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NPSP558

Phase 3

Hypoparathyroidism | Small molecule | Endocrine |Takeda Pharmaceutical Company Limited|Last Updated: Jun 11, 2021

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials4
Total Enrollment241
FDA Designations
No designations recorded
Clinical Trials (4)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01455181A Study to Investigate the Safety and Tolerability of NPSP558, for the Treatment of Adults With Hypoparathyroidism - A Clinical Extension Study in HungaryPHASE3 COMPLETED 24Aug 19, 2011Apr 26, 2012Jun 11, 20213 Hungary
NCT01297309A 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)PHASE3 COMPLETED 51Apr 6, 2011Jun 8, 2018May 25, 202114 United States
NCT01268098Study of Safety and Efficacy of a rhPTH[1-84] of Fixed Doses of 25 and 50 mcg in Adults With Hypoparathyroidism (RELAY)PHASE3 COMPLETED 42Feb 9, 2011Nov 11, 2011Jun 11, 202112 United States
NCT00732615Use of NPSP558 in the Treatment of HypoparathyroidismPHASE3 COMPLETED 124Dec 18, 2008Sep 28, 2011Jun 3, 202131 United States, Belgium +6
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Study Endpoints
Primary Endpoints
Percentage of Subjects Who Achieved the Primary Triple Endpoint at Week 24, Based on Investigator Prescribed Data.
24 Weeks

A ≥ 50% reduction from baseline in dose of oral calcium or an oral calcium dose of ≤ 500 mg and a ≥ 50% reduction from baseline in dose of oral active vitamin D (calcitriol dose of ≤ 0.25 μg/day or alphacalcidol dose of ≤ 0.50 μg/day) and a total serum calcium concentration that was normalized or maintained compared to the baseline value and did not exceed the ULN of the central laboratory.

Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE)
From start of study drug administration up to follow-up (82 months)

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.

Number of Responders With Calcium Source at Week 52
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.

Number of Responders With Calcium Source at End Of Treatment (EOT) (Up to 82 Months)
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.

Percentage of Subjects Who Achieved the Primary Triple Endpoint at Week 8, Based on Investigator Prescribed Data.
8 Weeks

The triple efficacy endpoint criteria were defined as a reduction from baseline in oral calcium to ≤ 500 mg/day, a reduction from baseline in calcitriol dose to ≤ 0.25 µg/day, and an albumin-corrected total serum calcium level between 7.5 mg/dL and the upper limit of the laboratory normal range. The analysis of primary endpoint was based on investigator prescribed data.

The Percentage of Subjects Who Met the Triple Efficacy Endpoint Criteria at Week 24.
Week 24 of dosing

The triple efficacy endpoint criteria were defined as at least a 50% reduction from the baseline in oral calcium dose and at least a 50% reduction from the baseline in active vitamin D dose and an albumin-corrected total serum calcium concentration that was maintained or normalized compared to the baseline value (≥ 7.5 mg/dL) and did not exceed the upper limit of the laboratory normal range. The analysis of primary efficacy endpoint was based on investigator prescribed data.

Secondary Endpoints
Mean Percentage Changes From Baseline in Active Vitamin D Dosages at Each Visit
24 Weeks
Mean Percentage Changes From Baseline in Oral Calcium at Each Visit
24 Weeks
Proportion of Patients Achieving the Primary Endpoint at Each Visit
24 Weeks
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
NPSP558EXPERIMENTAL -
25 µg doseEXPERIMENTAL25 µg
50 µg doseEXPERIMENTAL50 µg
PlaceboPLACEBO_COMPARATORSterile water for injection
50, 75, 100 mcg NPSP558EXPERIMENTALInitial dose of 50mcg, to be titrated up to 75mcg and then 100mcg dependent upon response
Interventions
NameTypeDescription
NPSP558DRUG50, 75, 100 μg
PlaceboDRUGPlacebo for subcutaneous injection
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Eligibility Criteria
Age Range18 Years — 85 Years
SexALL
Healthy VolunteersNo
Study Sites3

Inclusion Criteria: Patients who meet all the following inclusion criteria can be enrolled into this study: 1. Signed and dated informed consent form (ICF) before any study-related procedures are performed 2. Previously completed 24 weeks of therapy and 4 weeks of follow-up in the REPLACE study, O...

Countries:HungaryUnited StatesBelgiumCanadaDenmarkFranceItalyUnited Kingdom
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