other prohibited concomitant medications * Women who are lactating or pregnant, or men or women unwilling to use a highly effective method of birth control if not surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women; vasectomy for men) for female participants until 4 weeks after last dose and for male participants until 3 months after last dose. Pre-menopausal women must have a negative pregnancy test prior to dosing with trial medication. * Any of the following medically significant conditions: 1. Clinically significant renal or hepatic disease OR clinical laboratory assessment (results ≥ 3 times the upper limit of normal \[ULN\] for aspartate aminotransferase and/or alanine aminotransferase, bilirubin ≥ 2 times the ULN, or creatinine ≥ 1.5 times the ULN). 2. Any new condition or worsening of existing condition which, in the opinion of the investigator, would put the subject at undue risk. * Any serious adverse event or moderate/severe adverse event from the ORARIALS-01 trial which is ongoing at the time of transitioning to ORARIALS-02 and assessed as probably related to IMP
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks | The C-SSRS is a detailed questionnaire assessing both suicidal behavior and suicidal ideation through a series of simple, plain-language questions administered as an interview by a qualified investigator or delegate. |
| Mean and Change From Baseline in Vital Signs - Temperature | Week 76 | Standard vital signs measurement. |
| Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks | Clinical safety laboratory data and vital signs were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No patient was treated for 76 weeks. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks | Adverse event (AE) data were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No participant was treated for 76 weeks. Participants with on-treatment TEAEs are reported. An on-treatment TEAE is any TEAE in the on-treatment period defined as the time from first dose of IMP until 14 days since the last preceding administration of IMP (either before a temporary IMP interruption with duration \>14 days or the last dose at the end of trial). A participant may have several on-treatment periods separated by interruption intervals. |
| Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Week 76 | Standard hematology parameters. White blood cell differential count for basophils, eosinophils, leukocytes, lymphocytes, monocytes, and neutrophils, and platelet count. |
| Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Week 76 | Standard hematology parameters. Percentage of leukocytes were determined for basophils, eosinophils, lymphocytes, monocytes, and neutrophils |
| Mean and Change From Baseline in Clinical Safety Laboratory Tests - Erythrocytes | Week 76 | Standard hematology parameter. |
| Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematocrit | Week 76 | Standard hematology parameter. |
| Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hemoglobin | Week 76 | Standard hematology parameter. |
| Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Week 76 | Standard clinical chemistry parameters. Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase. |
| Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Week 76 | Standard clinical chemistry parameters. Calcium, Calcium Corrected, Cholesterol, Glucose, HDL Cholesterol, LDL Cholesterol, Potassium, Sodium, Triglycerides, and Urea Nitrogen. |
| Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3) | Week 76 | Standard clinical chemistry parameters. Bilirubin, Creatinine, Direct Bilirubin, and Indirect Bilirubin. |
| Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein | Week 76 | Standard clinical chemistry parameters. |
| Mean and Change From Baseline in Clinical Safety Laboratory Tests - Cystatin C | Week 76 | Standard clinical chemistry parameter. |
| Mean and Change From Baseline in Vital Signs - Blood Pressure | Week 76 | Standard vital signs. Systolic and diastolic blood pressure. |
| Mean and Change From Baseline in Vital Signs - Pulse Rate | Week 76 | Standard vital signs measurement. |
| Mean and Change From Baseline in Vital Signs - Respiratory Rate | Week 76 | Standard vital signs measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percentage (%) Predicted Slow Vital Capacity (SVC) From Baseline to Week 76 (for Subjects Who Did Not Meet the Survival Endpoint in the ORARIALS-01 Trial) | 76 weeks | Slow vital capacity (SVC) measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. Predicted SVC was derived per European Community of Coal and Steel (ECCS) reference equations: * If male: Predicted SVC = 0.061 x height (cm) - 0.028 x age (years) - 4.65 * If female: Predicted SVC = 0.0466 x height (cm) - 0.024 x age (years) - 3.28 |
| Change in ALS Functional Rating Scale - Revised (ALSFRS-R) From Baseline to Week 76 | Week 76 | The ALSFRS-R is an ordinal rating scale used to determine subjects' subjective assessment of their capability and independence with 12 functional activities ('speech', 'salivation', 'swallowing', handwriting', 'cutting food and handling utensils', 'dressing and hygiene', 'turning in bed and adjusting bed clothes', 'walking', 'dyspnoea', 'orthopnoea' and 'respiratory insufficiency'). Each activity is rated on a 5-point scale (from 0 \[no ability\] to 4 \[normal\]), giving a maximal ALSFRS-R score of 48. A lower score corresponds to a lower capability and independence. |
Countries
