Study of KRN23 in Adults With X-linked Hypophosphatemia (XLH)
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| ClinicalTrials.gov Identifier: NCT02526160 |
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Recruitment Status :
Completed
First Posted : August 18, 2015
Results First Posted : February 5, 2021
Last Update Posted : February 5, 2021
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Sponsor:
Ultragenyx Pharmaceutical Inc
Collaborator:
Kyowa Kirin Co., Ltd.
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc
- Study Details
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| Study Type | Interventional |
|---|---|
| Study Design | Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment |
| Condition |
X-linked Hypophosphatemia |
| Interventions |
Biological: burosumab Other: Placebo |
| Enrollment | 134 |
Participant Flow
| Recruitment Details | |
| Pre-assignment Details |
| Arm/Group Title | Placebo | Burosumab 1 mg/kg |
|---|---|---|
 Arm/Group Description |
Subcutaneous (SC) injection of placebo every 4 weeks (Q4W) for 24 weeks (Double-blind Placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (Open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (Open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (Open-label Treatment Extension Period II). | SC injection of 1.0 mg/kg burosumab Q4W for 24 weeks (double-blind placebo-controlled Treatment Period), SC injection of burosumab 1 mg/kg Q4W for 24 weeks (open-label Treatment Continuation Period), SC injection of burosumab 1 mg/kg Q4W for 48 weeks (open-label Treatment Extension Period I), and SC injection of burosumab 1 mg/kg Q4W up to 53 weeks (open-label Treatment Extension Period II). |
| Period Title: Double-Blind (Placebo-Controlled) Period | ||
| Started | 66 | 68 |
| Completed | 66 | 67 |
| Not Completed | 0 | 1 |
| Reason Not Completed | ||
| Withdrawal by Subject | 0 | 1 |
| Period Title: Open-label Treatment Continuation Period | ||
| Started | 66 | 67 |
| Completed | 63 | 63 |
| Not Completed | 3 | 4 |
| Reason Not Completed | ||
| Withdrawal by Subject | 0 | 1 |
| Other, Not Specified | 3 | 3 |
| Period Title: Open-Label Treatment Extension Period I | ||
| Started | 63 | 63 |
| Completed | 60 | 59 |
| Not Completed | 3 | 4 |
| Reason Not Completed | ||
| Death | 0 | 1 |
| Other, Not Specified | 3 | 1 |
| Withdrawal by Subject | 0 | 1 |
| Lost to Follow-up | 0 | 1 |
| Period Title: Open-Label Treatment Extension Period II | ||
| Started | 52 | 49 |
| Completed | 51 | 49 |
| Not Completed | 1 | 0 |
| Reason Not Completed | ||
| Other, Not Specified | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Placebo | Burosumab | Total | |
|---|---|---|---|---|
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Arm/Group Description |
Placebo SC Q4W through Week 24 | Burosumab 1 mg/kg SC Q4W | Total of all reporting groups | |
| Overall Number of Baseline Participants | 66 | 68 | 134 | |
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Baseline Analysis Population Description |
[Not Specified]
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Age, Continuous
Mean (Standard Deviation) Unit of measure: Years |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| 38.65 (12.756) | 41.29 (11.582) | 39.99 (12.201) | ||
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Sex: Female, Male
Measure Type: Count of Participants Unit of measure: Participants |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| Female |
43 65.2%
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44 64.7%
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87 64.9%
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| Male |
23 34.8%
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24 35.3%
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47 35.1%
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Ethnicity (NIH/OMB)
Measure Type: Count of Participants Unit of measure: Participants |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| Hispanic or Latino |
5 7.6%
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7 10.3%
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12 9.0%
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| Not Hispanic or Latino |
61 92.4%
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61 89.7%
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122 91.0%
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| Unknown or Not Reported |
0 0.0%
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0 0.0%
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0 0.0%
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Race/Ethnicity, Customized
Measure Type: Count of Participants Unit of measure: Participants |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| Asian |
9 13.6%
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12 17.6%
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21 15.7%
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| Black or African American |
3 4.5%
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0 0.0%
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3 2.2%
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| White |
53 80.3%
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55 80.9%
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108 80.6%
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| Other, Not Specified |
1 1.5%
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1 1.5%
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2 1.5%
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Brief Pain Inventory (BPI) Worst Pain Score
[1] Mean (Standard Deviation) Unit of measure: Score on a scale |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| 6.54 (1.433) | 6.81 (1.308) | 6.68 (1.372) | ||
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[1]
Measure Description: The BPI evaluates the condition of all pain over the previous 24 hours. Question 3 of the short-form BPI (BPI-Q3) asks participants to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The baseline BPI Worst Pain is defined as the mean of the BPI Worst Pain for 8 days including the 7 days of diary scores prior to baseline visit and the baseline visit score.
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BPI Pain Severity Score
[1] Mean (Standard Deviation) Unit of measure: Score on a scale |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| 4.92 (1.547) | 5.18 (1.531) | 5.05 (1.539) | ||
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[1]
Measure Description: The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). The severity of pain in the last 24 hours is rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).
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BPI Pain Interference Score
[1] Mean (Standard Deviation) Unit of measure: Score on a scale |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| 4.76 (2.174) | 5.23 (2.237) | 5.00 (2.210) | ||
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[1]
Measure Description: The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Pain interference in the last 24 hours is rated on a scale of 0 (does not interfere) to 10 (completely interferes).
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Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score
[1] Mean (Standard Deviation) Unit of measure: Score on a scale |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| 61.36 (20.770) | 64.71 (20.253) | 63.06 (20.500) | ||
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[1]
Measure Description: The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst.
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WOMAC Physical Function Score
[1] Mean (Standard Deviation) Unit of measure: Score on a scale |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| 43.89 (19.938) | 50.79 (19.660) | 47.40 (20.024) | ||
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[1]
Measure Description: The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst.
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Brief Fatigue Inventory (BFI) Worst Fatigue Score
[1] Mean (Standard Deviation) Unit of measure: Score on a scale |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| 6.74 (1.526) | 6.94 (1.657) | 6.84 (1.591) | ||
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[1]
Measure Description: The BFI is a self-reported questionnaire consisting of 9 items related to fatigue rated on a 0 to 10 numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). Participants are asked to rate their worst fatigue over the past 24 hours from 0 (no fatigue) to 10 (as bad a you can imagine).
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BFI Global Fatigue Score
[1] Mean (Standard Deviation) Unit of measure: Score on a scale |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| 4.86 (1.932) | 5.37 (2.044) | 5.12 (1.999) | ||
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[1]
Measure Description: The BFI is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). BFI Global Fatigue score was calculated by averaging all 9 items on the BFI. Global scores range from 0 to 10, with higher score indicating worse fatigue severity and interference.
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Serum Procollagen Type 1 N- Propeptide (P1NP)
[1] Mean (Standard Deviation) Unit of measure: ng/mL |
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| Number Analyzed | 66 participants | 67 participants | 133 participants | |
| 87.6 (53.41) | 87.5 (53.60) | 87.6 (53.30) | ||
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[1]
Measure Analysis Population Description: participants with a baseline assessment
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Serum Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx)
[1] Mean (Standard Deviation) Unit of measure: pg/mL |
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| Number Analyzed | 66 participants | 67 participants | 133 participants | |
| 719.2 (419.24) | 718.4 (413.71) | 718.8 (414.89) | ||
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[1]
Measure Analysis Population Description: participants with a baseline assessment
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Serum Bone-Specific Alkaline Phosphatase (BALP)
[1] Mean (Standard Deviation) Unit of measure: μg/L |
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| Number Analyzed | 66 participants | 66 participants | 132 participants | |
| 24.6 (17.30) | 25.1 (21.55) | 24.9 (19.47) | ||
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[1]
Measure Analysis Population Description: participants with a baseline assessment
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Serum Phosphorus
Mean (Standard Deviation) Unit of measure: mmol/L |
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| Number Analyzed | 66 participants | 68 participants | 134 participants | |
| 0.617 (0.1001) | 0.653 (0.1072) | 0.635 (0.1050) | ||
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Serum 1, 25 (OH)2 D
[1] Mean (Standard Deviation) Unit of measure: pg/mL |
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| Number Analyzed | 64 participants | 66 participants | 130 participants | |
| 33.5 (15.61) | 32.4 (12.96) | 33.0 (14.28) | ||
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[1]
Measure Analysis Population Description: participants with a baseline assessment
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24-Hour Urinary Phosphorus
[1] Mean (Standard Deviation) Unit of measure: G/24 hour |
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| Number Analyzed | 65 participants | 68 participants | 133 participants | |
| 0.81 (0.262) | 0.72 (0.241) | 0.77 (0.255) | ||
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[1]
Measure Analysis Population Description: participants with a baseline assessment
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Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate(TmP/GFR)
[1] Mean (Standard Deviation) Unit of measure: mg/dL |
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| Number Analyzed | 64 participants | 66 participants | 130 participants | |
| 1.598 (0.3693) | 1.678 (0.4004) | 1.639 (0.3860) | ||
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[1]
Measure Analysis Population Description: participants with a baseline assessment
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Tubular Reabsorption of Phosphate (TRP)
[1] Mean (Standard Deviation) Unit of measure: Fraction of phosphate reabsorbed |
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| Number Analyzed | 64 participants | 67 participants | 131 participants | |
| 0.812 (0.0842) | 0.807 (0.0832) | 0.810 (0.0834) | ||
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[1]
Measure Analysis Population Description: participants with a baseline assessment
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Outcome Measures
Adverse Events
Limitations and Caveats
[Not Specified]
More Information
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts
the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title: | Medical Information |
| Organization: | Ultragenyx Pharmaceutical Inc |
| Phone: | 1-888-756-8657 |
| EMail: | medinfo@ultragenyx.com |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Ultragenyx Pharmaceutical Inc |
| ClinicalTrials.gov Identifier: | NCT02526160 |
| Other Study ID Numbers: |
UX023-CL303 2014-005529-11 ( EudraCT Number ) |
| First Submitted: | July 17, 2015 |
| First Posted: | August 18, 2015 |
| Results First Submitted: | December 17, 2020 |
| Results First Posted: | February 5, 2021 |
| Last Update Posted: | February 5, 2021 |