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The study was terminated early due to low enrollment and missing efficacy assessment data due to missed visits related to COVID-19.
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This study is designed to evaluate the safety and efficacy of deflazacort in participants with LGMD2I. Most participants enrolled will have a screening visit and 3 additional visits (after 1, 13, and 26 weeks of treatment).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Deflazacort | Experimental | Participants will receive deflazacort 0.6 milligrams per kilograms per day (mg/kg/day) orally. The dose could be reduced in case of tolerability issues. Any participant assigned to placebo prior to the Version 4.0 amendment (prior to or after 01 February 2020) will have the option to be consented under Version 4.0 and will be switched to deflazacort for 26 weeks treatment. Any participant assigned to deflazacort prior to the Version 4.0 amendment (prior to 01 February 2020) will have the option to re-consent under Protocol Version 4.0 and continue for an additional 26 weeks treatment. Any participant assigned to deflazacort prior to the Version 4.0 amendment (after 01 February 2020) will have the option to re-consent under Protocol Version 4.0 at their Week 13 Visit and continue treatment until Week 26. Any new participant enrolled until 31 May 2020 will receive deflazacort for 26 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Deflazacort | Drug | Deflazacort tablet will be administered as per the dose and schedule specified in the arm. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Time to Climb 4 Stairs After 26 Weeks of Treatment With Deflazacort | Baseline, Week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Forced Vital Capacity (FVC) After 26 Weeks of Treatment With Deflazacort | Baseline, Week 26 | |
| Change From Baseline in 2-Minute Walk Test After 26 Weeks of Treatment of Deflazacort | Baseline, Week 26 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Cristobal Passalacqua, MD | PTC Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rare Disease Research, LLC | Atlanta | Georgia | 30324 | United States | ||
| University of Iowa Hospitals and Clinics |
Participants enrolled under protocol v3.0 were 1:1 randomized to get placebo or deflazacort. After protocol v4.0, the study became an open-label study and all participants received deflazacort.
Per planned analysis, participants who took at least 1 dose of deflazacort were pooled in the safety and efficacy summaries.
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| ID | Title | Description |
|---|---|---|
| FG000 | Deflazacort | Participants received deflazacort tablets, administered orally once daily at a target dose of 0.6 milligrams (mg)/kilograms (kg)/day for 26 weeks in placebo-controlled period and for 26 weeks in open-label extension period. |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Placebo-Controlled Period (26 Weeks) |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 25, 2020 | Mar 1, 2022 |
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| Change From Baseline in Time to up and go After 26 Weeks of Treatment With Deflazacort | Baseline, Week 26 |
| Change From Baseline in Time to Descend 4 Stairs After 26 Weeks of Treatment With Deflazacort | Baseline, Week 26 |
| Change From Baseline in Time to Run/Walk 10 Meters After 26 Weeks of Treatment With Deflazacort | Baseline, Week 26 |
| Change From Baseline in Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) After 26 Weeks of Treatment With Deflazacort | Baseline, Week 26 |
| Change From Baseline in Hand-Held Myometry After 26 Weeks of Treatment With Deflazacort | Baseline, Week 26 |
| Change From Baseline in Global T2 Relaxation Time of Selected Upper and Lower Limb Muscles After 26 Weeks of Treatment With Deflazacort | Baseline, Week 26 |
| Number of Participants With Adverse Events (AEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. AEs were summarized separately for Stage 1 and for the overall ataluren experience. | Baseline up to Week 52 |
| Area Under the Concentration Curve From Time Zero to t (AUC0-t) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort | Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 |
| Area Under the Concentration Curve From Time Zero to Infinity (AUC0-inf) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort | Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 |
| Maximum Observed Plasma Concentration (Cmax) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort | Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 |
| Time to Reach Cmax (Tmax) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort | Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 |
| Half-Life (t1/2) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort | Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 |
| Iowa City |
| Iowa |
| 52242 |
| United States |
| The University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| Hugo W Moser Research Institute at Kennedy Krieger Institute | Baltimore | Maryland | 21205 | United States |
| University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| University of Washington | Seattle | Washington | 98195 | United States |
| University of Alberta | Edmonton | Alberta | T6G 2G3 | Canada |
| Ottawa Hospital | Ottawa | K1Y 4E9 | Canada |
| Rigshospitalet, University of Copenhagen | Copenhagen | 2200 | Denmark |
| CHRU de NANCY Service de Neurologie | France | 54035 | France |
| University Hospital La Timone | Marseille | 13385 | France |
| Ludwig-Maximilians University Munich, Friedrich-Baur-Institute | Munich | 80801 | Germany |
| Oslo University Hospital | Oslo | 0424 | Norway |
| Pirogov Russian National Research Medical University | Moscow | 125412 | Russia |
| Saint-Petersburg State Pediatric Medical University | Saint Petersburg | 194100 | Russia |
| Sahlgrenska University Hospital | Gothenburg | 41345 | Sweden |
Participants received placebo matched to deflazacort tablets, administered orally once daily for 26 weeks in placebo-controlled period. Participants were then transitioned to receive deflazacort tablets, administered orally once daily at a target dose of 0.6 mg/kg/day for 26 weeks in open-label extension period. |
| Safety Population | Safety population included all enrolled participants who received at least 1 dose of deflazacort. |
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| COMPLETED | Open-label transition |
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| NOT COMPLETED |
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| Open-Label Extension (26 Weeks) |
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Enrolled population included all informed-consented participants who met all inclusion and exclusion criteria.
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| ID | Title | Description |
|---|---|---|
| BG000 | Deflazacort | Participants received deflazacort tablets, administered orally once daily at a target dose of 0.6 mg/kg/day. |
| BG001 | Placebo | Participants received placebo matched to deflazacort tablets, administered orally once daily for 26 weeks in placebo-controlled period. Participants were then transitioned to receive deflazacort tablets, administered orally once daily at a target dose of 0.6 mg/kg/day for 26 weeks in open-label extension period. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 From Baseline in Time to Climb 4 Stairs After 26 Weeks of Treatment With Deflazacort | Safety population included all enrolled participants who received at least 1 dose of deflazacort. Here, 'Number analyzed' = participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | seconds | Baseline, Week 26 |
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| Secondary | Change From Baseline in Forced Vital Capacity (FVC) After 26 Weeks of Treatment With Deflazacort | Due to early termination of the study and missing efficacy assessment data due to missed visits related to COVID-19, data was not collected or analyzed for this secondary efficacy endpoint. | Posted | Baseline, Week 26 |
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| ||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in 2-Minute Walk Test After 26 Weeks of Treatment of Deflazacort | Safety population included all enrolled participants who received at least 1 dose of deflazacort. Here, 'Number analyzed' = participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | meters | Baseline, Week 26 |
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| Secondary | Change From Baseline in Time to up and go After 26 Weeks of Treatment With Deflazacort | Safety population included all enrolled participants who received at least 1 dose of deflazacort. Here, 'Number analyzed' = participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | seconds | Baseline, Week 26 |
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| Secondary | Change From Baseline in Time to Descend 4 Stairs After 26 Weeks of Treatment With Deflazacort | Safety population included all enrolled participants who received at least 1 dose of deflazacort. Here, 'Number analyzed' = participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | seconds | Baseline, Week 26 |
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| Secondary | Change From Baseline in Time to Run/Walk 10 Meters After 26 Weeks of Treatment With Deflazacort | Safety population included all enrolled participants who received at least 1 dose of deflazacort. Here, 'Number analyzed' = participants evaluable at specified timepoint. | Posted | Mean | Standard Deviation | seconds | Baseline, Week 26 |
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| Secondary | Change From Baseline in Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP) After 26 Weeks of Treatment With Deflazacort | Due to early termination of the study and missing efficacy assessment data due to missed visits related to COVID-19, data was not collected or analyzed for this secondary efficacy endpoint. | Posted | Baseline, Week 26 |
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| Secondary | Change From Baseline in Hand-Held Myometry After 26 Weeks of Treatment With Deflazacort | Due to early termination of the study and missing efficacy assessment data due to missed visits related to COVID-19, data was not collected or analyzed for this secondary efficacy endpoint. | Posted | Baseline, Week 26 |
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| Secondary | Change From Baseline in Global T2 Relaxation Time of Selected Upper and Lower Limb Muscles After 26 Weeks of Treatment With Deflazacort | Due to early termination of the study and missing efficacy assessment data due to missed visits related to COVID-19, data was not collected or analyzed for this secondary efficacy endpoint. | Posted | Baseline, Week 26 |
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| ||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events (AEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. AEs were summarized separately for Stage 1 and for the overall ataluren experience. | Safety population included all enrolled participants who received at least 1 dose of deflazacort. Per planned analysis, participants who took at least 1 dose of deflazacort were pooled in the safety summaries. The participants who received only placebo during the study were not included for safety analysis. | Posted | Count of Participants | Participants | Baseline up to Week 52 |
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| Secondary | Area Under the Concentration Curve From Time Zero to t (AUC0-t) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort | The pharmacokinetic (PK) population included all enrolled participants who received at least 1 dose of deflazacort and had at least one PK profile. Here, 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | nanograms (ng)*hour (hr)/milliliter (mL) | Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 |
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| Secondary | Area Under the Concentration Curve From Time Zero to Infinity (AUC0-inf) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort | The PK population included all enrolled participants who received at least 1 dose of deflazacort and had at least one PK profile. Here, 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | ng*hr/mL | Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort | The PK population included all enrolled participants who received at least 1 dose of deflazacort and had at least one PK profile. Here, 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | ng/mL | Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 |
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| Secondary | Time to Reach Cmax (Tmax) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort | The PK population included all enrolled participants who received at least 1 dose of deflazacort and had at least one PK profile. Here, 'Number analyzed' = participants evaluable for specified category. | Posted | Median | Full Range | hr | Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 |
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| Secondary | Half-Life (t1/2) of 21-desacetyl Deflazacort and 6β-hydroxy-21-desacetyl Deflazacort | The PK population included all enrolled participants who received at least 1 dose of deflazacort and had at least one PK profile. Here, 'Number analyzed' = participants evaluable for specified category. | Posted | Mean | Standard Deviation | hr | Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose at Baseline and Week 13 |
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Baseline up to Week 52
Safety population included all enrolled participants who received at least 1 dose of deflazacort. Per planned analysis, participants who took at least 1 dose of deflazacort were pooled in the safety summaries. The participants who received only placebo (not deflazacort) during the study were not monitored for safety assessments (including AE monitoring) per planned analysis.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Deflazacort | Participants received deflazacort tablets, administered orally once daily at a target dose of 0.6 mg/kg/day. | 0 | 7 | 0 | 7 | 5 | 7 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cushingoid | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Post-traumatic pain | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Skin laceration | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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| Weight increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Increased appetite | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Tension headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Visual field defect | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
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| Apathy | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Depressed mood | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Sleep disorder | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
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| Pollakiuria | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Amenorrhoea | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment | This is a gender-specific AE. Only female participants were at risk. |
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| Menstruation irregular | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment | This is a gender-specific AE. Only female participants were at risk. |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Abnormal hair growth | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Hirsutism | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
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The study was terminated early due to low enrollment and missing efficacy assessment data due to missed visits related to COVID-19.
The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Information | PTC Therapeutics, Inc. | 1-866-562-4620 | medinfo@ptcbio.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 28, 2020 | Mar 1, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D049288 | Muscular Dystrophies, Limb-Girdle |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C021988 | deflazacort |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Baseline |
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| Change at Week 26 |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Baseline |
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| Change at Week 26 |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Baseline |
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| Change at Week 26 |
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| Title | Denominators | Categories | ||||
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| Baseline |
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| Change at Week 26 |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| 21-desacetyl deflazacort: Baseline |
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| 21-desacetyl deflazacort: Week 13 |
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| 6β-hydroxy-21-desacetyl deflazacort: Week 1 |
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| 6β-hydroxy-21-desacetyl deflazacort: Week 13 |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| 21-desacetyl deflazacort: Baseline |
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| 21-desacetyl deflazacort: Week 13 |
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| 6β-hydroxy-21-desacetyl deflazacort: Week 1 |
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| 6β-hydroxy-21-desacetyl deflazacort: Week 13 |
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