Belgium, Canada, France, Germany, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arimoclomol (Open-label) 248 mg arimoclomol base 3 times daily | 120 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 22 |
| Overall Study | Study terminated by sponsor | 87 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | Arimoclomol (Open-label) |
|---|---|
| Age, Continuous | 57.6 years STANDARD_DEVIATION 10.3 |
| ALS Functional Rating Scale - Revised (ALSFRS-R) | 26.0 units on a scale STANDARD_DEVIATION 10.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 38 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 39 Participants |
| Race (NIH/OMB) White | 80 Participants |
| Region of Enrollment Belgium | 5 participants |
| Region of Enrollment Canada | 2 participants |
| Region of Enrollment France | 17 participants |
| Region of Enrollment Germany | 7 participants |
| Region of Enrollment Italy | 14 participants |
| Region of Enrollment Netherlands | 10 participants |
| Region of Enrollment Poland | 15 participants |
| Region of Enrollment Spain | 15 participants |
| Region of Enrollment Sweden | 5 participants |
| Region of Enrollment United Kingdom | 2 participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 23 / 120 |
| other Total, other adverse events | 91 / 120 |
| serious Total, serious adverse events | 21 / 120 |
Outcome results
Primary
Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period
The C-SSRS is a detailed questionnaire assessing both suicidal behavior and suicidal ideation through a series of simple, plain-language questions administered as an interview by a qualified investigator or delegate.
Time frame: From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
Population: Safety analysis set: All enrolled patients who received at least one dose of arimoclomol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Completed Suicide | 0 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Suicidal ideation (yes on any 1 of the following 5 items) | 16 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Wish to be Dead | 15 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Non-specific active suicidal thoughts | 10 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Active Suicidal ideation with any methods (not Plan) without intent to Act | 5 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Active suicidal ideation with some intent, without Specific Plan | 1 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Active Suicidal ideation with specific Plan and Intent | 0 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Suicidal Behavior (yes on any 1 of the following 5 items) | 0 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Preparatory acts or behavior | 0 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Aborted Attempt | 0 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Interrupted Attempt | 0 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Actual Attempt (non-fatal) | 0 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Suicidal ideation or Behavior (yes to any of the above 10 items) | 16 Participants |
| Arimoclomol (Open-label) | Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period | Self-injurious Behavior without suicidal intent | 0 Participants |
Primary
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein
Standard clinical chemistry parameters.
Time frame: Week 76
Population: Data only available for 1 participant at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein | Albumin, Week 76 | 38.0 g/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein | Albumin, change from baseline to Week 76 | -13.0 g/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein | Protein, Week 76 | 64.0 g/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein | Protein, change from baseline to Week 76 | -16.0 g/L |
Primary
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1)
Standard clinical chemistry parameters. Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase.
Time frame: Week 76
Population: Data only available for 1 participant at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Alanine Aminotransferase, Week 76 | 14.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Alanine Aminotransferase, change from baseline to Week 76 | -31.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Alkaline Phosphatase, Week 76 | 97.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Alkaline Phosphatase, change from baseline to Week 76 | 16.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Aspartate Aminotransferase, Week 76 | 11.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Aspartate Aminotransferase, change from baseline to Week 76 | -15.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Creatine Kinase, Week 76 | 39.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Creatine Kinase, change from baseline to Week 76 | -118.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Gamma Glutamyl Transferase, Week 76 | 13.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Gamma Glutamyl Transferase, change from baseline to Week 76 | -15.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Lactate Dehydrogenase, Week 76 | 151.0 U/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) | Lactate Dehydrogenase, change from baseline to Week 76 | -42.0 U/L |
Primary
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2)
Standard clinical chemistry parameters. Calcium, Calcium Corrected, Cholesterol, Glucose, HDL Cholesterol, LDL Cholesterol, Potassium, Sodium, Triglycerides, and Urea Nitrogen.
