Safety, Efficacy, PK and PD of CTAP101 (Calcifediol) ER Capsules for SHPT in HD Patients VDI

Chronic Kidney Diseases Clinical Trial

Official title:

A Multi-Center, Randomized, Two-Cohort Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of CTAP101 (Calcifediol) Extended-Release Capsules to Treat Secondary Hyperparathyroidism in Subjects With Vitamin D Insufficiency and Chronic Kidney Disease Requiring Regular Hemodialysis.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03602261
• Other study ID #: CTAP101-CL-2010
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 9, 2018
• Est. completion date: March 31, 2023

Study information

• Verified date: May 2022
• Source: OPKO Health, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Safety, Efficacy, PK and PD of CTAP101 (calcifediol) ER Capsules for SHPT in HD Patients VDI

Description:

A Multi-Center, Randomized, Two-Cohort Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of CTAP101 (calcifediol) Extended-Release Capsules to Treat Secondary Hyperparathyroidism in Subjects with Vitamin D Insufficiency and Chronic Kidney Disease Requiring Regular Hemodialysis.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 256
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Each subject must meet the following criteria to be enrolled into the two cohorts of this

study:

1. Be at least 18 years of age.

2. Be diagnosed with CKD requiring in-center HD tiw for the preceding 6 months, as confirmed by medical history.

3. Be without any disease state or physical condition that might impair evaluation of safety or which, in the investigator's opinion, would interfere with study

participation, including:

1. Serum albumin = 3.0 g/dL; and,

2. Serum transaminase (alanine transaminase [ALT], glutamic pyruvic transaminase [SGPT], aspartate aminotransferase [AST] or glutamic oxaloacetic transaminase [SGOT]) > 2.5 times the upper limit of normal at screening.

4. Be receiving calcimimetic therapy (either etelcalcetide or cinacalcet) and/or calcitriol or other 1a-hydroxylated vitamin D analog (paricalcitol or doxercalciferol) for at least 1 month at the time of screening for enrollment. At least 50% of enrolled subjects will have been receiving calcimimetic therapy.

5. Exhibit during the initial screening visit:

1. Plasma iPTH =150 pg/mL and <600 pg/mL if receiving etelcalcetide, cinacalcet, calcitriol or other 1a-hydroxylated vitamin D analog (paricalcitol or doxercalciferol); or

2. Plasma iPTH =300 pg/mL and <900 pg/mL if not receiving etelcalcetide, cinacalcet, calcitriol or other 1a-hydroxylated vitamin D analog; and,

3. Serum total 25-hydroxyvitamin D <30 ng/mL if not receiving vitamin D supplementation.

6. When otherwise confirmed eligible at Visit 1, must forgo any further treatment with etelcalcetide and cinacalcet for the duration of the study and undergo an 8-week washout period.

7. When otherwise confirmed eligible at Visit 1, must forgo any further treatment with calcitriol or other 1a-hydroxylated vitamin D analogs or vitamin D supplements for the duration of the study and undergo an 8-week washout period.

8. Exhibit after the 8-week washout period (if required due to prior use of etelcalcetide, cinacalcet, calcitriol or other 1a-hydroxylated vitamin D analogs, or vitamin D supplementation):

Cohort 1:

1. Plasma iPTH increased by at least 50%; and,

2. Plasma iPTH =300 pg/mL and <1,200 pg/mL; or, Cohort 2: a. Plasma iPTH =300 pg/mL and <1,200 pg/mL (approximately half of the subjects will be enrolled in each of these two iPTH strata: =300 to <600 and =600 to <1,200 pg/mL); and

Cohorts 1 and 2:

1. Corrected serum calcium <9.8 mg/dL;

2. Serum total 25-hydroxyvitamin D <30 ng/mL; and,

3. Serum phosphorus <6.5 mg/dL.

9. When otherwise confirmed eligible at Visit 1, if taking more than 1,000 mg per day of elemental calcium, reduce calcium use (to =1,000 mg per day) and/or use non-calcium based phosphate binder therapies (as needed) for the duration of the study.

10. When otherwise confirmed eligible at Visit 1, if taking bone metabolism therapies that may interfere with study endpoints, must discontinue use of these agents for the duration of the study.

