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The primary purpose of this study is to assess the safety and efficacy of repeated subcutaneous (SC) injections of KRN23 in adult subjects with X-Linked Hypophosphatemia (XLH). A Bone Substudy will evaluate the effects of single-blind KRN23 versus Placebo on bone mineral density and bone quality.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| KRN23 | Experimental | Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KRN23 | Drug | Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor. |
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Efficacy of Repeated SC Injections of KRN23 | Safety and efficacy of repeated SC injections of KRN23 from baseline as assessed by serum phosphorus levels,immunogenicity, adverse events and clinically significant changes in vital signs and laboratory testing. | On-Treatment: 6.5 months, 27 total visits |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of Effect of Repeated SC Injections of KRN23 | Effect of repeated SC injections of KRN23, from baseline, on pharmacodynamic parameters including serum phosphorus, sex hormone, bone biomarkers, quality of life assessments and population pharmacokinetics of KRN23 dose levels from cumulative dosing. Summary of serum phosphorus by visit/day is captured below. | On-Treatment: 6.5 months, 27 total visits |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy | Evaluation of effect of repeated SC injections of KRN23, compared to Placebo on bone mineral density and bone quality. | On-Treatment: 6.5 months, 27 total visits |
Main Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amy Zhang, PhD | Kyowa Hakko Kirin Pharma, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Francisco Medical Center | San Francisco | California | 94143 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26073451 | Derived | Zhang X, Imel EA, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey J, Glorieux FH, Portale AA, Insogna K, Carpenter TO, Peacock M. Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody (KRN23) in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia. J Clin Pharmacol. 2016 Feb;56(2):176-85. doi: 10.1002/jcph.570. Epub 2015 Aug 11. | |
| 25919461 |
| Label | URL |
|---|---|
| KNR23-INT-002: An Extension Study of KRN23 in Adults With X-Linked Hypophosphatemia | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | KRN23 | Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor. |
| FG001 | Bone Substudy KRN23 | |
| FG002 | Bone Substudy Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | KRN23 | Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor. |
| BG001 |
| 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 | Safety and Efficacy of Repeated SC Injections of KRN23 | Safety and efficacy of repeated SC injections of KRN23 from baseline as assessed by serum phosphorus levels,immunogenicity, adverse events and clinically significant changes in vital signs and laboratory testing. | Posted | Count of Participants | Participants | On-Treatment: 6.5 months, 27 total visits |
|
Subjects were monitored for any untoward medical occurrences from the time of signed ICF through 30 days postdose.
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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 | KRN23 | Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses) KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Iron deficiency anaemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
Only 2 subjects were randomized in and completed the bone substudy. Subsequently, the Sponsor terminated the bone substudy due to slow accrual.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kyowa Kirin Pharmaceutical Development | Kyowa Kirin Pharmaceutical Development | 609-919-1100 | kkd.clintrial.82@kyowakirin.com |
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| ID | Term |
|---|---|
| D053098 | Familial Hypophosphatemic Rickets |
| ID | Term |
|---|---|
| D063730 | Rickets, Hypophosphatemic |
| D012279 | Rickets |
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
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| ID | Term |
|---|---|
| C000601956 | burosumab |
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| Yale University School of Medicine |
| New Haven |
| Connecticut |
| 06520 |
| United States |
| Clinical Research Center, Indiana University School of Medicine | Indianapolis | Indiana | 46202-5250 | United States |
| Duke Clinical Research Unit | Durham | North Carolina | 27710 | United States |
| University of Texas Health Science Center at Houston | Houston | Texas | 77030 | United States |
| Shriners Hospital for Children - Canada | Montreal | Quebec | H3G 1A6 | Canada |
| Derived |
| Imel EA, Zhang X, Ruppe MD, Weber TJ, Klausner MA, Ito T, Vergeire M, Humphrey JS, Glorieux FH, Portale AA, Insogna K, Peacock M, Carpenter TO. Prolonged Correction of Serum Phosphorus in Adults With X-Linked Hypophosphatemia Using Monthly Doses of KRN23. J Clin Endocrinol Metab. 2015 Jul;100(7):2565-73. doi: 10.1210/jc.2015-1551. Epub 2015 Apr 28. |
| Bone Substudy KRN23 |
| BG002 | Bone Substudy Placebo |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Bone Substudy Placebo |
|
|
| Secondary | Evaluation of Effect of Repeated SC Injections of KRN23 | Effect of repeated SC injections of KRN23, from baseline, on pharmacodynamic parameters including serum phosphorus, sex hormone, bone biomarkers, quality of life assessments and population pharmacokinetics of KRN23 dose levels from cumulative dosing. Summary of serum phosphorus by visit/day is captured below. | Efficacy analysis set: All subjects who received at least 1 dose of KRN23 and completed at least one 28-day post-dose evaluation. | Posted | Mean | Full Range | mg/dL | On-Treatment: 6.5 months, 27 total visits |
