A Study of Extended Use of Recombinant Human Parathyroid Hormone (rhPTH(1-84)) in Hypoparathyroidism

NCT02910466 | Completed Phase 4 Results FDA Drug

• 1 other identifier: SHP634-402
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic hypoparathyroidism is a life-long and irreversible disease for which the chronic administration of rhPTH(1-84) is a potential treatment option. The group of participants in the AAAE0544 core study has been taking rhPTH(1-84) for the treatment of hypoparathyroidism for up to 11 years. This study is designed to extend this experience and gain knowledge about how safe and effective rhPTH(1-84) is in participants with hypoparathyroidism over a long-term duration.

Conditions

Chronic Hypoparathyroidism; Hypoparathyroidism

Outcome Measures

Primary Outcomes (7)

• Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 6

  Baseline (402) was defined as the last available pre-dose value in SHP634-402.

  Baseline (402), Month 6

• Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 12

  Baseline (402) was defined as the last available pre-dose value in SHP634-402.

  Baseline (402), Month 12

• Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 18

  Baseline (402) was defined as the last available pre-dose value in SHP634-402.

  Baseline (402), Month 18

• Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 24

  Baseline (402) was defined as the last available pre-dose value in SHP634-402.

  Baseline (402), Month 24

• Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 30

  Baseline (402) was defined as the last available pre-dose value in SHP634-402.

  Baseline (402), Month 30

• Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 36

  Baseline (402) was defined as the last available pre-dose value in SHP634-402.

  Baseline (402), Month 36

• Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at End of Treatment (EOT) (up to Month 36)

  Baseline (402) was defined as the last available pre-dose value in SHP634-402. EOT was defined as the last determination of response during the treatment period (from the date of first dose to the date of last dose + 1 day), was analyzed in addition to the scheduled visits.

  Baseline (402), EOT (up to Month 36)

Secondary Outcomes (19)

• Percentage of Participants Who Achieved ACSC Concentrations Above, Below, or in the Range of 1.875 mmol/L (7.5 Milligram Per Deciliter [mg/dL]) to Upper Limit of Normal (ULN) at Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)

  At Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)

• Change From Baseline (402) in Urinary Calcium Excretion at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

  Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

• Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

  Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

• Change From Baseline (402) in Calcium Supplement Doses and Elemental Calcium Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

  Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

• Change From Baseline (402) in Active Vitamin D Supplement Dose Based on Investigator-prescribed Data and Diary Data at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

  Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)

Study Arms (1)

rhPTH(1-84)

EXPERIMENTAL

Participants will receive 25, 50, 75, and 100 microgram (mcg) of rhPTH(1-84) subcutaneous injection to the thigh via a multidose pen injector device once daily for 36 months. The dose will be individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion to achieve a serum calcium level in the lower half of the normal range.

Drug: rhPTH(1-84)

Interventions

rhPTH(1-84) DRUG

Participants will receive 25, 50, 75, and 100 microgram (mcg) of rhPTH(1-84) subcutaneous injection to the thigh via a multidose pen injector device once daily for 36 months. The dose will be individualized based on Albumin-corrected Serum Calcium (ACSC) and 24-hour calcium urinary excretion to achieve a serum calcium level in the lower half of the normal range.

rhPTH(1-84)

Eligibility Criteria

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

You may qualify if:

• Participants that are currently or previously enrolled in the core study (AAAE0544 \[NCT01199614\]) and have maintained uninterrupted therapy with recombinant human parathyroid hormone (rhPTH(1-84)) (transient interruptions of up to 1 month continuously off treatment may be allowed).
• Signed and dated informed consent form (ICF).
• Adult men and women 18 to 85 years of age.
• History of hypoparathyroidism for at least 12 months prior to rhPTH(1-84) treatment, defined by the requirement for supplemental calcium and/or active vitamin D to maintain serum calcium along with an undetectable or insufficient Parathyroid hormone (PTH) concentration.
• Able to perform daily subcutaneous (SC) self-injections of study medication (or have designee perform injection).
• Willingness and ability to understand and comply with the protocol. Women must agree to pregnancy testing and acceptable methods of contraception, as detailed in the protocol.

You may not qualify if:

• The participant is treated or has been treated with any investigational drug, aside from rhPTH(1-84), within 30 days of consent.
• As assessed by the investigator, the participant has any safety or medical issues that contraindicate participation in the study.
• The participant and/or the participant's parent(s) or legally-authorized representative(s) are unable to understand the nature, scope, and possible consequences of the study.
• The participant is unable to comply with the protocol, example, uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for evaluations, or is otherwise unlikely to complete the study, as determined by the investigator or the medical monitor.
• The participant is pregnant or lactating.
• Participants who are at increased baseline risk for osteosarcoma such as participant with Paget's disease of bone or unexplained new elevations of alkaline phosphatase, participants with hereditary disorders predisposing to osteosarcoma or participants with a prior history of external beam or implant radiation therapy involving the skeleton.

Sponsors & Collaborators

• Shire: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (4)

• 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

• 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

• Tay YD, Tabacco G, Cusano NE, Williams J, Omeragic B, Majeed R, Gomez Almonte M, Bilezikian JP, Rubin MR. Therapy of Hypoparathyroidism With rhPTH(1-84): A Prospective, 8-Year Investigation of Efficacy and Safety. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5601-5610. doi: 10.1210/jc.2019-00893.

  PMID: 31310310 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

  Shire

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2016
• First Posted: September 22, 2016
• Study Start: October 27, 2016
• Primary Completion: December 20, 2019
• Study Completion: December 20, 2019
• Last Updated: July 28, 2021
• Results First Posted: July 28, 2021

Record last verified: 2021-07

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 (1)