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HypoparathyroidismPhase 3NCT01297309

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)

A Phase 3 study testing NPSP558 in people with Hypoparathyroidism, run by Shire at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Hypoparathyroidism
What is being tested?
NPSP558
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
14 sitesUnited States
Study dates
6 Apr 2011to 8 Jun 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • University of Cincinnati Bone Health and Osteoporosis Center

    Cincinnati, Ohio, 45219

  • Michigan Bone & Mineral Clinic PC

    Detroit, Michigan, 48236

  • Physician East PA

    Greenville, North Carolina, 27834

  • Indiana University School of Medicine

    Indianapolis, Indiana, 46202

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • Advance Medical Research LLC

    Lakewood, California, 90712

  • Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • Cetero Research DGD Research Inc.

    San Antonio, Texas, 78229

  • University Physicians Group

    Staten Island, New York, 10301

  • The Vancouver Clinic

    Vancouver, Washington, 98664

Other trials in United States

About this study

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)

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

Read the 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.

Being tested
NPSP558
Keywords
PTH 1-84, Hypoparathyroidism, Parathyroid Hormone 1-84, NPSP558
Medical subject headings
Hypoparathyroidism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NPSP558Drug

    Also called RACE

    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.

Study groups in NCT01297309
Study groupRoleWhat they receive
NPSP558Experimentaltitration of 25, 50, 75 or 100 μg
Receives: Drug: NPSP558

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From start of study drug administration up to follow-up (82 months)

  2. 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.

    Measured: Week 52

  3. 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.

    Measured: EOT (up to 82 months)

Secondary outcomes (11)

  1. 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.

    Measured: Baseline, Week 52 and EOT (up to 82 months)

  2. 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.

    Measured: Baseline, Week 52 and EOT (up to 82 months)

  3. 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.

    Measured: Baseline, EOT (up to 82 months)

  4. 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.

    Measured: Baseline, EOT (up to 82 months)

  5. 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.

    Measured: Baseline, EOT (up to 82 months)

  6. 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.

    Measured: Baseline, EOT (upto 82 months)

  7. 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.

    Measured: Baseline, Month 72, EOT (upto 82 months)

  8. 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).

    Measured: EOT (up to 82 months)

  9. 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.

    Measured: Baseline, EOT (up to 82 months)

  10. 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.

    Measured: Baseline, EOT (up to 82 months)

  11. 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.

    Measured: Baseline, Week 52 and EOT (up to 82 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2011 (estimated)
  2. Study start6 Apr 2011
  3. Primary completion8 Jun 2018
  4. Study completion8 Jun 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01297309
Sponsor's protocol ID
PAR-C10-008
Status last verified
May 2021
First submitted
11 Feb 2011
Last updated
25 May 2021
Data monitoring committee
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 36018496

  • 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.

    PubMed 35974422

  • 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.

    PubMed 35696069

  • 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.

    PubMed 32738041

  • 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.

    PubMed 31369089

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing NPSP558 in people with Hypoparathyroidism, run by Shire at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01297309, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2021.

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