|
|
|
| Other Pre-specified | Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy | Evaluation of effect of repeated SC injections of KRN23, compared to Placebo on bone mineral density and bone quality. | Subjects randomized to the bone density substudy | Posted | Number | units on a scale | On-Treatment: 6.5 months, 27 total visits |
|
|
|
| 0 |
| 27 |
| 0 |
| 27 |
| 24 |
| 27 |
| EG001 | Bone Substudy KRN23 | 0 | 1 | 0 | 1 | 1 | 1 |
| EG002 | Bone Substudy Placebo | 0 | 1 | 0 | 1 | 1 | 1 |
| Ear pain | Ear and labyrinth disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sensitivity of teeth | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lip ulceration | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vessel puncture site haematoma | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Feeling hot | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Feeling cold | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Malaise | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Local swelling | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Oedema peripheral | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pyrexia | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Injection site urticaria | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Injection site erythema | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Injection site reaction | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Injection site pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Influenza like illness | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Ear infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Laryngitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Viral infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Post procedural infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Post-traumatic pain | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Blood triglycerides increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Ligament pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Spinal column stenosis | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Exostosis | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Visual field defect | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Restless legs syndrome | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Presyncope | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Migraine | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Burning sensation | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pregnancy | Pregnancy, puerperium and perinatal conditions | CTCAE (4.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Polyuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Tonsillar hypertrophy | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sinus disorder | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pleurisy | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Painful respiration | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cold sweat | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D009140 |
| Musculoskeletal Diseases |
| D007015 | Hypophosphatemia, Familial |
| D015499 | Renal Tubular Transport, Inborn Errors |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D008664 | Metal Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D002128 | Calcium Metabolism Disorders |
| D017674 | Hypophosphatemia |
| D010760 | Phosphorus Metabolism Disorders |
| D014808 | Vitamin D Deficiency |
| D001361 | Avitaminosis |
| D003677 | Deficiency Diseases |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |
|
| Visit 4 (D7)/7 |
|
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| Visit 5 (D12)/12 |
|
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| Visit 6 (D18)/18 |
|
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| Visit 7 (D26)/26 |
|
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| Visit 8 (D28)/0 |
|
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| Visit 9 (D31)/3 |
|
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| Visit 10 (D35)/7 |
|
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| Visit 11 (D40)/12 |
|
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| Visit 12 (D46)/18 |
|
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| Visit 13 (D54)/26 |
|
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| Visit 14 (D56)/0 |
|
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| Visit 15 (D59)/3 |
|
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| Visit 16 (D63)/7 |
|
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| Visit 17 (D68)/12 |
|
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| Visit 18 (D74)/18 |
|
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| Visit 19 (D82)/26 |
|
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| Visit 20 (D84)/0 |
|
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| Visit 21 (D87)/3 |
|
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| Visit 22 (D91)/7 |
|
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| Visit 23 (D96)/12 |
|
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| Visit 24 (D102)/18 |
|
|
| Visit 25 (D110)/26 |
|
|
| End of Study - Visit 26 (D120) |
|
|
| Early Withdrawal |
|
|