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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)

Primary Purpose

Hypoparathyroidism

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

NPSP558

About this trial

This is an interventional treatment trial for Hypoparathyroidism focused on measuring PTH 1-84, Hypoparathyroidism, Parathyroid Hormone 1-84, NPSP558

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NPSP558

Arm Description

titration of 25, 50, 75 or 100 μg

Outcomes

Primary Outcome Measures

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.

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.

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

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

Full Information

NCT ID

NCT01297309

First Posted

February 11, 2011

Last Updated

May 19, 2021

Sponsor

Shire

1. Study Identification

Unique Protocol Identification Number

NCT01297309

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)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

April 6, 2011 (Actual)

Primary Completion Date

June 8, 2018 (Actual)

Study Completion Date

June 8, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shire

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypoparathyroidism

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

51 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NPSP558

Arm Type

Experimental

Arm Description

titration of 25, 50, 75 or 100 μg

Intervention Type

Drug

Intervention Name(s)

NPSP558

Other Intervention Name(s)

RACE

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE)

Description

Time Frame

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

Title

Number of Responders With Calcium Source at Week 52

Description

Time Frame

Week 52

Title

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

Description

Time Frame

EOT (up to 82 months)

Secondary Outcome Measure Information:

Title

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

Description

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.

Time Frame

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

Title

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

Description

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.

Time Frame

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

Title

Percent Change From Baseline in Albumin Corrected Total Serum Calcium (ACSC) at EOT (Up to 82 Months)

Description

Percent change in ACSC was reported. EOT was defined as the last determination of response or last available measurement during the treatment period.

Time Frame

Baseline, EOT (up to 82 months)

Title

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

Description

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.

Time Frame

Baseline, EOT (up to 82 months)

Title

Change From Baseline in 24-hour Urine Calcium Excretion in Participants Who Used Calcium-Sparing Diuretics Through EOT (Up to 82 Months)

Description

Time Frame

Baseline, EOT (up to 82 months)

Title

Change From Baseline in Serum Calcium Concentration in Participants Who Used and Calcium Sparing Diuretics at EOT (Upto 82 Months)

Description

Time Frame

Baseline, EOT (upto 82 months)

Title

Change From Baseline in Serum Phosphate at Month 72 and EOT (Upto 82 Months)

Description

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.

Time Frame

Baseline, Month 72, EOT (upto 82 months)

Title

Number of Participants Who Maintained a Calcium Phosphate Product in A Normal Range at EOT (Up to 82 Months)

Description

The normal range of calcium phosphate product is defined as <= 4.441 millimoles square per liter square (mmol^2/L^2).

Time Frame

EOT (up to 82 months)

Title

Change From Baseline in Bone Turnover Markers at EOT (Up to 82 Months)

Description

Time Frame

Baseline, EOT (up to 82 months)

Title

Change From Baseline in Serum Carboxy Terminal Telopeptide of Type I Collagen (s-CTx) Bone Turnover Marker at EOT (Up to 82 Months)

Description

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.

Time Frame

Baseline, EOT (up to 82 months)

Title

Change From Baseline in Bone Mineral Density (BMD) at Week 52 and EOT (Up to 82 Months)

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Study Director

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

Advance Medical Research LLC

City

Lakewood

State/Province

California

ZIP/Postal Code

90712

Country

United States

Facility Name

Mayo Clinic Jacksonville

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32224

Country

United States

Facility Name

University of Chicago Medical Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Indiana University School of Medicine

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Michigan Bone & Mineral Clinic PC

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48236

Country

United States

Facility Name

Mayo Clinic Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

Columbia University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

University Physicians Group

City

Staten Island

State/Province

New York

ZIP/Postal Code

10301

Country

United States

Facility Name

Physician East PA

City

Greenville

State/Province

North Carolina

ZIP/Postal Code

27834

Country

United States

Facility Name

University of Cincinnati Bone Health and Osteoporosis Center

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45219

Country

United States

Facility Name

Children's Hospital of Philadelphia

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Cetero Research DGD Research Inc.

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

The Vancouver Clinic

City

Vancouver

State/Province

Washington

ZIP/Postal Code

98664

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing 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.

IPD Sharing URL

https://vivli.org/ourmember/takeda/

Citations:

PubMed Identifier

35696069

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.

Results Reference

derived

PubMed Identifier

32738041

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.

Results Reference

derived

PubMed Identifier

31369089

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.

Results Reference

derived

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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)

Hypoparathyroidism

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial