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)

NCT01297309 | Completed Phase 3 Results

• 1 other identifier: PAR-C10-008
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 14

Brief Summary

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

Conditions

Hypoparathyroidism

Keywords

PTH 1-84; Hypoparathyroidism; Parathyroid Hormone 1-84; NPSP558

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (11)

• Percent Change From Baseline in Oral Calcium Supplementation at Week 52 and EOT (Up to 82 Months)

  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)

  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)

  Baseline, EOT (up to 82 months)

• Change From Baseline in 24-Hour Urine Calcium Excretion Through EOT (Up to 82 Months)

  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)

  Baseline, EOT (up to 82 months)

Study Arms (1)

NPSP558

EXPERIMENTAL

titration of 25, 50, 75 or 100 μg

Drug: NPSP558

Interventions

NPSP558 DRUG

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.

Also known as: RACE

NPSP558

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (14)

Advance Medical Research LLC

Lakewood, California, 90712, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Michigan Bone & Mineral Clinic PC

Detroit, Michigan, 48236, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University Physicians Group

Staten Island, New York, 10301, United States

Location

Physician East PA

Greenville, North Carolina, 27834, United States

Location

University of Cincinnati Bone Health and Osteoporosis Center

Cincinnati, Ohio, 45219, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Cetero Research DGD Research Inc.

San Antonio, Texas, 78229, United States

Location

The Vancouver Clinic

Vancouver, Washington, 98664, United States

Location

Related Publications (5)

• Ayodele O, Rejnmark L, Mu F, Lax A, Berman R, Swallow E, Gosmanova EO. Five-Year Estimated Glomerular Filtration Rate in Adults with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study. Adv Ther. 2022 Nov;39(11):5013-5024. doi: 10.1007/s12325-022-02292-1. Epub 2022 Aug 26.

  PMID: 36018496 DERIVED

• Rejnmark L, Ayodele O, Lax A, Mu F, Swallow E, Gosmanova EO. The risk of chronic kidney disease development in adult patients with chronic hypoparathyroidism treated with rhPTH(1-84): A retrospective cohort study. Clin Endocrinol (Oxf). 2023 Apr;98(4):496-504. doi: 10.1111/cen.14813. Epub 2022 Aug 28.

  PMID: 35974422 DERIVED

• 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.

  PMID: 35696069 DERIVED

• 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.

  PMID: 32738041 DERIVED

• 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.

  PMID: 31369089 DERIVED

MeSH Terms

Conditions

Hypoparathyroidism

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2011
• First Posted: February 16, 2011
• Study Start: April 6, 2011
• Primary Completion: June 8, 2018
• Study Completion: June 8, 2018
• Last Updated: May 25, 2021
• Results First Posted: August 6, 2019

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (14)