Safety and Efficacy of CTAP101 to Treat Secondary Hyperparathyroidism in Stage 3 or 4 CKD and Vitamin D Insufficiency

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the efficacy of CTAP101 Capsules versus placebo in reducing intact parathyroid hormone (iPTH) by at least 30% from pretreatment baseline; safety and tolerability of CTAP101 will also be evaluated

Detailed Description
-----------------
This is a phase 3, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of CTAP101 Capsules administered for 26 weeks to treat SHPT in subjects ≥18 years of age with stage 3 or 4 CKD and vitamin D insufficiency. The study will be conducted at approximately 40 sites within the United States (US). Approximately 550 subjects will be screened to randomize approximately 210 eligible subjects, stratified by CKD stage (approximately 105 subjects in each stage) in a 2:1 ratio to receive either CTAP101 Capsules or matching placebo. An Interactive Voice Response System (IVRS) will provide study treatment group assignments using the computer-generated randomization code provided by the IVRS vendor. Subjects will receive an initial daily dose of 1 capsule (CTAP101 Capsules, 30 µg, or matching placebo) for the first 12 weeks. After l2 weeks (visit 8) and per pre-defined criteria, the dose may be increased in a blinded fashion by the IVRS with oversight by an independent medical monitor.

Official Title
-----------------
A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of CTAP101 Capsules to Treat Secondary Hyperparathyroidism in Subjects With Stage 3 or 4 Chronic Kidney Disease and Vitamin D Insufficiency

Conditions
-----------------
Chronic Kidney Disease, Hyperparathyroidism, Secondary, Vitamin D Deficiency

Intervention / Treatment
-----------------
* Drug: CTAP101 30 μg capsules
* Other: Sugar pill to CTAP101 30 μg capsules


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Urinary albumin excretion ≤ 3000 mcg/mg of creatinine Stage 3 or 4 CKD Plasma iPTH: ≥ 85 pg/mL and < 500 pg/mL Serum Ca: ≥ 8.4 mg/dL and < 9.8 mg/dL Serum P: ≥ 2.0 mg/dL and < 5.0 mg/dL Serum 25-hydroxyvitamin D: ≥ 10 ng/mL and < 30 ng/mL. Stable dose of Vitamin D therapy ≤ 1600 IU/day and receiving same dose for at least 2 months Exclusion Criteria: History of kidney transplant or parathyroidectomy Spot urine calcium:creatinine ratio > 0.2 (>200 mg/g Cr) Current serious illness, such as malignancy, HIV, liver disease, cardiovascular event or hepatitis Currently on dialysis Use of pharmacological dose of ergocalciferol or cholecalciferol (≥ 50,000 IU mcg per month) during the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CTAP101 30 μg capsules<br>1 CTAP101 30 μg capsule daily at bedtime for 12 weeks, with a possible increase to 2 CTAP101 30 μg capsules daily at bedtime for study duration, if needed (26 weeks total). Subjects not requiring a dose increase after 12 weeks would receive 1 CTAP101 30 μg capsule and one sugar pill (to CTAP101 30 μg capsule) for weeks 13-26. | Drug: CTAP101 30 μg capsules<br>* CTAP101 30 μg capsule taken daily at bedtime<br>* Other names: Calcifediol;Other: Sugar pill to CTAP101 30 μg capsules<br>* Sugar pill capsule (placebo to CTAP101 30 μg capsule) taken daily at bedtime.<br>* Other names: Placebo;|
| Placebo Comparator: Sugar pill to CTAP101 30 μg<br>1 sugar pill to CTAP101 30 μg capsule daily at bedtime for 12 weeks, with an increase to 2 sugar pills to CTAP101 30 μg capsules daily at bedtime for weeks 13-26. | Other: Sugar pill to CTAP101 30 μg capsules<br>* Sugar pill capsule (placebo to CTAP101 30 μg capsule) taken daily at bedtime.<br>* Other names: Placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants in the Intent to Treat Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline | Number of subjects in the intent to treat population attaining mean decrease in plasma intact Parathyroid Hormone (iPTH) of ≥30% from P\pre-treatment baseline in the efficacy assessment phase (EAP) referred to as responders | Approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants in the Per Protocol Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline | Number of subjects in the per protocol population attaining a mean decrease in plasma intact parathyroid hormone (iPTH) of ≥30% from pre-treatment baseline in the efficacy assessment phase (EAP), referred to as responders | Approximately 6 months | 
| Subjects in the Intent to Treat Population With Normal Serum Total 25-hydroxyvitamin D | Subjects in the intent to treat population with normal serum total 25-hydroxyvitamin D (>/= 30 ng/dL) | Approximately 6 months | 
| Subjects in the Per Protocol Population With Normal Serum Total 25-hydroxyvitamin D | Subjects in the per protocol population with normal serum total 25-hydroxyvitamin D (>/= 30 ng/mL) | Approximately 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vitamin D, Parathyroid Diseases, Renal Insufficiency, Kidney Failure, Chronic, Hyperparathyroidism, Secondary, Hyperparathyroidism, Kidney Diseases, Kidney Failure, Renal Insufficiency, Chronic