Clinical trial NCT05460234: RAYALDEE Non Interventional Study (NIS) on Effectiveness in ND-CKD SHPT Patients
Official title: Non-interventional Study to Collect Real-world Effectiveness, Safety, and Adherence Data on Extended-release Calcifediol (Rayaldee®) in Non-dialysis CKD Patients With Secondary Hyperparathyroidism. Protocol Version 2.0, 06DEC2023
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Chronic Kidney Disease
Keywords: hyperparathyroidism
calcifediol
Lead sponsor: Vifor Pharma
Sponsor class: INDUSTRY
First posted: 2022-07-15
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will enrol patients from approximately 18 sites in Germany. Male or female adult patients with a diagnosis of ND-CKD and SHPT who are due to be treated with ERC according to their physicians usual standard of care and in accordance with the SMPC are eligible.

Brief summary: The overall study objective is to collect real-world data on the safety and effectiveness of ERC to gradually increase 25D to the level required by Stage 3 and 4 CKD patients.

ERC (Rayaldee), a prolonged-release calcifediol (PRC) formulation, is an orally administered prohormone of active Vitamin D (1,25-dihydroxyvitamin D (1,25D)) designed to increase serum total 25D safely and to a high enough magnitude to reliably reduce elevated PTH in patients with non-dialysis chronic kidney disease (ND-CKD). Clinical studies show that ERC is an effective, well tolerated treatment for secondary hyperparathyroidism (SHPT) in ND-CKD patients with Vitamin D insufficiency or deficiency. ERC gradually raises serum 25D levels, resulting in physiologically regulated increases in serum 1,25D and sustained and progressive reductions in PTH levels, while avoiding clinically meaningful increases in serum phosphate and calcium.

To date, experience with the use of ERC results exclusively from patients from the US and mainly from patients who have participated in clinical trials. It is therefore of major interest to observe the value of ERC in daily use outside of the controlled trial settings in the US as well as in Europe. (Protocol v.2.0,06Dec2023).

Detailed description: Non-interventional, prospective, multicentre, cohort study. Approximately 100 patients diagnosed with ND-CKD with SHPT being treated with ERC according to the SmPC will be included.

The scheduled total study duration is 2.5 years, with a recruitment phase of approximately 1.5 years. The individual prospective observational period per patient is scheduled to last up to 12 months, or up to 18 months for pre-treated patients. The number of observational time points for an individual patient will be dependent on the individual observational period and is assumed to be approximately every 3 months.

A patient is eligible if ERC treatment initiation can coincide with the date of patient inclusion in the study or can happen up to 6 months before patient inclusion in the study. The observational period of ERC treatment will be retrospective if it occurs before study inclusion and prospective for the period after study inclusion. The decision to initiate treatment remains with the treating physician, in line with their normal standard of care, in accordance with the SMPC.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent

  * Age ≥18 years
  * Indication for ERC treatment in accordance with the currently approved SmPC.
  * Starting ERC treatment or being on ERC treatment for a maximum of 6 months before inclusion in the study.
  * Stable kidney function in the medical judgment of the investigator

Exclusion Criteria:

Parallel participation in an interventional study

• Enrolment in a prior clinical trial with ERC

Primary outcomes:
measure: Change in 25-hydroxyvitamin D (25D) and iPTH levels
timeFrame: From up to 6 months prior of ERC treatment start to up to 18 months after treatment
measure: Change in serum calcium level
timeFrame: From up to 6 months prior of ERC treatment start to up to 18 months after treatment
measure: Change in serum phosphate level
timeFrame: From up to 6 months prior of ERC treatment start to up to 18 months after treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Dialysepraxis Spandau - 01012
city: Berlin
country: Germany
facility: Tagesklinik - Lehrpraxis der Charité Dialyse - Apherese -01007
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig gGmbH -01006
city: Eichstätt
country: Germany
facility: Nierenzentrum Eichstätt MVZ GmbH - 01072
city: Greifswald
country: Germany
facility: Universitätsklinik Greifswald Klinik und Poliklinik für Innere Medizin A -01066
city: Herne
country: Germany
facility: Marien Hospital Herne-Uniklinikum - 01003
city: Homburg
country: Germany
facility: MVZ Saarpfalz GmbH - 01008
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH - 01025
city: Kulmbach
country: Germany
facility: Nephrologische Gemeinschaftspraxis Baumhackl & Rasche - 01028
city: Landshut
country: Germany
facility: Klinikum Landshut -01002
city: Mainz
country: Germany
facility: Universitätsklinikum Mainz - 01004
city: Münster
country: Germany
facility: Uniklinik Münster, Nephrologische Ambulanz - 01018
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Medizinische Klinik D - 01073
city: Rendsburg
country: Germany
facility: Nephrologisches Zentrum Rendsburg-Eckernförde - 01056
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus - 01001
city: Witten
country: Germany
facility: Gim - 01013
Study officials:
affiliation: Robert Bosch Gesellschaft für Medizinische Forschung mbH
name: Markus Ketteler, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Petkovich M, Melnick J, White J, Tabash S, Strugnell S, Bishop CW. Modified-release oral calcifediol corrects vitamin D insufficiency with minimal CYP24A1 upregulation. J Steroid Biochem Mol Biol. 2015 Apr;148:283-9. doi: 10.1016/j.jsbmb.2014.11.022. Epub 2014 Nov 22.
citation: Sprague SM, Silva AL, Al-Saghir F, Damle R, Tabash SP, Petkovich M, Messner EJ, White JA, Melnick JZ, Bishop CW. Modified-release calcifediol effectively controls secondary hyperparathyroidism associated with vitamin D insufficiency in chronic kidney disease. Am J Nephrol. 2014;40(6):535-45. doi: 10.1159/000369939. Epub 2015 Jan 7.
citation: Sprague SM, Crawford PW, Melnick JZ, Strugnell SA, Ali S, Mangoo-Karim R, Lee S, Petkovich PM, Bishop CW. Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease. Am J Nephrol. 2016;44(4):316-325. doi: 10.1159/000450766. Epub 2016 Sep 28.
citation: Sprague SM, Strugnell SA, Bishop CW. Extended-release calcifediol for secondary hyperparathyroidism in stage 3-4 chronic kidney disease. Expert Rev Endocrinol Metab. 2017 Sep;12(5):289-301. doi: 10.1080/17446651.2017.1347501. Epub 2017 Jul 11.
citation: Strugnell SA, Sprague SM, Ashfaq A, Petkovich M, Bishop CW. Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease. Am J Nephrol. 2019;49(4):284-293. doi: 10.1159/000499187. Epub 2019 Mar 15.
citation: Cozzolino M, Ketteler M. Evaluating extended-release calcifediol as a treatment option for chronic kidney disease-mineral and bone disorder (CKD-MBD). Expert Opin Pharmacother. 2019 Dec;20(17):2081-2093. doi: 10.1080/14656566.2019.1663826. Epub 2019 Nov 1.
citation: Ketteler M, Ambuhl P. Where are we now? Emerging opportunities and challenges in the management of secondary hyperparathyroidism in patients with non-dialysis chronic kidney disease. J Nephrol. 2021 Oct;34(5):1405-1418. doi: 10.1007/s40620-021-01082-2. Epub 2021 Jun 25.
citation: Cozzolino M, Minghetti P, Navarra P. Extended-release calcifediol in stage 3-4 chronic kidney disease: a new therapy for the treatment of secondary hyperparathyroidism associated with hypovitaminosis D. J Nephrol. 2022 Apr;35(3):863-873. doi: 10.1007/s40620-021-01152-5. Epub 2021 Oct 9.
citation: Fadda G, Germain MJ, Broumand V, Nguyen A, McGarvey N, Gitlin M, Bishop CW, Ashfaq A. Real-World Assessment: Clinical Effectiveness and Safety of Extended-Release Calcifediol. Am J Nephrol. 2021;52(10-11):798-807. doi: 10.1159/000518545. Epub 2021 Oct 27.