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Phase I/II, open-label, multicenter, multinational (Japan, Brazil and US),designed to evaluate the safety, pharmacokinetics and explore the efficacy for the treatment of mucopolysaccharidosis type I (MPS I).
In the JR-171-102 study, subjects will receive either 2.0 or 4.0 mg/kg/week of JR-171 intravenously at the same dosages received at Week 12 of the JR-171-101 study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part1 JR-171 | Experimental | Drug: JR-171 IV infusion, dose escalation |
|
| Part2 JR-171 | Experimental | Drug: JR-171 IV infusion, dose escalation, low dose, high dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JR-171 (lepunafusp alfa) | Drug | IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | Time of the first dose of JR-171 until the last visit (Week 5 for Part 1/ Week 13 for Part 2). |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of Each Dose in Part 1 (AUC0-t) | Week 1 to Week 4 | |
| Pharmacokinetics of Each Dose in Part 1 (Cmax) | Week 1 to Week 4 | |
| Pharmacokinetics of Each Dose in Part 2 (AUC0-t) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children's Hospital Oakland | Oakland | California | 94609 | United States | ||
| Hospital de Clínicas de Porto Alegre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38204164 | Derived | Harmatz P, Giugliani R, Martins AM, Hamazaki T, Kubo T, Kira R, Minami K, Ikeda T, Moriuchi H, Kawashima S, Takasao N, So S, Sonoda H, Hirato T, Tanizawa K, Schmidt M, Sato Y. alpha-L-iduronidase fused with humanized anti-human transferrin receptor antibody (lepunafusp alfa) for mucopolysaccharidosis type I: A phase 1/2 trial. Mol Ther. 2024 Mar 6;32(3):609-618. doi: 10.1016/j.ymthe.2024.01.009. Epub 2024 Jan 10. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Part1, Dose-escalation | JR-171, Dose-escalation:
|
| FG001 | Part 2, Dose-escalation | JR-171, Dose-escalation:
Participants are included as 4.0 mg/kg/week group. |
| FG002 | Part2, 2.0 mg | JR-171, 2.0 mg/kg/week group |
| FG003 | Part 2, 4.0 mg | JR-171, 4.0 mg/kg/week group |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part1, Dose-escalation | JR-171, Dose-escalation:
|
| BG001 | Part 2, Dose-escalation |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Number of Participants With Adverse Events | Since participants with dose-escalation treatment continued treatment with 4.0 mg/kg/week after the first three weeks, they were analyzed as 4.0 mg/kg/week group participants | Posted | Number | participants | Time of the first dose of JR-171 until the last visit (Week 5 for Part 1/ Week 13 for Part 2). |
|
Time of the first dose of JR-171 until the last visit (Week 5 for Part 1/ Week 13 for Part 2). Events occurring within 28 days after the time of observation at Week 5 in Part 1/Week 13 in Part 2 or discontinuation that are considered related to JR-171 will also be collected.
