Clinical trial NCT01297309: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypoparathyroidism
Keywords: PTH 1-84
Hypoparathyroidism
Parathyroid Hormone 1-84
NPSP558
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-02-16
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE)
timeFrame: From start of study drug administration up to follow-up (82 months)
measure: Number of Responders With Calcium Source at Week 52
timeFrame: Week 52
measure: Number of Responders With Calcium Source at End Of Treatment (EOT) (Up to 82 Months)
timeFrame: EOT (up to 82 months)
Secondary outcomes:
measure: Percent Change From Baseline in Oral Calcium Supplementation at Week 52 and EOT (Up to 82 Months)
timeFrame: Baseline, Week 52 and EOT (up to 82 months)
measure: Percent Change From Baseline in Oral Calcitriol Supplementation at Week 52 and EOT (Up to 82 Months)
timeFrame: Baseline, Week 52 and EOT (up to 82 months)
measure: Percent Change From Baseline in Albumin Corrected Total Serum Calcium (ACSC) at EOT (Up to 82 Months)
timeFrame: Baseline, EOT (up to 82 months)
measure: Change From Baseline in 24-Hour Urine Calcium Excretion Through EOT (Up to 82 Months)
timeFrame: Baseline, EOT (up to 82 months)
measure: Change From Baseline in 24-hour Urine Calcium Excretion in Participants Who Used Calcium-Sparing Diuretics Through EOT (Up to 82 Months)
timeFrame: Baseline, EOT (up to 82 months)
measure: Change From Baseline in Serum Calcium Concentration in Participants Who Used and Calcium Sparing Diuretics at EOT (Upto 82 Months)
timeFrame: Baseline, EOT (upto 82 months)
measure: Change From Baseline in Serum Phosphate at Month 72 and EOT (Upto 82 Months)
timeFrame: Baseline, Month 72, EOT (upto 82 months)
measure: Number of Participants Who Maintained a Calcium Phosphate Product in A Normal Range at EOT (Up to 82 Months)
timeFrame: EOT (up to 82 months)
measure: Change From Baseline in Bone Turnover Markers at EOT (Up to 82 Months)
timeFrame: Baseline, EOT (up to 82 months)
measure: Change From Baseline in Serum Carboxy Terminal Telopeptide of Type I Collagen (s-CTx) Bone Turnover Marker at EOT (Up to 82 Months)
timeFrame: Baseline, EOT (up to 82 months)
measure: Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months)
timeFrame: Baseline, Week 52 and EOT (up to 82 months)
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: Advance Medical Research LLC
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Michigan Bone & Mineral Clinic PC
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Staten Island
country: United States
facility: University Physicians Group
state: New York
city: Greenville
country: United States
facility: Physician East PA
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Bone Health and Osteoporosis Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: San Antonio
country: United States
facility: Cetero Research DGD Research Inc.
state: Texas
city: Vancouver
country: United States
facility: The Vancouver Clinic
state: Washington
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.