Not provided
Not provided
Not provided
Not provided
Not provided
As a consequence of the results of IBM4809 which did not meet any of its efficacy endpoints. The planned duration of open-label treatment was 40 months. After termination, the actual mean duration of treatment was approx. 28 weeks.
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Kansas Medical Center | OTHER |
| University College, London | OTHER |
Not provided
Not provided
Not provided
Not provided
A multicenter, nonrandomized, open-label, uncontrolled clinical extension trial designed to compare the efficacy and safety of early versus delayed start of arimoclomol in the treatment of Inclusion Body Myositis (IBM)
This was planned to be a 40-month open-label extension trial of the 20-month randomized, double-blind, placebo-controlled IBM4809 trial. The open-label trial was terminated early by the sponsor as a consequence of the results of IBM4809 which did not meet any of its efficacy endpoints. Therefore, the actual average duration of open-label treatment was approximately 28 weeks.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arimoclomol | Experimental | 248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Arimoclomol | Drug | 2 capsules (2 x 124 mg arimoclomol base; equivalent to 2 x 200 mg arimoclomol citrate) taken 3 times daily during breakfast, early afternoon, and at bedtime |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | The Inclusion Body Myositis Functional Rating Scale (IBMFRS) includes 10 measures (swallowing, handwriting, cutting food and handling utensils, fine motor tasks, dressing, hygiene, turning in bed and adjusting covers, changing position from sitting to standing, walking, and climbing stairs), each graded on a Likert scale from 0 (being unable to perform) to 4 (normal). The sum of the 10 items gives a value between 0 and 40. A higher score represents less functional limitation. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Six Minutes Walking Distance Test; Distance at 6 Minutes (6MWD) | Patients were instructed to walk down one side of a track and back along the opposite side as quickly and safely as possible for 6 minutes. Patients were allowed to take breaks as needed during the walking period, but timing continued during breaks. The distance walked in meters was recorded after 6 minutes. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Known or suspected allergy or intolerance to arimoclomol or its constituents.
Exposure to any other investigational treatment within 30 days or <5 half-lives of the baseline visit or taking part or planning to take part in another interventional trial.
Significant protocol deviation in the blinded IBM4809 trial based on the investigator's judgement in discussion with the medical monitor.
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 up to 3 months after last dose. Premenopausal women must have a negative pregnancy test prior to dosing with trial medication. Acceptable methods of birth control are:
Any concurrent condition that in the investigator's opinion will significantly interfere with assessment of safety or efficacy.
Inability to comply with the protocol-specified procedures/evaluations and scheduled visits as per the investigator.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Mazen M Dimachkie | University of Kansas Medical Center | Principal Investigator |
| Michael Hanna | University College, London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix Neurological Associates | Phoenix | Arizona | 85018 | United States | ||
| University of California |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Arimoclomol (Open-label) | Arimoclomol base 248 mg 3 times daily (planned duration 40 months; actual duration after early termination of the trial approx. 28 weeks). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 18, 2021 | May 12, 2023 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). |
| Change in Modified Timed Up and Go (mTUG) | The Modified Timed Up and Go (mTUG) measures the patient's ability to get up from a chair (allowing patients to use their arms), walk 3 meters, turn around, walk back to the chair, and sit down. The use of nearby walls or assistance from a caregiver was not allowed. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). |
| Change in Quadriceps Muscle Strength | Maximal voluntary isometric contraction testing (MVICT) of the patient's quadriceps muscle (extensor strength of the knee) were performed using a hand myometer which is a hand-held device that allows the examiner to push against a muscle while the patient resists. The test was performed on each side. The results for the stronger knee are reported here. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). |
| Change in Hand Grip Strength | Hand grip strength was assessed using a dynamometer. The test was performed on each hand. The grip strength of the stronger hand is reported here. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). |
| Change in the 36-Item Short Form Health Survey (SF-36) | The 36-Item Short Form Health Survey (SF-36) is a 36-item, patient-reported survey of health status. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol. No derived scores were calculated for SF-36 and no summary tabulation was done. | Change from Baseline in IBM-OLE to Early Termination Visit |
| Number of Falls and Near Falls | Patients recorded the number of falls and near falls in a falls diary. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol. No tabulation of falls and near falls was performed. | Baseline to Early Termination Visit |
| Irvine |
| California |
| 92697 |
| United States |
| University of Colorado School of Medicine | Aurora | Colorado | 80045 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| Johns Hopkins University | Baltimore | Maryland | 21218 | United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| The Ohio State University | Columbus | Ohio | 43221 | United States |
| Nerve and Muscle Center of Texas | Houston | Texas | 77030 | United States |
| University of Utah | Salt Lake City | Utah | 84112 | United States |
| University of Virginia | Charlottesville | Virginia | 22908 | United States |
| University College of London | London | WC1N 3BG | United Kingdom |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Safety population: All patients who received at least 1 dose or partial dose of arimoclomol in IBM-OLE.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Arimoclomol (Open-label) | Arimoclomol base 248 mg 3 times daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| |||||||||||||||||||||||
| Age at diagnosis | Mean | Standard Deviation | years |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score | The Inclusion Body Myositis Functional Rating Scale (IBMFRS) includes 10 measures (swallowing, handwriting, cutting food and handling utensils, fine motor tasks, dressing, hygiene, turning in bed and adjusting covers, changing position from sitting to standing, walking, and climbing stairs), each graded on a Likert scale from 0 (being unable to perform) to 4 (normal). The sum of the 10 items gives a value between 0 and 40. A higher score represents less functional limitation. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Patients in the modified intention-to-treat population with data for IBMFRS at the early termination visit | Posted | Mean | Standard Deviation | score on a scale | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). |
|
|
| |||||||||||||||||||||||||
| Secondary | Change in Six Minutes Walking Distance Test; Distance at 6 Minutes (6MWD) | Patients were instructed to walk down one side of a track and back along the opposite side as quickly and safely as possible for 6 minutes. Patients were allowed to take breaks as needed during the walking period, but timing continued during breaks. The distance walked in meters was recorded after 6 minutes. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Patients in the modified intention-to-treat population with data for the Six Minutes Walking distance test at the early termination visit | Posted | Mean | Standard Deviation | meters | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). |
|
| ||||||||||||||||||||||||||
| Secondary | Change in Modified Timed Up and Go (mTUG) | The Modified Timed Up and Go (mTUG) measures the patient's ability to get up from a chair (allowing patients to use their arms), walk 3 meters, turn around, walk back to the chair, and sit down. The use of nearby walls or assistance from a caregiver was not allowed. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Patients in the modified intention-to-treat population with data for the Modified Timed Up and Go (mTUG) at the early termination visit | Posted | Mean | Standard Deviation | meters/second | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). |
|
| ||||||||||||||||||||||||||
| Secondary | Change in Quadriceps Muscle Strength | Maximal voluntary isometric contraction testing (MVICT) of the patient's quadriceps muscle (extensor strength of the knee) were performed using a hand myometer which is a hand-held device that allows the examiner to push against a muscle while the patient resists. The test was performed on each side. The results for the stronger knee are reported here. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Patients in the modified intention-to-treat population with data for the Quadriceps Muscle Strength at the early termination visit | Posted | Mean | Standard Deviation | kg | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). |
|
| ||||||||||||||||||||||||||
| Secondary | Change in Hand Grip Strength | Hand grip strength was assessed using a dynamometer. The test was performed on each hand. The grip strength of the stronger hand is reported here. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol and data were only summarized descriptively. | Patients in the modified intention-to-treat population with data for the Hand Grip Strength test at the early termination visit | Posted | Mean | Standard Deviation | kg | Change from Baseline in IBM-OLE to Early Termination Visit (variable, an average of approximately 28 weeks). |
|
| ||||||||||||||||||||||||||
| Secondary | Change in the 36-Item Short Form Health Survey (SF-36) | The 36-Item Short Form Health Survey (SF-36) is a 36-item, patient-reported survey of health status. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol. No derived scores were calculated for SF-36 and no summary tabulation was done. | Since the double-blind lead-in trial (NCT02753530) did not meet any of its efficacy endpoints, the open-label extension trial was terminated prematurely, and the statistical analysis plan (SAP) was amended prior to database lock to align with the focus on safety recommended by FDA (Guidance for Industry: Submission of Abbreviated Reports and Synopses in Support of Marketing Applications). The amended SAP pre-specified that the SF-36 data would not be analyzed since it has no relevance to safety. | Posted | Change from Baseline in IBM-OLE to Early Termination Visit |
|
| |||||||||||||||||||||||||||||
| Secondary | Number of Falls and Near Falls | Patients recorded the number of falls and near falls in a falls diary. After the study was terminated early by the sponsor, the analyses of the efficacy endpoints were simplified from what was planned in the study protocol. No tabulation of falls and near falls was performed. | Since the double-blind lead-in trial (NCT02753530) did not meet any of its efficacy endpoints, the open-label extension trial was terminated prematurely, and the statistical analysis plan (SAP) was amended prior to database lock to align with the focus on safety recommended by FDA (Guidance for Industry: Submission of Abbreviated Reports and Synopses in Support of Marketing Applications). The amended SAP pre-specified that the falls data would not be analyzed since it has no relevance to safety. | Posted | Baseline to Early Termination Visit |
|
|
Adverse events (AEs) were collected from the first dose of study medication until 14 days following the latest administration of study medication. AEs were assessed monthly for the first 6 months, and then every second or third month. The time frame for collection of AEs was from Baseline in IBM-OLE to Early Termination (variable, an average of approximately 28 weeks).
The safety population included all participants who received any amount of study medication in IBM-OLE.
At each visit, the patient was allowed time to spontaneously report any issues since the last visit or evaluation. The investigator monitored and/or asked about or evaluated adverse events using non-leading questions.
Treatment-emergent adverse events were defined as adverse events with onset after the first dose of Investigational Medicinal Product (IMP) until the last dose of IMP +14 days.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arimoclomol (Open-label) | Arimoclomol base 248 mg 3 times daily | 2 | 121 | 13 | 121 | 97 | 121 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Corona virus infection | Infections and infestations | MedDRA Version 20.1. | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 20.1. | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA Version 20.1. | Systematic Assessment |
| |
| Electrocardiogram abnormal | Investigations | MedDRA Version 20.1. | Systematic Assessment |
| |
| B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 20.1. | Systematic Assessment |
| |
| Intraductal proliferative breast lesion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 20.1. | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 20.1. | Systematic Assessment |
| |
| Crohn's disease | Gastrointestinal disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Cervical vertebral fracture | Injury, poisoning and procedural complications | MedDRA Version 20.1. | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Tubulointerstitial nephritis | Renal and urinary disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA Version 20.1. | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Contusion | Injury, poisoning and procedural complications | MedDRA Version 20.1. | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA Version 20.1. | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA Version 20.1. | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA Version 20.1. | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA Version 20.1. | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA Version 20.1. | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA Version 20.1. | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 20.1. | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Affairs | Zevra Denmark A/S | +1-888-289-5607 | medicalaffairs@zevra.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 20, 2021 | May 12, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D018979 | Myositis, Inclusion Body |
| ID | Term |
|---|---|
| D009220 | Myositis |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C486387 | arimoclomol |
Not provided
Not provided
Not provided
| Black or African American |
|
| Native Hawaiian or Other Pacific Islander |
|
| White |
|
| Other |
|
| Multiple |
|
|
|
|
|