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)

• ClinicalTrials.gov Identifier: NCT01297309
• Recruitment Status: Completed
• First Posted: February 16, 2011
• Results First Posted: August 6, 2019
• Last Update Posted: May 25, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

Tracking Information

• First Submitted Date: February 11, 2011
• First Posted Date: February 16, 2011
• Results First Submitted Date: June 7, 2019
• Results First Posted Date: August 6, 2019
• Last Update Posted Date: May 25, 2021
• Actual Study Start Date: April 6, 2011
• Actual Primary Completion Date: June 8, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 16, 2019)

• Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: February 14, 2011)

• A reduction in oral calcium or an oral calcium dose of ≤ 500 mg [ Time Frame: 52 weeks of treatment, 4 weeks of follow-up ]
• A reduction in oral calcitriol to ≤ 0.25 μg [ Time Frame: 52 weeks of treatment, 4 weeks of follow-up ]
• An albumin-corrected total serum calcium concentration that is normalized or maintained compared to the baseline value (≥7.5 mg/dL) and ULN [ Time Frame: 52 weeks of treatment, 4 weeks of follow-up ]

Current Secondary Outcome Measures (submitted: July 16, 2019)

• Percent Change From Baseline in Oral Calcium Supplementation at Week 52 and EOT (Up to 82 Months) [ Time Frame: Baseline, 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.
• Percent Change From Baseline in Oral Calcitriol Supplementation at Week 52 and EOT (Up to 82 Months) [ Time Frame: Baseline, 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.
• Percent Change From Baseline in Albumin Corrected Total Serum Calcium (ACSC) at EOT (Up to 82 Months) [ Time Frame: Baseline, 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.
• Change From Baseline in 24-Hour Urine Calcium Excretion Through EOT (Up to 82 Months) [ Time Frame: Baseline, 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.
• Change From Baseline in 24-hour Urine Calcium Excretion in Participants Who Used Calcium-Sparing Diuretics Through EOT (Up to 82 Months) [ Time Frame: Baseline, 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.
• Change From Baseline in Serum Calcium Concentration in Participants Who Used and Calcium Sparing Diuretics at EOT (Upto 82 Months) [ Time Frame: Baseline, 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.
• Change From Baseline in Serum Phosphate at Month 72 and EOT (Upto 82 Months) [ Time Frame: Baseline, Month 72, 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.
• Number of Participants Who Maintained a Calcium Phosphate Product in A Normal Range at EOT (Up to 82 Months) [ Time Frame: 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).
• Change From Baseline in Bone Turnover Markers at EOT (Up to 82 Months) [ Time Frame: Baseline, 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.
• Change From Baseline in Serum Carboxy Terminal Telopeptide of Type I Collagen (s-CTx) Bone Turnover Marker at EOT (Up to 82 Months) [ Time Frame: Baseline, 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.
• Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months) [ Time Frame: Baseline, 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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: 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)
• Brief Summary: This study is a long-term, open-label study using NPSP558 for the treatment of adult patients with Hypoparathyroidism.
• Detailed Description: 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hypoparathyroidism

Intervention

Drug: NPSP558

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.

Other Name: RACE

Study Arms

Experimental: NPSP558

titration of 25, 50, 75 or 100 μg

Intervention: Drug: NPSP558

Publications *

• Ayodele O, Mu F, Berman R, Swallow E, Rejnmark L, Gosmanova EO, Kaul S. Lower Risk of Cardiovascular Events in Adult Patients with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study. Adv Ther. 2022 Aug;39(8):3845-3856. doi: 10.1007/s12325-022-02198-y. Epub 2022 Jun 11.
• Chen KS, Gosmanova EO, Curhan GC, Ketteler M, Rubin M, Swallow E, Zhao J, Wang J, Sherry N, Krasner A, Bilezikian JP. Five-year Estimated Glomerular Filtration Rate in Patients With Hypoparathyroidism Treated With and Without rhPTH(1-84). J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3557-65. doi: 10.1210/clinem/dgaa490.
• Mannstadt M, Clarke BL, Bilezikian JP, Bone H, Denham D, Levine MA, Peacock M, Rothman J, Shoback DM, Warren ML, Watts NB, Lee HM, Sherry N, Vokes TJ. Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5136-5147. doi: 10.1210/jc.2019-01010.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 16, 2019): 51
• Original Estimated Enrollment (submitted: February 14, 2011): 40
• Actual Study Completion Date: June 8, 2018
• Actual Primary Completion Date: June 8, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01297309
• Other Study ID Numbers: PAR-C10-008
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• URL: https://vivli.org/ourmember/takeda/

• Current Responsible Party: Takeda ( Shire )
• Original Responsible Party: NPS Pharmaceuticals
• Current Study Sponsor: Shire
• Original Study Sponsor: NPS Pharma
• Collaborators: Not Provided

Investigators

• Study Director: Study Director; Takeda

• PRS Account: Takeda
• Verification Date: May 2021