Safety and Efficacy of Hectorol in Pediatric Patients With Chronic Kidney Disease Stage 3 and 4 With Secondary Hyperparathyroidism Not Yet on Dialysis

An Open-Label, Randomized, Parallel Group Study to Assess the Safety and Efficacy of Hectorol® (Doxercalciferol Capsules) in Pediatric Patients With Chronic Kidney Disease Stages 3 and 4 With Secondary Hyperparathyroidism Not Yet on Dialysis

Primary Objective:

Evaluated the effect of Hectorol® capsules in reducing elevated levels of intact parathyroid hormone (iPTH).

Secondary Objectives:

• Evaluated the safety profile of Hectorol® capsules versus Rocaltrol® (calcitriol) capsules.
• Determined the pharmacokinetic profile of 1,25-dihydroxyvitamin D2 after administration of Hectorol®.

Study Overview

• Status: Terminated
• Conditions: Secondary Hyperparathyroidism-Chronic Kidney Disease
• Intervention / Treatment: Drug: Doxercalciferol (GZ427397); Drug: Calcitriol

Detailed Description

The total study duration per participant was approximately up to 28 weeks.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 3

Contacts and Locations

Study Locations

• Chile
  • Biobio
    • Concepción, Biobio, Chile, 4070038
      • Investigational Site Number : 1520004
  • Reg Metropolitana de Santiago
    • Santiago, Reg Metropolitana de Santiago, Chile, 7500539
      • Investigational Site Number : 1520003
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's of Alabama- Site Number : 8400022
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center- Site Number : 8400033
    • Sacramento, California, United States, 95817
      • University of California Davis Health- Site Number : 8400005
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine- Site Number : 8400029
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital- Site Number : 8400006
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital - Miami - Southwest 62nd Avenue- Site Number : 8400008
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center- Site Number : 8400020
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • M Health Fairview University of Minnesota Medical Center - West Bank- Site Number : 8400014
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Meridian Health - Hackensack University Medical Center- Site Number : 8400010
    • Morristown, New Jersey, United States, 07962
      • Goryeb Chidlren's Hospital- Site Number : 8400016
  • New York
    • New Hyde Park, New York, United States, 11040
      • Cohen Children's Medical Center- Site Number : 8400017
    • New York, New York, United States, 10029
      • The Mount Sinai Hospital- Site Number : 8400007
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center- Site Number : 8400034
    • Greenville, North Carolina, United States, 27858
      • East Carolina University- Site Number : 8400025
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh- Site Number : 8400028
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Memorial Hospital- Site Number : 8400027
  • Tennessee
    • Nashville, Tennessee, United States, 37292
      • Vanderbilt University Medical Center- Site Number : 8400024
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital- Site Number : 8400013
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Hospital- Site Number : 8400026
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University Medical Center- Site Number : 8400009
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center - Marshfield- Site Number : 8400001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 14 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria :

• Male or female aged 5 to 18 years old.
• Weight ≥15 kg.
• Chronic kidney disease (CKD) Stage 3 or 4 not on dialysis, defined as glomerular filtration rate (GFR) between 15 and 59 mL/min/1.73m^2 (established by Schwartz equation) at Week -2 visit.
• Intact parathyroid hormone (iPTH) value >100 pg/mL for CKD Stage 3 or >160 pg/mL for CKD Stage 4, at Week -2 visit.
• Signed informed consent/assent form.

Exclusion criteria:

• The participant had a serum 25-hydroxyvitamin D level <30 ng/mL at screening.
• The participant had a corrected calcium ≥10 mg/dL at the Week -2 visit.
• The participant had a serum phosphorus >4.5 mg/dL for children 13 to 18 years of age; >5.8 mg/dL for children 5 to 12 years of age at the Week -2 visit.
• The participant was anticipated to require maintenance hemodialysis within 3 months.
• The participant used cinacalcet or vitamin D sterol therapies such as calcitriol, doxercalciferol, or paricalcitol within 14 days prior to the baseline visit.
• The participant had a history of, or active, symptomatic heart disease within 12 months prior to the baseline (Week 0) visit.
• The participant had a chronic gastrointestinal disease (ie, malabsorption, severe chronic diarrhea, chronic ulcerative colitis, or ileostomy).
• The participant had primary hyperparathyroidism or has had a total parathyroidectomy.
• The participant had an active malignancy.
• The participant was unable to swallow a capsule in size similar to the Hectorol® and Rocaltrol® capsules.
• The participant had a history of sensitivity or allergy to doxercalciferol, calcitriol or other vitamin D analogs.
• The participant used aluminum or magnesium-based binders.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hectorol; Hectorol (Doxercalciferol) was administered orally two to three times weekly dependent on participant age. A dose titration scheme was used to individualize the dose to the participant's iPTH management.	Drug: Doxercalciferol (GZ427397); Pharmaceutical form: capsule Route of administration: oral; Other Names: Hectorol
Active Comparator: Rocaltrol; Rocaltrol (Calcitriol) was administered orally seven days/week. A dose titration scheme was used to individualize the dose to the participant's iPTH management.	Drug: Calcitriol; Pharmaceutical form: capsule Route of administration: oral; Other Names: Rocaltrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved 2 Consecutive >=30% Reductions in Intact Parathyroid Hormone From Baseline up to Week 12	Blood samples were collected for assessment of iPTH levels. The percentage of participants meeting the iPTH >=30% reduction from baseline at 2 consecutive study visits up to Week 12 was calculated. Two consecutive >=30% reductions in iPTH from baseline up to Week 12 was defined as two consecutive 30% or greater reductions at any two consecutive measurements from baseline up to Week 12 with on-treatment strategy applied. The confidence interval (CI) was estimated using Clopper-Pearson method. The baseline value is defined as the last available value before the first dose of study treatment. Percentages are rounded off to the tenth decimal place.	Baseline (Day 1) up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Intact Parathyroid Hormone From Baseline to Weeks 12 and 24	Blood samples were collected for assessment of iPTH levels. The percentage changes from baseline iPTH, the effects over the treatment period time was explored using a mixed model for repeated measures approach (MMRM) as appropriate. The baseline value is defined as the last available value before the first dose of study treatment.	Baseline (Day 1) to Weeks 12 and 24
Number of Hypercalcemia Events up to Weeks 12 and 24	Hypercalcemia was defined as albumin corrected serum calcium >10.2 milligrams per deciliter (mg/dL). Here, data for number of hypercalcemia events are reported.	Up to Weeks 12 and 24
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant who was administered a pharmaceutical product, and which did not necessarily have a causal relationship with this treatment. An AE occurred or was detected from the date the participant signed the informed consent form, irrespective of study periods without administration of the study treatment. TEAEs were defined as the AEs that developed, worsened or became serious during the treatment-emergent period (defined as time from administration of study treatment [Day 1] to last administration of study treatment + 4 days). SAE: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.	From first dose of study treatment (Day 1) up to 4 days after the last dose of study treatment; approximately 36 weeks
Maximum Observed Plasma Concentration (Cmax) of 1,25-Dihydroxyvitamin D2 at Week 8 or 10	Blood samples were collected at specified timepoints after administration of doxercalciferol (Hectorol®) to determine Cmax. Evaluation of the 1, 25-Dihydroxyvitamin D2 concentration-time data was obtained using non-compartmental methods. As pre-specified in protocol pharmacokinetic (PK) parameters were assessed at Week 8 or Week 10 choice was as per the schedule availability of the site and the participants.	Pre-dose, 1, 4, 7, and 24 hours post-dose at Week 8 or 10
Time to Maximum Plasma Concentration (Tmax) of 1,25-Dihydroxyvitamin D2 at Week 8 or 10	Blood samples were collected at specified timepoints after administration of doxercalciferol (Hectorol®) to determine tmax. Evaluation of the 1, 25-Dihydroxyvitamin D2 concentration-time data was obtained using non-compartmental methods. As pre-specified in protocol PK parameters were assessed at Week 8 or Week 10 choice was as per the schedule availability of the site and the participants.	Pre-dose, 1, 4, 7, and 24 hours post-dose at Week 8 or 10
Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h) of 1,25-Dihydroxyvitamin D2 at Week 8 or 10	Blood samples were collected at specified timepoints after administration of doxercalciferol (Hectorol®) to determine AUC0-24h. Evaluation of the 1, 25-Dihydroxyvitamin D2 concentration-time data was obtained using non-compartmental methods. As pre-specified in protocol PK parameters were assessed at Week 8 or Week 10 choice was as per the schedule availability of the site and the participants.	Pre-dose, 1, 4, 7, and 24 hours post-dose at Week 8 or 10
Trough Plasma Concentration (Ctrough) of 1,25-Dihydroxyvitamin D2 at Week 8 or 10	Blood samples were collected at specified timepoints after administration of doxercalciferol (Hectorol®) to determine Ctrough. Evaluation of the 1, 25-Dihydroxyvitamin D2 concentration-time data was obtained using non-compartmental methods. As pre-specified in protocol PK parameters were assessed at Week 8 or Week 10 choice was as per the schedule availability of the site and the participants.	Pre-dose, 1, 4, 7, and 24 hours post-dose at Week 8 or 10

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2017
• Primary Completion (Actual): June 11, 2025
• Study Completion (Actual): June 11, 2025

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimated): August 9, 2016

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Neoplastic Processes; Renal Insufficiency; Parathyroid Diseases; Neoplasm Metastasis; Hyperparathyroidism; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary; Lipids; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Hydroxycholecalciferols; Cholecalciferol; Dihydroxycholecalciferols; Calcitriol; 1 alpha-hydroxyergocalciferol
• Other Study ID Numbers: LPS14314; U1111-1178-4657 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No