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Trial record 1 of 2 for:    ORARIALS-01 Trial
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Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial

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ClinicalTrials.gov Identifier: NCT03836716
Recruitment Status : Recruiting
First Posted : February 11, 2019
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
Orphazyme

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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Arimoclomol Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 231 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Non-randomized open label
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label, Non-randomized Extension Trial to Assess Long Term Safety and Efficacy of Arimoclomol in Subjects With Amyotropic Lateral Sclerosis Who Have Completed the ORARIALS-01 Trial
Estimated Study Start Date : August 15, 2019
Estimated Primary Completion Date : August 1, 2022
Estimated Study Completion Date : August 1, 2022


Arm Intervention/treatment
Experimental: Arimoclomol
Arimoclomol, capsule
Drug: Arimoclomol
Active treatment
Other Name: Arimoclomol citrate




Primary Outcome Measures :
  1. Incidence and severity of Treatment-emergent adverse events (TEAEs) [ Time Frame: Over 76 weeks ]
    Treatment-emergent adverse events (TEAEs) summarized overall by seriousness, severity and relationship to treatment

  2. Mean and change from baseline to week 76 (or end of trial ) in Creatinine - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Creatinine, unit : (umol/L). Results are based on the last on-treatment value.

  3. Mean and change from baseline to week 76 (or end of trial ) in Bilirubin - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Bilirubin (direct, indirect, and total), unit : (umol/L). Results are based on the last on-treatment value.

  4. Mean and change from baseline to week 76 (or end of trial ) in Alanine aminotransferase (ALAT) - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Alanine aminotransferase (ALAT), unit: U/L. Results are based on the last on-treatment value.

  5. Mean and change from baseline to week 76 (or end of trial ) in Aspartate aminotransferase (ASAT) - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Aspartate aminotransferase (ASAT), unit: U/L. Results are based on the last on-treatment value.

  6. Mean and change from baseline to week 76 (or end of trial ) in Lactate dehydrogenase (LDH) - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Lactate dehydrogenase (LDH), unit: U/L. Results are based on the last on-treatment value.

  7. Mean and change from baseline to week 76 (or end of trial ) in Gamma-glutamyltransferase (GGT) - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Gamma-glutamyltransferase (GGT), unit: U/L. Results are based on the last on-treatment value.

  8. Mean and change from baseline to week 76 (or end of trial ) in Sodium - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Sodium, unit: mmol/L. Results are based on the last on-treatment value.

  9. Mean and change from baseline to week 76 (or end of trial ) in Potassium - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Potassium, unit: mmol/L. Results are based on the last on-treatment value.

  10. Mean and change from baseline to week 76 (or end of trial ) in Blood urea nitrogen (BUN) - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Blood urea nitrogen (BUN), unit : (mmol/L). Results are based on the last on-treatment value.

  11. Mean and change from baseline to week 76 (or end of trial ) in Calcium - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Calcium (total, albumin corrected calcium, ionised), unit : (mmol/L). Results are based on the last on-treatment value.

  12. Mean and change from baseline to week 76 (or end of trial ) in Albumin -(biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Albumin, unit: (g/L). Results are based on the last on-treatment value.

  13. Mean and change from baseline to week 76 (or end of trial ) in Total protein -(biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Total protein, unit: (g/L). Results are based on the last on-treatment value.

  14. Mean and change from baseline to week 76 (or end of trial ) in Creatine kinase (CK) - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Creatine kinase (CK), unit: (U/L). Results are based on the last on-treatment value.

  15. Mean and change from baseline to week 76 (or end of trial ) in Cystatin C - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Cystatin C, unit: (mg/L). Results are based on the last on-treatment value.

  16. Mean and change from baseline to week 76 (or end of trial ) in Glucose - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Glucose, unit: (mg/dL). Results are based on the last on-treatment value.

  17. Mean and change from baseline to week 76 (or end of trial ) in Lipids - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Low Density Lipoprotein (LDL), unit: (mmol/L). Results are based on the last on-treatment value.

  18. Mean and change from baseline to week 76 (or end of trial ) in Lipids - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in High Density Lipoprotein (HDL), unit: (mmol/L). Results are based on the last on-treatment value.

  19. Mean and change from baseline to week 76 (or end of trial ) in Lipids - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Triglycerides, unit: (mmol/L). Results are based on the last on-treatment value.

  20. Mean and change from baseline to week 76 (or end of trial ) in Cholesterol - (biochemistry) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Cholesterol, unit: (mmol/L). Results are based on the last on-treatment value.

  21. Mean and change from baseline to week 76 (or end of trial ) in Haemoglobin - (Haematology) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Haemoglobin, unit: (g/L). Results are based on the last on-treatment value.

  22. Mean and change from baseline to week 76 (or end of trial ) in Haematocrit - (Haematology) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Haematocrit, reference range: 0.34 - 0.48. Results are based on the last on-treatment value.

  23. Mean and change from baseline to week 76 (or end of trial ) in Thrombocytes - (Haematology) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Thrombocytes, unit: GI/L. Results are based on the last on-treatment value.

  24. Mean and change from baseline to week 76 (or end of trial ) in Erythrocytes - (Haematology) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Erythrocytes, unit: GI/L. Results are based on the last on-treatment value.

  25. Mean and change from baseline to week 76 (or end of trial ) in Leucocytes - (Haematology) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Leucocytes, unit: GI/L . Results are based on the last on-treatment value.

  26. Mean and change from baseline to week 76 (or end of trial ) in Eosinophils - (Haematology) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Eosinophils, measured by differential count in percentage (%). Results are based on the last on-treatment value.

  27. Mean and change from baseline to week 76 (or end of trial ) in Neutrophils - (Haematology) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Neutrophils, measured by differential count in percentage (%). Results are based on the last on-treatment value.

  28. Mean and change from baseline to week 76 (or end of trial ) in Basophils - (Haematology) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Basophils, measured by differential count in percentage (%). Results are based on the last on-treatment value.

  29. Mean and change from baseline to week 76 (or end of trial ) in Monocytes - (Haematology) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Monocytes, measured by differential count in percentage (%). Results are based on the last on-treatment value.

  30. Mean and change from baseline to week 76 (or end of trial ) in Lymphocytes - (Haematology) [ Time Frame: Over 76 weeks ]
    Mean and change from baseline in Lymphocytes, measured by differential count in percentage (%). Results are based on the last on-treatment value.

  31. Mean and change from baseline to week 76 (or end of trial ) in urinanalysis [ Time Frame: Over 76 weeks ]

    Clinical Safety Laboratory Tests includes a urinalysis panel measuring:

    Presence of blood in urine; results being positive or negative. Results are based on the last on-treatment value


  32. Mean and change from baseline to week 76 (or end of trial ) in urinanalysis [ Time Frame: Over 76 weeks ]

    Clinical Safety Laboratory Tests includes a urinalysis panel measuring:

    Presence of protein in urine; results being positive or negative. Results are based on the last on-treatment value


  33. Mean and change from baseline to week 76 (or end of trial ) in urinanalysis [ Time Frame: Over 76 weeks ]

    Clinical Safety Laboratory Tests includes a urinalysis panel measuring:

    Presence of glucose in urine; results being positive or negative. Results are based on the last on-treatment value


  34. Mean and change from baseline to week 76 (or end of trial ) in body weight [ Time Frame: Over 76 weeks ]
    Body weight will be measured in kilogram or pound (kg or lb). Results are based on the last on-treatment value

  35. Mean and change from baseline to week 76 (or end of trial ) in blood pressure [ Time Frame: Over 76 weeks ]
    Mean and change from baseline to week 76 (or end of trial ) in blood pressure measured in mmHG Results for each parameter are based on the last on-treatment value

  36. Mean and change from baseline to week 76 (or end of trial ) in pulse [ Time Frame: Over 76 weeks ]

    Mean and change from baseline to week 76 (or end of trial ) in pulse measured in beats per minute (BPM). Results are based on the last on-treatment value.

    Results for each parameter are based on the last on-treatment value


  37. Mean and change from baseline to week 76 (or end of trial ) in pulse [ Time Frame: Over 76 weeks ]

    Mean and change from baseline to week 76 (or end of trial ) in pulse measured in beats per minute (BPM) Results are based on the last on-treatment value.

    Results for each parameter are based on the last on-treatment value


  38. Incidence of potentially clinically significant abnormalities in body temperature [ Time Frame: Over 76 weeks ]
    Number of clinically significant abnormalities in in body temperature measured in degrees Celsius or Fahrenheit. Results are based on the last on-treatment value.

  39. Columbia-Suicide Severity Rating Scale (C-SSRS) over a treatment period of 76 weeks [ Time Frame: Over 76 weeks ]
    The C-SSRS is a detailed questionnaire assessing both suicidal behavior and suicidal ideation through a series of simple, plain language questions, where the scores range between 1-4 with 1 being lowest and 5 being highest of all assessments


Secondary Outcome Measures :
  1. Time to Permanent Assisted Ventilation (PAV)/tracheostomy/death /for subjects entering this trial having completed 76 weeks of randomized treatment in ORARIALS-01 [ Time Frame: Over 76 weeks ]
    Time from baseline to event where PAV is defined as the first of 7 consecutive days on which PAV was used for >22 hours/day for subjects having completed the 76 week treatment period in ORARIALS-01

  2. Change in ALS Functional Rating Scale Revised (ALSFRS-R) from Baseline to the end of the trial [ Time Frame: Over 76 weeks ]
    ALSFRS-R is an ordinal rating scale (0 through 4) used to determine the ALS patient's self assessment of their ability and need for assistance in 12 activities or functions. This is a validated scale, both in person and by phone, which provides a total score (best of 48) from 4 sub-scores which assess speech and swallowing, (bulbar function), use of upper extremities (cervical function), gait and turning in bed (lumbar function), and breathing (respiratory function).

  3. Change in Slow Vital Capacity (SVC) from Baseline to the end of the trial (for subjects who did not meet the survival endpoint in the ORARIALS-01 trial [ Time Frame: Over 76 weeks ]
    Change in Slow Vital Capacity (a measure of breathing function) over time



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  • On treatment with IMP defined as last dose within 2 weeks of the last visit of the blinded ORARIALS-01 trial.
  • Able and willing to travel to the site for the Baseline visit and in the investigator's opinion is expected to be able to attend the clinic for the visit at Week 4.

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
  • Significant protocol deviation in the blinded ORARIALS-01 trial based on the Investigator's judgement
  • 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, as indicated by clinical laboratory assessment (results ≥ 3 times the upper limit of normal [ULN] for aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, 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 make the subject unsuitable for enrolment or could interfere with the subject participating in or completing the trial
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03836716


Contacts
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Contact: Requests at Orphazyme A/S +45 39 17 82 72 Request@orphazyme.com

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Sponsors and Collaborators
Orphazyme
Investigators
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Principal Investigator: Michael Benatar, MD PhD University of Miami

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Responsible Party: Orphazyme
ClinicalTrials.gov Identifier: NCT03836716     History of Changes
Other Study ID Numbers: ORARIALS-02
First Posted: February 11, 2019    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Orphazyme:
Arimoclomol
ALS
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases