Phase 2
N=20
Long-Term Extension Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)
X-Linked Hypophosphatemia
Bottom Line
View on ClinicalTrials.gov: NCT02312687 ↗Enrolled (actual)
20
Serious AEs
45.0%
Results posted
Dec 2019
Primary outcome: Primary: Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death — 20; 20; 12; 9 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- KRN23 (Biological)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Kyowa Kirin, Inc.
- Primary completion
- Nov 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death |
20; 20; 12; 9; 1; 10 | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Vital Signs |
2; 1 | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category |
1; 1; 1; 1; 1; 1 | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category |
1; 1; 1; 1; 1; 1 | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests |
— | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in ECGs |
— | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category |
1; 1; 1; 2 | — |
| PRIMARY Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline |
2; 4; 0; 0 | — |
| PRIMARY Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing |
100 | — |
| PRIMARY Change From Baseline Over Time in Serum Phosphorus |
0.68; 0.68; 0.59; 0.47; 0.57; 0.59 | < 0.0001 sig |
| PRIMARY Change From Baseline Over Time in Serum iPTH |
-9.75; -11.17; -18.12; -25.28; -22.39; -28.33 | 0.1366 |
| PRIMARY Change From Baseline Over Time in Serum Total FGF23 |
215493.38; 202525.38; 221481.03; 221674.07; 208270.02; 235953.55 | < 0.0001 sig |
| PRIMARY Change From Baseline Over Time in Serum Free FGF23 |
1277.84; 1244.99; 1298.49; 1311.05; 1368.68; 1298.41 | < 0.0001 sig |
| PRIMARY Change From Baseline Over Time in Serum 1,25(OH)2D |
7.87; 2.70; 2.62; 0.31; -0.48; -3.43 | 0.0011 sig |
| PRIMARY Change From Baseline Ovr Time in 2-hour Urine TmP/GFR |
0.57; 0.47; 0.42; 0.44; 0.36; 0.47 | — |
| PRIMARY Change From Baseline Over Time in in 2-hour Urine TRP |
0.04; 0.01; 0.01; 0.05; 0.01; 0.02 | — |
| PRIMARY Change From Baseline Over Time in FEP |
-0.04; -0.01; -0.01; -0.05; -0.01; -0.02 | — |
| PRIMARY Change From Baseline Over Time in 24-hour Urine Phosphorus |
-0.01; 0.02; 0.08; -0.01; -0.01; -0.05 | — |
| PRIMARY Change From Baseline Over Time in 24-Hour Urine Calcium |
22.89; 15.15; 11.10; -16.65; 3.48; 28.55 | — |
| PRIMARY Change From Baseline Over Time in 24-Hour Urine Creatinine |
-14.77; -70.79; -16.11; -41.74; -76.11; -96.06 | — |
| PRIMARY Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio |
0.01; 0.01; 0.00; -0.01; 0.00; 0.03 | — |
| PRIMARY Change From Baseline Over Time in Total ALP |
14.92; -1.73; -22.28; -20.93; -18.77; -25.72 | 0.0314 sig |
| PRIMARY Change From Baseline Over Time in BALP |
4.68; -2.68; -7.45; -8.08; -10.01; -10.89 | 0.1673 |
| PRIMARY Change From Baseline Over Time in CTx |
343.38; 41.45; -61.96; -68.62; -53.41; -97.46 | 0.0113 sig |
| PRIMARY Change From Baseline Over Time in P1NP |
72.45; 44.40; 28.30; 27.02; 13.02; 43.12 | < 0.0001 sig |
Summary
The primary objectives of this study are to:
* Assess the long-term safety of KRN23 subcutaneous (SC) administration in adult subjects with XLH
* Assess the proportion of subjects achieving serum phosphorus levels in the normal range (2.5-4.5 mg/dL) with long-term administration of KRN23
* Assess long-term pharmacodynamics (PD) of KRN23 as measured by changes in the following: serum intact parathyroid hormone (iPTH); serum and urinary phosphorus; ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate (TmP/GFR) and tubular reabsorption of phosphate (TRP); serum 1,25-dihydroxy vitamin D (1,25[OH]2D); serum fibroblast growth factor 23 (FGF23); bone biomarkers: serum alkaline phosphatase (ALP), bone-specific ALP (BALP), carboxy terminal crosslinked telopeptide of type I collagen (CTx), and procollagen type 1 N-terminal propeptide (P1NP)
* Assess long-term immunogenicity of KRN23 as measured by presence of anti-KRN23 antibody (ADA)
Eligibility Criteria
Inclusion Criteria
- Have participated in Kyowa Hakko Kirin Pharma, Inc.'s KRN23-INT-001 (NCT01340482) or KRN23-INT-002 (NCT01571596) studies (received at least 2 doses of KRN23)
- Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min or eGFR of 45 to < 60 mL/min at Screening with confirmation that the renal insufficiency was not due to nephrocalcinosis.
- Sexually active subjects must be willing to use an acceptable method of contraception (e.g., double barrier method) while participating in the study and for 30 days after receiving the last dose of KRN23.
Exclusion Criteria
- Subject experienced a safety-related event in the KRN23-INT-001 or KRN23-INT-002 study that, in the opinion of the investigator and sponsor, precludes resuming KRN23 treatment.
- Presence of nephrocalcinosis on renal ultrasound that, in the opinion of the investigator and sponsor, precludes resuming KRN23 treatment.
- Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
- Participation in an investigational drug or device trial within 30 days of enrollment (other than KRN23-INT-001 or KRN23-INT-002).
- Use of a pharmacologic vitamin D metabolite or analog (e.g., calcitriol, doxercalciferol, and paricalcitol), phosphate, or aluminum hydroxide antacids (e.g., Maalox® and Mylanta®) within 21 days prior to Screening or during the study.
- Use of medication to suppress parathyroid hormone (PTH) (e.g., Sensipar®, cinacalcet, calcimimetics) within 2 months prior to Screening.
Data sourced from ClinicalTrials.gov (NCT02312687). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.