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The purpose of this study is to see whether PRO044 is safe and effective to use as medication for DMD patients with a mutation around location 44 in the DNA for the dystrophin protein.
To assess the effect of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To assess the safety and tolerability of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To determine the pharmacokinetics of PRO044 at different dose levels after subcutaneous and intravenous administration in subjects with Duchenne muscular dystrophy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PRO044, cohort 1 | Experimental | Subcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29. |
|
| PRO044, cohort 2 | Experimental | Subcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29. |
|
| PRO044, cohort 3 | Experimental | Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29. |
|
| PRO044, cohort 4 | Experimental | Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29. |
|
| PRO044, cohort 5 | Experimental | Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29 |
|
| PRO044, cohort 6 | Experimental | Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PRO044 SC | Drug | Subcutaneous injection, once a week, for five weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts | Within 13 weeks after 5 weeks of treatment | |
| Safety and Tolerability of PRO044 | number of subjects with 1 or more treatment emergent adverse events following SC or IV PRO044 | During the 5 weeks of treatment and during the 13 weeks after treatment |
| Measure | Description | Time Frame |
|---|---|---|
| PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration | Pharmacokinetic population evaluated for maximum plasma concentration (Cmax) | Week 1, Week 5 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| A. Ferlini, PhD | Università di Ferrara and S.Anna Hospital, Ferrara, Italy | Principal Investigator |
| J. J. Verschuuren, MD | Leiden University Medical Center, Leiden, the Netherlands | Principal Investigator |
| N. Goemans, MD | UZ Leuven, Leuven, Belgium | Principal Investigator |
| M. Tulinius, MD | The Queen Silvia Children's Hospital, Gothenburg, Sweden | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UZ Leuven | Leuven | 3000 | Belgium | |||
| S.Anna Hospital |
3 Subjects were recruited to each of cohorts 1-6 (total n=18) for SC administration PRO044 9 of these 18 subjects were recruited to cohorts 7-9 (n=3 in each cohort) for IV adminstration PRO044
3 Subjects were recruited to each of cohorts 1-6 (total n=18) for SC administration PRO044 9 of these 18 subjects were recruited to cohorts 7-9 (n=3 in each cohort) for IV adminstration PRO044
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| ID | Title | Description |
|---|---|---|
| FG000 | Subcutaneous PRO044 0.5 mg/kg | Subcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| FG001 | Subcutaneous PRO044 1.5 mg/kg | Subcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| FG002 | Subcutaneous PRO044 5 mg/kg | Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| FG003 | Subcutaneous PRO044 8 mg/kg | Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| FG004 | Subcutaneous PRO044 10 mg/kg | Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29 PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| FG005 | Subcutaneous PRO044 12 mg/kg | Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29 PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| FG006 | Intravenous PRO044 1.5 mg/kg | Intravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29 PRO044 IV: Intravenous injection, once a week, for five weeks |
| FG007 | Intravenous PRO044 5 mg/kg | Intravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29 PRO044 IV: Intravenous injection, once a week, for five weeks |
| FG008 | Intravenous PRO044 8 mg/kg | Intravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29 PRO044 IV: Intravenous injection, once a week, for five weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subcutaneous Cohort 1 - 6 |
| |||||||||||||
| Intravenous Period 7 - 9 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | PRO044, Cohort 1 | Subcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| BG001 | PRO044, Cohort 2 | Subcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| 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 |
| 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 | Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts | For some participants it was not possible to determine dystrophin expression in muscle biopsy | Posted | Count of Participants | Participants | Within 13 weeks after 5 weeks of treatment |
|
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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 | PRO044, Cohort 1 | Subcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Concussion | Injury, poisoning and procedural complications | fell over in playground |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site hematoma | General disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Fiona Lawrence | Prosensa | +31(0)713322100 | f.lawrence@prosensa.nl |
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| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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|
| PRO044, cohort 7 | Experimental | Intravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29 |
|
| PRO044, cohort 8 | Experimental | Intravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29 |
|
| PRO044, cohort 9 | Experimental | Intravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29 |
|
| PRO044 IV | Drug | Intravenous injection, once a week, for five weeks |
|
| Ferrara |
| Italy |
| Leiden University Medical Center | Leiden | 2300 | Netherlands |
| The Queen Silvia Children's Hospital | Gothenburg | Sweden |
| COMPLETED |
|
| NOT COMPLETED |
|
| BG002 | PRO044, Cohort 3 | Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| BG003 | PRO044, Cohort 4 | Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| BG004 | PRO044, Cohort 5 | Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29 PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| BG005 | PRO044, Cohort 6 | Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29 PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | PRO044, Cohort 3 | Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| OG003 | PRO044, Cohort 4 | Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| OG004 | PRO044, Cohort 5 | Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29 PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| OG005 | PRO044, Cohort 6 | Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29 PRO044 SC: Subcutaneous injection, once a week, for five weeks |