Time frame: Week 76
Population: Data only available for 1 participant at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Calcium, Week 76 | 2.220 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Calcium, change from baseline to Week 76 | -0.350 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Calcium Corrected, Week 76 | 2.270 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Calcium Corrected, change from baseline to Week 76 | -0.080 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Cholesterol, Week 76 | 3.050 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Cholesterol, change from baseline to Week 76 | -1.060 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Glucose, Week 76 | 8.50 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Glucose, change from baseline to Week 76 | 1.60 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | HDL Cholesterol, Week 76 | 0.830 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | HDL Cholesterol, change from baseline to Week 76 | -0.770 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | LDL Cholesterol, Week 76 | 1.760 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | LDL Cholesterol, change from baseline to Week 76 | -0.540 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Potassium, Week 76 | 3.90 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Potassium, change from baseline to Week 76 | -0.50 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Sodium, Week 76 | 138.0 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Sodium, change from baseline to Week 76 | -6.0 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Triglycerides, Week 76 | 1.100 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Triglycerides, change from baseline to Week 76 | 0.320 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Urea Nitrogen, Week 76 | 4.60 mmol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) | Urea Nitrogen, change from baseline to Week 76 | -0.40 mmol/L |
Primary
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3)
Standard clinical chemistry parameters. Bilirubin, Creatinine, Direct Bilirubin, and Indirect Bilirubin.
Time frame: Week 76
Population: Data only available for 1 participant at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3) | Bilirubin, Week 76 | 5.0 micromol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3) | Bilirubin, change from baseline to Week 76 | -7.0 micromol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3) | Creatinine, Week 76 | 18.0 micromol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3) | Creatinine, change from baseline to Week 76 | -35.0 micromol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3) | Direct Bilirubin, Week 76 | 2.0 micromol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3) | Direct Bilirubin, change from baseline to Week 76 | -1.0 micromol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3) | Indirect Bilirubin, Week 76 | 3.0 micromol/L |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3) | Indirect Bilirubin, change from baseline to Week 76 | -6.0 micromol/L |
Primary
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Cystatin C
Standard clinical chemistry parameter.
Time frame: Week 76
Population: Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Cystatin C | Cystatin C, Week 76 | 1.310 mg/L | Standard Deviation 0.7495 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Cystatin C | Cystatin C, change from baseline to Week 76 | 0.350 mg/L | Standard Deviation 0.6364 |
Primary
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Erythrocytes
Standard hematology parameter.
Time frame: Week 76
Population: Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Erythrocytes | Erythrocytes, Week 76 | 3.70 10^12 cells/L | Standard Deviation 0 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Erythrocytes | Erythrocytes, change from baseline to Week 76 | -0.40 10^12 cells/L | Standard Deviation 0.707 |
Primary
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematocrit
Standard hematology parameter.
Time frame: Week 76
Population: Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematocrit | Hematocrit, Week 76 | 0.345 L of cells / L of blood | Standard Deviation 0.0071 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematocrit | Hematocrit, change from baseline to Week 76 | -0.025 L of cells / L of blood | Standard Deviation 0.0636 |
Primary
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1)
Standard hematology parameters. White blood cell differential count for basophils, eosinophils, leukocytes, lymphocytes, monocytes, and neutrophils, and platelet count.
Time frame: Week 76
Population: Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Basophils, Week 76 | 0.030 10^9 cells/L | Standard Deviation 0 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Basophils, change from baseline to Week 76 | -0.015 10^9 cells/L | Standard Deviation 0.0071 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Eosinophils, Week 76 | 0.150 10^9 cells/L | Standard Deviation 0.0141 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Eosinophils, change from baseline to Week 76 | -0.070 10^9 cells/L | Standard Deviation 0.0424 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Leukocytes, Week 76 | 9.120 10^9 cells/L | Standard Deviation 3.1537 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Leukocytes, change from baseline to Week 76 | -0.565 10^9 cells/L | Standard Deviation 2.4395 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Lymphocytes, Week 76 | 1.445 10^9 cells/L | Standard Deviation 0.4738 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Lymphocytes, change from baseline to Week 76 | -0.365 10^9 cells/L | Standard Deviation 0.3041 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Monocytes, Week 76 | 0.460 10^9 cells/L | Standard Deviation 0.1414 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Monocytes, change from baseline to Week 76 | -0.055 10^9 cells/L | Standard Deviation 0.0212 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Neutrophils, Segmented, Week 76 | 7.030 10^9 cells/L | Standard Deviation 3.4648 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Neutrophils, Segmented, change from baseline to Week 76 | -0.070 10^9 cells/L | Standard Deviation 2.8001 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Platelets, Week 76 | 334.0 10^9 cells/L | Standard Deviation 114.55 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) | Platelets, change from baseline to Week 76 | 62.5 10^9 cells/L | Standard Deviation 103.94 |
Primary
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2)
Standard hematology parameters. Percentage of leukocytes were determined for basophils, eosinophils, lymphocytes, monocytes, and neutrophils
Time frame: Week 76
Population: Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Basophils/Leukocytes, Week 76 | 0.40 percentage of leukocytes | Standard Deviation 0.141 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Basophils/Leukocytes, change from baseline to Week 76 | -0.05 percentage of leukocytes | Standard Deviation 0.212 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Eosinophils/Leukocytes, Week 76 | 1.70 percentage of leukocytes | Standard Deviation 0.424 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Eosinophils/Leukocytes, change from baseline to Week 76 | -0.50 percentage of leukocytes | Standard Deviation 0.849 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Lymphocytes/Leukocytes, Week 76 | 17.85 percentage of leukocytes | Standard Deviation 11.384 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Lymphocytes/Leukocytes, change from baseline to Week 76 | -0.95 percentage of leukocytes | Standard Deviation 8.132 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Monocytes/Leukocytes, Week 76 | 5.05 percentage of leukocytes | Standard Deviation 0.212 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Monocytes/Leukocytes, change from baseline to Week 76 | -0.20 percentage of leukocytes | Standard Deviation 1.556 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Neutrophils/Leukocytes, Week 76 | 74.95 percentage of leukocytes | Standard Deviation 12.092 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) | Neutrophils/Leukocytes, change from baseline to Week 76 | 1.70 percentage of leukocytes | Standard Deviation 10.607 |
Primary
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hemoglobin
Standard hematology parameter.
Time frame: Week 76
Population: Data only available for 2 participants at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hemoglobin | Hemoglobin, Week 76 | 115.5 g/L | Standard Deviation 3.54 |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hemoglobin | Hemoglobin, change from baseline to Week 76 | -14.0 g/L | Standard Deviation 21.21 |
Primary
Mean and Change From Baseline in Vital Signs - Blood Pressure
Standard vital signs. Systolic and diastolic blood pressure.
Time frame: Week 76
Population: Data only available for 1 participant at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Vital Signs - Blood Pressure | Systolic Blood Pressure, Week 76 | 112.0 mmHg |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Vital Signs - Blood Pressure | Systolic Blood Pressure, change from baseline to Week 76 | -10.0 mmHg |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Vital Signs - Blood Pressure | Diastolic Blood Pressure, Week 76 | 76.0 mmHg |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Vital Signs - Blood Pressure | Diastolic Blood Pressure, change from baseline to Week 76 | -1.0 mmHg |
Primary
Mean and Change From Baseline in Vital Signs - Pulse Rate
Standard vital signs measurement.