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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 | Part1, Dose-escalation | JR-171, Dose-escalation:
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac failure | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Influenza | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | JCR Pharmaceuticals | +81 797 32 8582 | clinical_development@jp.jcrpharm.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 12, 2021 | Mar 13, 2025 | Prot_SAP_002.pdf |
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| ID | Term |
|---|---|
| D008059 | Mucopolysaccharidosis I |
| ID | Term |
|---|---|
| D009083 | Mucopolysaccharidoses |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
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| Week 1 to Week 12 |
| Pharmacokinetics of Each Dose in Part 2 (Cmax) | Week 1 to Week 12 |
| Heparan Sulfate Concentrations in Cerebrospinal Fluid in Part 1 | Baseline to Week 4 |
| Dermatan Sulfate Concentrations in Cerebrospinal Fluid in Part 1 | Baseline to Week 4 |
| Heparan Sulfate Concentrations in Cerebrospinal Fluid in Part 2 | Baseline to Week 12 |
| Dermatan Sulfate Concentrations in Cerebrospinal Fluid in Part 2 | Baseline to Week 12 |
| Heparan Sulfate Concentrations in Serum in Part 1 | Baseline to Week 5 |
| Dermatan Sulfate Concentrations in Serum in Part 1 | Baseline to Week 5 |
| Heparan Sulfate Concentrations in Serum in Part 2 | Baseline to Week 13 |
| Dermatan Sulfate Concentrations in Serum in Part 2 | Baseline to Week 13 |
| Heparan Sulfate Concentrations in Urine in Part 1 | Baseline to Week 5 |
| Dermatan Sulfate Concentrations in Urine in Part 1 | Baseline to Week 5 |
| Heparan Sulfate Concentrations in Urine in Part 2 | Baseline to Week 13 |
| Dermatan Sulfate Concentrations in Urine in Part 2 | Baseline to Week 13 |
| Liver Volumes (Body Weight Adjusted) in Part 1 | Baseline to Week 5 |
| Spleen Volumes (Body Weight Adjusted) in Part 1 | Baseline to Week 5 |
| Liver Volumes (Body Weight Adjusted) in Part 2 | Baseline to Week 13 |
| Spleen Volumes (Body Weight Adjusted) in Part 2 | Baseline to Week 13 |
| Porto Alegre |
| Brazil |
| Instituto de Genética e Erros Inatos do Metabolismo - IGEIM | São Paulo | Brazil |
| Fukuoka Children's Hospital | Fukuoka | Japan |
| Kochi Medical School Hospital | Nankoku | Japan |
| Osaka Metropolitan University Hospital | Osaka | Japan |
JR-171, Dose-escalation:
Participants are included as 4.0 mg/kg/week group.
| BG002 | Part2, 2.0 mg | JR-171, 2.0 mg/kg/week group |
| BG003 | Part 2, 4.0 mg | JR-171, 4.0 mg/kg/week group |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Phenotype | Count of Participants | Participants |
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| Prior use of laronidase | Count of Participants | Participants |
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| HSCT treatment | Count of Participants | Participants |
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| Intellectual disabilities | Count of Participants | Participants |
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| Prior laronidase-related IAR | Count of Participants | Participants |
|
| Part 2, 4.0 mg |
JR-171, 4.0 mg/kg/week group 4.0 mg/kg/week group includes two participants with dose-escalation treatment for the first three weeks:
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| Secondary | Pharmacokinetics of Each Dose in Part 1 (AUC0-t) | Posted | Mean | Standard Deviation | h*ng/mL | Week 1 to Week 4 |
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| Secondary | Pharmacokinetics of Each Dose in Part 1 (Cmax) | Posted | Mean | Standard Deviation | ng/mL | Week 1 to Week 4 |
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| Secondary | Pharmacokinetics of Each Dose in Part 2 (AUC0-t) | There is no data for participants in dose-escalation group for plasma drug concentration after administration of JR-171. Though number of participants for PK set is 6 for each group, two participants from the 2.0 mg group and three participants from the 4.0 mg group was excluded from the data set since PK sample was collected by the same route as JR-171 administration and potential contamination could not be ruled out. | Posted | Mean | Standard Deviation | h*ng/mL | Week 1 to Week 12 |
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| Secondary | Pharmacokinetics of Each Dose in Part 2 (Cmax) | There is no data for participants in dose-escalation group for plasma drug concentration after administration of JR-171. Though number of participants for PK set is 6 for each group, two participants from the 2.0 mg group and three participants from the 4.0 mg group was excluded from the data set since PK sample was collected by the same route as JR-171 administration and potential contamination could not be ruled out. | Posted | Mean | Standard Deviation | ng/mL | Week 1 to Week 12 |
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| Secondary | Heparan Sulfate Concentrations in Cerebrospinal Fluid in Part 1 | Posted | Mean | Standard Deviation | ng/mL | Baseline to Week 4 |
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| Secondary | Dermatan Sulfate Concentrations in Cerebrospinal Fluid in Part 1 | Posted | Mean | Standard Deviation | ng/mL | Baseline to Week 4 |
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| Secondary | Heparan Sulfate Concentrations in Cerebrospinal Fluid in Part 2 | Since participants with dose-escalation treatment continued treatment with 4.0mg/kg/week after the first three weeks, they were analyzed as 4.0 mg/kg/group participants. Protocol visit was not performed at Week 12 by one participant in 4.0 mg group. | Posted | Mean | Standard Deviation | ng/mL | Baseline to Week 12 |
|
|
|
| Secondary | Dermatan Sulfate Concentrations in Cerebrospinal Fluid in Part 2 | Since participants with dose-escalation treatment continued treatment with 4.0mg/kg/week after the first three weeks, they were analyzed as 4.0 mg/kg/group participants. Protocol visit was not performed at Week 12 by one participant in 4.0 mg group. | Posted | Mean | Standard Deviation | ng/mL | Baseline to Week 12 |
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| Secondary | Heparan Sulfate Concentrations in Serum in Part 1 | Contamination happened with Heparin or Heparin-like compounds in one participant at Week 5. | Posted | Mean | Standard Deviation | ng/mL | Baseline to Week 5 |
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| Secondary | Dermatan Sulfate Concentrations in Serum in Part 1 | Posted | Mean | Standard Deviation | ng/mL | Baseline to Week 5 |
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| Secondary | Heparan Sulfate Concentrations in Serum in Part 2 | Participants are separated to S/H and Naive since these two will show a different trend of changes. Contamination happened with Heparin or Heparin-like compounds in 1 participant in 2.0 mg S/H group at W8 HS data were NA for 1 participant at W6(Not assessed), and another participant at W8, 10, 12, and 13(due to hospitalization) in 4.0 mg S/H group. Contamination happened in participant in 4.0 mg Naïve group at BL and W8, and HS data were not available at W4(due to difficult venous access). | Posted | Mean | Standard Deviation | ng/mL | Baseline to Week 13 |
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|
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| Secondary | Dermatan Sulfate Concentrations in Serum in Part 2 | Participants are separate to S/H and Naive in this table, since these two will show a different trend of changes. DS data were NA for one participant at W6 (Not assessed), and for another participant at Week 8, 10, 12, and 13 (due to hospitalization) in 4.0 mg Switched/HSCT group. DS data were NA at Week 4 due to difficult venous access in participant in 4.0 mg Naïve group. | Posted | Mean | Standard Deviation | ng/mL | Baseline to Week 13 |
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| Secondary | Heparan Sulfate Concentrations in Urine in Part 1 | Contamination happened with Heparin or Heparin-like compounds in one participant at Week 5. | Posted | Mean | Standard Deviation | µg/mgCr | Baseline to Week 5 |
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| Secondary | Dermatan Sulfate Concentrations in Urine in Part 1 | Posted | Mean | Standard Deviation | µg/mgCr | Baseline to Week 5 |
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| Secondary | Heparan Sulfate Concentrations in Urine in Part 2 | Participants are separated into S/H and Naive since it shows a different trend of changes. 4 participants data were excluded from analysis due to incorrect procedure of assessment (2 each for 2.0 and 4.0 mg S/H) Data were NA for 3 participants (1 at W12 (2.0 mg)[missing creatinine data] and 1 at W6 [No assessment], 1 at W8, 10, 12, 13 (4.0 mg S/H) [due to hospitalization]) Contamination happened in participant in 4.0 mg Naïve group at BL, and HS data were NA at W2, 4, 6 (due to creatinine BLD) | Posted | Mean | Standard Deviation | µg/mgCr | Baseline to Week 13 |
|
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| Secondary | Dermatan Sulfate Concentrations in Urine in Part 2 | Participants are separated into S/H and Naive since it shows a different trend of changes. 4 participants data were excluded from analysis due to incorrect procedure of assessment (2 each for 2.0 and 4.0 mg S/H) Data were NA for 3 participants (1 at W12 (2.0 mg)[missing creatinine data] and 1 at W6 [No assessment], 1 at W8, 10, 12, 13 (4.0 mg S/H) [due to hospitalization]). DS data were not available at W2, 4, and 6 (due to creatinine BLD) | Posted | Mean | Standard Deviation | µg/mgCr | Baseline to Week 13 |
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| Secondary | Liver Volumes (Body Weight Adjusted) in Part 1 | Posted | Mean | Standard Deviation | cm3/kg | Baseline to Week 5 |
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| Secondary | Spleen Volumes (Body Weight Adjusted) in Part 1 | Posted | Mean | Standard Deviation | cm3/kg | Baseline to Week 5 |
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| Secondary | Liver Volumes (Body Weight Adjusted) in Part 2 | Participants are separated to Switched/HSCT and Naive in this table, since these two will show a different trend of changes. Liver volume data were not available for one participant each in 2.0 mg and 4.0 mg Switched/HSCT group (One couldn't arrive at the site because of the weather and another was hospitalized). Another participant data in 4.0 mg Switched/HSCT group was excluded from analysis since assessment was performed out of the acceptable time frame. | Posted | Mean | Standard Deviation | cm3/kg | Baseline to Week 13 |
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| Secondary | Spleen Volumes (Body Weight Adjusted) in Part 2 | Participants are separated to Switched/HSCT and Naive in this table, since these two will show a different trend of changes. Spleen volume data were not available for one participant each in 2.0 mg and 4.0 mg Switched/HSCT group (One couldn't arrive at the site because of the weather and another was hospitalized). Another participant data in 4.0 mg Switched/HSCT group was excluded from analysis since assessment was performed out of the acceptable time frame. | Posted | Mean | Standard Deviation | cm3/kg | Baseline to Week 13 |
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| 0 |
| 4 |
| 0 |
| 4 |
| 3 |
| 4 |
| EG001 | Part2, 2.0 mg | JR-171, 2.0 mg/kg/week group | 1 | 6 | 1 | 6 | 6 | 6 |
| EG002 | Part 2, 4.0 mg | JR-171, 4.0 mg/kg/week group 4.0 mg/kg/week group includes two participants with dose-escalation treatment for the first three weeks:
Since participants with dose-escalation treatment continued treatment with 4.0mg/kg/week after the first three weeks, they were analyzed as 4.0 mg/kg/group participants. | 0 | 8 | 1 | 8 | 7 | 8 |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Cutaneous larva migrans | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Respiratory syncytial virus infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Device related infection | Infections and infestations | MedDRA (25.1) | Systematic Assessment |
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| Normocytic anaemia | Blood and lymphatic system disorders | MedDRA (25.1) | Systematic Assessment |
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| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA (25.1) | Systematic Assessment |
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| Aortic valve incompetence | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
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| Congestive cardiomyopathy | Cardiac disorders | MedDRA (25.1) | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (25.1) | Systematic Assessment |
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| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (25.1) | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Stasis dermatitis | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Spondylolisthesis | Musculoskeletal and connective tissue disorders | MedDRA (25.1) | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (25.1) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (25.1) | Systematic Assessment |
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| Blood iron decreased | Investigations | MedDRA (25.1) | Systematic Assessment |
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| CSF pressure increased | Investigations | MedDRA (25.1) | Systematic Assessment |
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| International normalised ratio increased | Investigations | MedDRA (25.1) | Systematic Assessment |
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| Transaminases increased | Investigations | MedDRA (25.1) | Systematic Assessment |
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| Lymphocyte morphology abnormal | Investigations | MedDRA (25.1) | Systematic Assessment |
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| Arthropod sting | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
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| Wound complication | Injury, poisoning and procedural complications | MedDRA (25.1) | Systematic Assessment |
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| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D016464 | Lysosomal Storage Diseases |
| D017520 | Mucinoses |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Week 12 |
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