| OG006 | PRO044, Cohort 7 | Intravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29 PRO044 IV: Intravenous injection, once a week, for five weeks |
| OG007 | PRO044, Cohort 8 | Intravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29 PRO044 IV: Intravenous injection, once a week, for five weeks |
| OG008 | PRO044, Cohort 9 | Intravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29 PRO044 IV: Intravenous injection, once a week, for five weeks |
|
|
| Primary | Safety and Tolerability of PRO044 | number of subjects with 1 or more treatment emergent adverse events following SC or IV PRO044 | Posted | Count of Participants | Participants | During the 5 weeks of treatment and during the 13 weeks after treatment |
|
|
|
| Secondary | PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration | Pharmacokinetic population evaluated for maximum plasma concentration (Cmax) | Pharmacokinetic population evaluated | Posted | Geometric Mean | Geometric Coefficient of Variation | ug/mL | Week 1, Week 5 |
|
|
|
| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | PRO044, Cohort 2 | Subcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks | 0 | 3 | 3 | 3 |
| EG002 | PRO044, Cohort 3 | Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks | 1 | 3 | 3 | 3 |
| EG003 | PRO044, Cohort 4 | Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29. PRO044 SC: Subcutaneous injection, once a week, for five weeks | 0 | 3 | 3 | 3 |
| EG004 | PRO044, Cohort 5 | Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29 PRO044 SC: Subcutaneous injection, once a week, for five weeks | 0 | 3 | 3 | 3 |
| EG005 | PRO044, Cohort 6 | Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29 PRO044 SC: Subcutaneous injection, once a week, for five weeks | 0 | 3 | 3 | 3 |
| EG006 | PRO044, Cohort 7 | Intravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29 PRO044 IV: Intravenous injection, once a week, for five weeks | 0 | 3 | 2 | 3 |
| EG007 | PRO044, Cohort 8 | Intravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29 PRO044 IV: Intravenous injection, once a week, for five weeks | 0 | 3 | 3 | 3 |
| EG008 | PRO044, Cohort 9 | Intravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29 PRO044 IV: Intravenous injection, once a week, for five weeks | 0 | 3 | 3 | 3 |
| International normalised ratio increased | Blood and lymphatic system disorders |
|
| activated partial thromboplastin time prolonged | Blood and lymphatic system disorders |
|
| orthostatic proteinuria | Renal and urinary disorders |
|
| Injection site erythema | General disorders |
|
| Injection site edema | General disorders |
|
| Injection site pain | General disorders |
|
| Performance status decreased | General disorders |
|
| Application site erythema | General disorders |
|
| Influenza like illness | General disorders |
|
| Pyrexia | General disorders |
|
| Injection site discoloration | General disorders |
|
| Injection site pruritus | General disorders |
|
| Injection site urticaria | General disorders |
|
| Asthenia | General disorders |
|
| Fatigue | General disorders |
|
| Injection site induration | General disorders |
|
| Localized edema | General disorders |
|
| Edema peripheral | General disorders |
|
| Nasopharyngitis | Infections and infestations |
|
| Influenza | Infections and infestations |
|
| Pharyngitis | Infections and infestations |
|
| Pneumonia | Infections and infestations |
|
| Hookworm infection | Infections and infestations |
|
| Upper respiratory tract infection | Infections and infestations |
|
| Gastroenteritis | Infections and infestations |
|
| Rhinitis | Infections and infestations |
|
| Varicella | Infections and infestations |
|
| Procedural pain | Injury, poisoning and procedural complications |
|
| Contusion | Injury, poisoning and procedural complications |
|
| Fall | Injury, poisoning and procedural complications |
|
| Post procedural edema | Injury, poisoning and procedural complications |
|
| Post-traumatic pain | Injury, poisoning and procedural complications |
|
| Complement factor decreased | Investigations |
|
| aPTT prolonged | Investigations |
|
| INR increased | Investigations |
|
| Monocyte count decreased | Investigations |
|
| Neutrophil count increased | Investigations |
|
| RBC urine positive | Investigations |
|
| Laboratory test abnormal (elevated MCP-1 levels) | Investigations |
|
| Complement factor C3 decreased | Investigations |
|
| Cystatin C increased | Investigations |
|
| Electrocardiogram T wave amplitude decreased | Investigations |
|
| GLDH increased | Investigations |
|
| Urine protein/creatinine ratio increased | Investigations |
|
| WBC count increased | Investigations |
|
| Headache | Nervous system disorders |
|
| Dizziness | Nervous system disorders |
|
| Proteinuria | Renal and urinary disorders |
|
| Dysuria | Renal and urinary disorders |
|
| Glycosuria | Renal and urinary disorders |
|
| Microalbuminuria | Renal and urinary disorders |
|
| Myoglobinuria | Renal and urinary disorders |
|
| Orthostatic proteinuria | Renal and urinary disorders |
|
| Abdominal pain | Gastrointestinal disorders |
|
| Abdominal pain upper | Gastrointestinal disorders |
|
| Diarrhea | Gastrointestinal disorders |
|
| Dyspepsia | Gastrointestinal disorders |
|
| Vomiting | Gastrointestinal disorders |
|
| Erythema | Skin and subcutaneous tissue disorders |
|
| Rash | Skin and subcutaneous tissue disorders |
|
| Skin swelling | Skin and subcutaneous tissue disorders |
|
| Panniculitis | Skin and subcutaneous tissue disorders |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders |
|
| Back pain | Musculoskeletal and connective tissue disorders |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders |
|
| Arthralgia | Musculoskeletal and connective tissue disorders |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders |
|
| Cough | Respiratory, thoracic and mediastinal disorders |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders |
|
| Acquired hydrocele | Reproductive system and breast disorders |
|
| Pallor | Vascular disorders |
|
| Insomnia | Psychiatric disorders |
|
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| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| Week 5 |
|