11. Willing and able to comply with study instructions and commit to all clinic visits for the duration of the study.

12. Female subjects of childbearing potential must be neither pregnant nor lactating and must have a negative serum beta-human chorionic gonadotropin (b-hCG) pregnancy test at the first screening visit and at other scheduled times.

13. All female subjects of childbearing potential and male subjects with female partners of childbearing potential must agree to use effective contraception (eg, implants, injectables, combined oral contraceptives, intrauterine device, sexual abstinence, vasectomy or vasectomized partner) for the duration of the study.

14. Be able to read, understand and sign the subject Informed Consent Form (ICF) or have a legal representative sign the ICF. 4.3 Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from the study:

1. Scheduled kidney transplant or parathyroidectomy.

2. History (prior 2 months) of corrected serum calcium =9.8 mg/dL or serum phosphorus =6.5 mg/dL if not receiving calcitriol or other 1a-hydroxylated vitamin D analog.

3. Receipt of bisphosphonate therapy or other bone modifying treatment (eg, denosumab) within 6 months prior to enrollment.

4. Known previous or concomitant serious illness or medical condition, such as malignancy, human immunodeficiency virus, significant gastrointestinal or hepatic disease, intestinal malabsorption disorder, hepatitis or cardiovascular event that in the opinion of the investigator may worsen or reduce life expectancy, and/or interfere with participation in the study.

5. History of neurological/psychiatric disorder, including psychotic disorder or dementia, or any reason which, in the opinion of the investigator makes adherence to a treatment or follow-up schedule unlikely.

6. Known or suspected hypersensitivity to any of the constituents of the study drugs.

7. Currently participating in, or has participated in, an interventional/investigational study within 30 days prior to study screening.

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Hyperparathyroidism
• Hyperparathyroidism, Secondary
• Kidney Diseases
• Neoplasm Metastasis
• Renal Insufficiency, Chronic
• Secondary Hyperparathyroidism Due to Renal Causes
• Stage 5 Chronic Kidney Disease
• Vitamin D Deficiency

Intervention

Drug:
• Calcifediol Oral Capsule
Capsule, weekly
• Placebo oral capsule
Capsule, weekly

Locations

Country	Name	City	State
United States	University of Colorado Denver Anschutz Medical Campus	Aurora	Colorado
United States	Research by Design, LLC	Chicago	Illinois
United States	WCCT Global, Inc.	Cypress	California
United States	Northshore University Health	Evanston	Illinois
United States	Hacienda Dialysis Center	Hacienda Heights	California
United States	Southwest Houston Research LTD	Houston	Texas
United States	California Institute of Renal Research CKD/Dialysis & Transplant Division	La Mesa	California
United States	Long Beach Quest Dialysis Center	Long Beach	California
United States	Southwest MS Nephrology	McComb	Mississippi
United States	Ontario Dialysis Center	Ontario	California
United States	AKDHC Medical Research Services	Peoria	Arizona
United States	AKDHC Medical Research Services	Phoenix	Arizona
United States	AKDHC Medical Research Services	Phoenix	Arizona
United States	AKDHC Medical Research Services	Phoenix	Arizona
United States	Kidney & Hypertension Specialists	San Antonio	Texas
United States	North America Research Institute, Inc.	San Dimas	California
United States	Renal and Transplant Associates of New England	Springfield	Massachusetts
United States	Laurel Canyon Dialysis, LLC	Sun Valley	California

Sponsors (1)

Lead Sponsor	Collaborator
OPKO Health, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of mean plasma intact parathyroid hormone (iPTH)	Change of at least 30% from pre-treatment baseline	26 weeks
Primary	Severity of Treatment-Emergent Adverse Events as assessed by CTCAE version 5.0	Detailed information collected for each TEAE will include: AE number, a description of the event, start date, end date or ongoing as of date, outcome, therapy for event	32 weeks
Primary	Maximum Plasma Concentration [Cmax]	Maximum serum concentration of Calcifediol	74 weeks
Primary	Increase mean serum total 25-hydroxyvitamin D	Increase to =30 ng/mL	26 weeks