A Open-label Study Investigating the Safety and Tolerability of NPSP558, a Recombinant Human Parathyroid Hormone (rhPTH [1-84]), for the Treatment of Adults With Hypoparathyroidism - A Clinical Extension Study (RACE)

Study Overview
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Brief Summary
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This study is a long-term, open-label study using NPSP558 for the treatment of adult patients with Hypoparathyroidism.

Detailed Description
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Patients with a history of Hypoparathyroidism will be enrolled to receive study drug for up to 80 months, which will be injected daily in either thigh. During that time they will be monitored for safety (specifically calcium levels in blood or urine). In addition, the patients' intake of Vitamin D and Calcium will be measured.

Official Title
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A Long-term Open-label Study Investigating the Safety and Tolerability of NPSP558, a Recombinant Human Parathyroid Hormone (rhPTH[1-84]), for the Treatment of Adults With Hypoparathyroidism - A Clinical Extension Study (RACE)

Conditions
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Hypoparathyroidism

Intervention / Treatment
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* Drug: NPSP558


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously completed the rhPTH[1-84] RELAY study (8 weeks of active therapy) and/or previously completed the rhPTH[1-84] REPLACE study (Visit 18). Able to perform daily SC self-injections of study medication (or have a designee perform injection). Women who are (1) postmenopausal; (2) surgically sterilized; or, (3) of childbearing potential with a negative pregnancy test and who consent to use two acceptable methods of contraception for the duration of the study. Males who have female partners of childbearing potential must use two acceptable forms of contraception for the duration of the study. Serum creatinine <1.5 mg/dL at enrollment. Total serum calcium less than or equal to upper limit of normal (ULN) based on local laboratory result prior to enrollment. Serum 25 hydroxy (OH) vitamin D less than or equal to 1.5 times the ULN within approximately 16 weeks prior to enrollment. Exclusion Criteria: Any condition that, in the investigator's opinion after consultation with the sponsor, would preclude the safe use of parathyroid hormone (PTH). Pregnant or lactating women. Any disease or condition which has a high probability of precluding the subject from completing the study or where the subject cannot or will not appropriately comply with study requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NPSP558<br>titration of 25, 50, 75 or 100 μg | Drug: NPSP558<br>* All patients will inject NPSP558 individual titration of 25, 50, 75 or 100 μg SC QD into alternating thighs in the morning via a multidose injection pen device.<br>* Other names: RACE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) | SAE is an adverse event (AE) that results in death, life threatening, persistent or significant incapacity or substantial disruption of ability to conduct normal life functions, hospitalization or prolongation of existing hospitalization, congenital anomaly or birth defect, important medical events that may not result in death, be life threatening, or require hospitalization. An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical or medicinal product. Treatment emergent adverse events (TEAEs) were defined as AEs whose onset occurs, severity worsens or intensity increases after receiving the study medication of this study and <= 30 days after last dose of study drug. | From start of study drug administration up to follow-up (82 months) | 
| Number of Responders With Calcium Source at Week 52 | A responder was defined as a participant who met all of the following 3 criteria at each (1) a greater than (>) 50% reduction from baseline or less than (<) 500 milligram (mg) of daily calcium supplementation. (2) a >50% reduction from baseline or <0.25 microgram (mcg) of daily calcitriol supplementation. (3) an albumin-corrected total serum calcium concentration that was normalized or maintained compared to the baseline greater than or equal to (>=) 1.875 millimoles per liter (mmol/L) and not exceeding the Upper Limit of Normal (ULN) values (2.15 to 2.55 mmol/L). End of Treatment (EOT) was defined as the last determination of response or last available measurement during the treatment period. Number of responders with calcium source for citrate and carbonate at week 52 was reported here. | Week 52 | 
