Phase 3 Safety and Efficacy Study of CTAP101 Extended-release Capsules in Children With Secondary Hyperparathyroidism

A Multi-Center Study to Evaluate the Efficacy, Safety and Pharmacokinetics of CTAP101 Extended-release Capsules to Treat Secondary Hyperparathyroidism in Pediatric Subjects of Ages 8 to <18 Years With Stage 3 or 4 Chronic Kidney Disease and Vitamin D Insufficiency

This is a phase 3, multi-center, randomized, double-blind, placebo-controlled study in children with stage 3-4 chronic kidney disease (CKD), secondary hyperparathyroidism (SHPT) and vitamin D insufficiency.

Inclusion Criteria:

1. Cohort 1: Be 12 to <18 years of age and have a body weight of ≥40 kg; Cohort 2: be 8 to <12 years of age and have a body weight of ≥20 kg.

2. Be diagnosed with stage 3 to 4 CKD at least six months prior to the screening visit, and have an eGFR of ≥15 to <60 mL/min/1.73m2 at screening.

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;
   2. Serum transaminase (ALT or SGPT, AST or SGOT) > 2.5 times the upper limit of normal at screening; and,
   3. Urinary albumin excretion of >3000 mcg/mg creatinine.

4. Exhibit during the initial or, if necessary, a screening visit after washout:

   1. Plasma iPTH >100 pg/mL (stage 3 CKD) or >160 pg/mL (stage 4 CKD)
   2. Serum calcium <9.8 mg/dL (corrected for albumin);
   3. Serum total 25-hydroxyvitamin D <30 ng/mL; and,
   4. Serum phosphorus >2.5 to ≤5.5 mg/dL (12 to <18 years) or ≤6.0 mg/dL (ages 8 to <12 years).

5. If taking calcitriol or other 1α-hydroxylated vitamin D analogs, or cinacalcet, be willing to forgo treatment with these agents for the duration of the study and complete an 8-week washout period prior to commencing treatment in the study.

6. If taking >1,000 mg/day of elemental calcium, discontinue or reduce calcium use and/or use non-calcium based therapies for the duration of the study.

7. If receiving ≤1,700 IU/day nutritional vitamin D (ergocalciferol or cholecalciferol) therapy, must agree to remain on a stable dose during the study.

8. If taking >1,700 IU/day of nutritional vitamin D, must discontinue or decrease the dose to ≤1,700 IU/day, maintain that dose for the duration of the study, and complete an 8-week washout period prior to commencing treatment in the study provided that serum total 25-hydroxyvitamin D is ≥30 ng/mL. The washout period is not necessary if serum total 25-hydroxyvitamin D is <30 ng/mL.

9. If taking any bone modifying treatment that could interfere with study endpoints, must discontinue use of such agent(s) for the duration of the study.

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

11. Female subjects of childbearing potential must be neither pregnant nor lactating and must have a negative urine pregnancy test at the first screening visit.

12. 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.

13. Each subject or their legal representative must be able to read, understand and sign the informed consent form (ICF).

Exclusion Criteria:

1. History of or planned kidney transplant or parathyroidectomy.
2. History (prior three months) of serum calcium ≥9.8 mg/dL.
3. Use of bisphosphonate therapy (denosumab) within six 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 or cardiovascular event or hepatitis, or physical condition that in the opinion of the investigator may worsen and/or interfere with participation in the study.
5. History of neurological/psychiatric disorder, including psychotic disorder, 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 either investigational product.
7. Currently participating in, or has participated in, an interventional/investigational study within 30 days prior to study screening.