Time frame: Week 76
Population: Data only available for 1 participant at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Vital Signs - Pulse Rate | Pulse Rate, Week 76 | 86.0 beats/min |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Vital Signs - Pulse Rate | Pulse Rate, change from baseline to Week 76 | -3.0 beats/min |
Primary
Mean and Change From Baseline in Vital Signs - Respiratory Rate
Standard vital signs measurement.
Time frame: Week 76
Population: Data only available for 1 participant at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Vital Signs - Respiratory Rate | Respiratory Rate, Week 76 | 12.0 breaths/min |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Vital Signs - Respiratory Rate | Respiratory Rate, change from baseline to Week 76 | -4.0 breaths/min |
Primary
Mean and Change From Baseline in Vital Signs - Temperature
Standard vital signs measurement.
Time frame: Week 76
Population: Data only available for 1 participant at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arimoclomol (Open-label) | Mean and Change From Baseline in Vital Signs - Temperature | Temperature, Week 76 | 36.40 Degrees Celsius |
| Arimoclomol (Open-label) | Mean and Change From Baseline in Vital Signs - Temperature | Temperature, change from baseline to Week 76 | 0.80 Degrees Celsius |
Primary
Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period
Clinical safety laboratory data and vital signs were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No patient was treated for 76 weeks.
Time frame: From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
Population: Safety analysis set: All enrolled patients that received at least one dose of arimoclomol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Hemoglobin (g/L) <= 95 (Females) <= 115 (Males) | 10 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Hemoglobin (g/L) >= 165 (Females), >= 185 (Males) | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Erythrocytes (10^12/L) <= 3.5 (Females), <= 3.8 (Males) | 16 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Erythrocytes (10^12/L) >= 6.0 (Females), >= 7.0 (Males) | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Hematocrit <= 0.32 (Females), <= 0.37 (Males) | 21 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Hematocrit >= 0.5 (Females), >= 0.55 (Males) | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Leukocytes (10^9/L) <= 2.8 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Leukocytes (10^9/L) >= 16 | 3 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Neutrophils/Leukocytes (%) <= 20 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Neutrophils/Leukocytes (%) >= 85 | 3 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Eosinophils/Leukocytes (%) >= 10 | 1 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Basophils/Leukocytes (%) >= 10 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Lymphocytes/Leukocytes (%) <= 10 | 6 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Lymphocytes/Leukocytes (%) >= 75 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Monocytes/Leukocytes (%) >= 15 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Platelets (10^9/L) <= 75 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Platelets (10^9/L) >= 600 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Aspartate Aminotransferase (U/L) >= 3 x Upper Limit of Normal (ULN) | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Alanine Aminotransferase (U/L) >= 3 x ULN | 7 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Bilirubin (umol/L) >= 34 | 2 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Direct Bilirubin (umol/L) >= 12 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Indirect Bilirubin (umol/L) >= 22 | 4 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Alkaline Phosphatase (U/L) >= 3 x ULN | 1 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Gamma Glutamyl Transferase (U/L) >= 200 | 4 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Creatinine (umol/L) >= 1.5 x ULN | 1 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Urea Nitrogen (mmol/L) >= 11 | 7 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Sodium (mmol/L) <= 125 | 2 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Sodium (mmol/L) >= 155 | 1 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Potassium (mmol/L) <= 3.0 | 4 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Potassium (mmol/L) >= 6.0 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Calcium (mmol/L) <= 1.8 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Calcium (mmol/L) >= 3.0 | 2 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Glucose (mmol/L) <= 3.9 (Fasting=No or blank) | 8 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Glucose (mmol/L) >= 11.1 (Fasting=No or blank) | 7 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Glucose (mmol/L) <= 3.5 (Fasting=Yes) | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Glucose (mmol/L) >= 7.0 (Fasting=Yes) | 7 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Protein (g/L) <= 45 | 1 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Protein (g/L) >= 95 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Albumin (g/L) <= 27 | 2 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Cholesterol (mmol/L) >= 7.8 (Fasting=No or blank) | 15 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Cholesterol (mmol/L) >= 6.2 (Fasting=Yes) | 15 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Triglycerides (mmol/L) >= 5.65 (Fasting=No or blank) | 6 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Triglycerides (mmol/L) >= 4.2 (Fasting=Yes) | 3 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | LDL Cholesterol (mmol/L) >= 5.3 (Fasting=No or blank) | 13 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | LDL Cholesterol (mmol/L) >= 4.9 (Fasting=Yes) | 7 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | HDL Cholesterol (mmol/L) <= 0.8 (Fasting=No or blank) | 11 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | HDL Cholesterol (mmol/L) <= 0.9 (Fasting=Yes) | 2 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Creatine Kinase (U/L) >= 400 (Females) >= 750 (Males) | 20 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Lactate Dehydrogenase (U/L) >= 750 | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Pulse Rate <50 and decrease from baseline of >= 15 beats/min | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Pulse Rate >120 and increase from baseline of >= 15 beats/min | 0 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Diastolic Blood Pressure <=50 and decrease from baseline of >= 15 mmHg | 1 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Diastolic Blood Pressure >105 and increase from baseline of >= 15 mmHg | 6 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Systolic Blood Pressure <=90 and decrease from baseline of >= 20 mmHg | 3 Participants |
| Arimoclomol (Open-label) | Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period | Systolic Blood Pressure >180 and increase from baseline of >= 20 mmHg | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period
Adverse event (AE) data were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No participant was treated for 76 weeks. Participants with on-treatment TEAEs are reported. An on-treatment TEAE is any TEAE in the on-treatment period defined as the time from first dose of IMP until 14 days since the last preceding administration of IMP (either before a temporary IMP interruption with duration \>14 days or the last dose at the end of trial). A participant may have several on-treatment periods separated by interruption intervals.
Time frame: From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks
Population: Safety analysis set: All enrolled patients who received at least one dose of arimoclomol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | Treatment-emergent adverse events (TEAEs) | 93 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | Mild TEAEs | 34 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | Moderate TEAEs | 44 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | Severe TEAEs | 15 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | Treatment-related TEAEs | 31 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | Probably related TEAEs | 9 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | Possibly related TEAEs | 22 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | Not related TEAEs | 62 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | Serious TEAEs (SAEs) | 21 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | Treatment-related serious TEAEs | 1 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | TEAEs leading to IMP withdrawal | 9 Participants |
| Arimoclomol (Open-label) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period | TEAEs leading to IMP interruption | 12 Participants |
Secondary
Change in ALS Functional Rating Scale - Revised (ALSFRS-R) From Baseline to Week 76
The ALSFRS-R is an ordinal rating scale used to determine subjects' subjective assessment of their capability and independence with 12 functional activities ('speech', 'salivation', 'swallowing', handwriting', 'cutting food and handling utensils', 'dressing and hygiene', 'turning in bed and adjusting bed clothes', 'walking', 'dyspnoea', 'orthopnoea' and 'respiratory insufficiency'). Each activity is rated on a 5-point scale (from 0 \[no ability\] to 4 \[normal\]), giving a maximal ALSFRS-R score of 48. A lower score corresponds to a lower capability and independence.
Time frame: Week 76
Population: Data were not collected at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
Secondary
Change in Percentage (%) Predicted Slow Vital Capacity (SVC) From Baseline to Week 76 (for Subjects Who Did Not Meet the Survival Endpoint in the ORARIALS-01 Trial)
Slow vital capacity (SVC) measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. Predicted SVC was derived per European Community of Coal and Steel (ECCS) reference equations: * If male: Predicted SVC = 0.061 x height (cm) - 0.028 x age (years) - 4.65 * If female: Predicted SVC = 0.0466 x height (cm) - 0.024 x age (years) - 3.28
Time frame: 76 weeks
Population: Data only available for 1 patient at Week 76 since the trial was terminated early by the sponsor as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arimoclomol (Open-label) | Change in Percentage (%) Predicted Slow Vital Capacity (SVC) From Baseline to Week 76 (for Subjects Who Did Not Meet the Survival Endpoint in the ORARIALS-01 Trial) | -21.6 percentage of predicted SVC |