| Number of Responders With Calcium Source at End Of Treatment (EOT) (Up to 82 Months) | A responder was defined as a participant who met all of the following 3 criteria at each (1) a greater than (>) 50% reduction from baseline or less than (<) 500 milligram (mg) of daily calcium supplementation. (2) a >50% reduction from baseline or <0.25 microgram (mcg) of daily calcitriol supplementation. (3) an albumin-corrected total serum calcium concentration that was normalized or maintained compared to the baseline greater than or equal to (>=) 1.875 millimoles per liter (mmol/L) and not exceeding the Upper Limit of Normal (ULN) values (2.15 to 2.55 mmol/L). End of Treatment (EOT) was defined as the last determination of response or last available measurement during the treatment period. Number of responders with calcium source for citrate and carbonate at EOT was reported here. | EOT (up to 82 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Oral Calcium Supplementation at Week 52 and EOT (Up to 82 Months) | Percent change from baseline of oral calcium supplementation were reported. EOT was defined as the last determination of response or last available measurement during the treatment period. | Baseline, Week 52 and EOT (up to 82 months) | 
| Percent Change From Baseline in Oral Calcitriol Supplementation at Week 52 and EOT (Up to 82 Months) | Percent change from baseline of oral calcitriol supplementation were reported. EOT was defined as the last determination of response or last available measurement during the treatment period. | Baseline, Week 52 and EOT (up to 82 months) | 
| Percent Change From Baseline in Albumin Corrected Total Serum Calcium (ACSC) at EOT (Up to 82 Months) | Percent change in ACSC was reported. EOT was defined as the last determination of response or last available measurement during the treatment period. | Baseline, EOT (up to 82 months) | 
| Change From Baseline in 24-Hour Urine Calcium Excretion Through EOT (Up to 82 Months) | Change in 24 hour urine calcium excretion was reported. EOT was defined as the last determination of response or last available measurement during the treatment period. | Baseline, EOT (up to 82 months) | 
| Change From Baseline in 24-hour Urine Calcium Excretion in Participants Who Used Calcium-Sparing Diuretics Through EOT (Up to 82 Months) | Change from baseline in urinary calcium concentration in participants who used at least one calcium-sparing diuretics and participants who not used calcium-sparing diuretics were reported. EOT was defined as the last determination of response or last available measurement during the treatment period. | Baseline, EOT (up to 82 months) | 
| Change From Baseline in Serum Calcium Concentration in Participants Who Used and Calcium Sparing Diuretics at EOT (Upto 82 Months) | Change in serum calcium concentration of the number of participants who used at least one calcium-sparing diuretics and not used calcium sparing diuretics were reported. EOT was defined as the last determination of response or last available measurement during the treatment period. | Baseline, EOT (upto 82 months) | 
| Change From Baseline in Serum Phosphate at Month 72 and EOT (Upto 82 Months) | Change of serum phosphate from baseline were reported. EOT was defined as the last determination of response or last available measurement during the treatment period. | Baseline, Month 72, EOT (upto 82 months) | 
| Number of Participants Who Maintained a Calcium Phosphate Product in A Normal Range at EOT (Up to 82 Months) | The normal range of calcium phosphate product is defined as <= 4.441 millimoles square per liter square (mmol^2/L^2). | EOT (up to 82 months) | 
| Change From Baseline in Bone Turnover Markers at EOT (Up to 82 Months) | Bone Turnover Markers such as bone specific alkaline phosphatase (BSAP), serum procollagen type 1 amino-terminal propeptide (P1NP) , osteocalcin were reported in particpiants. EOT was defined as the last determination of response or last available measurement during the treatment period. | Baseline, EOT (up to 82 months) | 
| Change From Baseline in Serum Carboxy Terminal Telopeptide of Type I Collagen (s-CTx) Bone Turnover Marker at EOT (Up to 82 Months) | Change form baseline in bone turnover marker (s-CTx)was reported. EOT was defined as the last determination of response or last available measurement during the treatment period. | Baseline, EOT (up to 82 months) | 
| Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) | Change from baseline in BMD of lumbar spine (L1-L4), hip-total, hip-trochanter, hip-intertrochanter, hip-ward's triangle, hip-femoral neck, distal one third radius at Week 52 then every 12 months until EOT were assessed by dual-energy X-ray absorptiometry [DXA] and Z-score. EOT was defined as the last determination of response or last available measurement during the treatment period. | Baseline, Week 52 and EOT (up to 82 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTH 1-84, Hypoparathyroidism, Parathyroid Hormone 1-84, NPSP558