Clinical trial NCT02910466: A Study of Extended Use of Recombinant Human Parathyroid Hormone (rhPTH(1-84)) in Hypoparathyroidism
Official title: A Phase 4, Open-Label, Single-Center Clinical Study of Extended Use of rhPTH(1-84) in Hypoparathyroidism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hypoparathyroidism
Hypoparathyroidism
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-09-22
Enrollment: 39
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: 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.


Eligibility criteria: Inclusion Criteria

* 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.

Exclusion Criteria

* 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.

Primary outcomes:
measure: Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 6
timeFrame: Baseline (402), Month 6
measure: Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 12
timeFrame: Baseline (402), Month 12
measure: Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 18
timeFrame: Baseline (402), Month 18
measure: Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 24
timeFrame: Baseline (402), Month 24
measure: Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 30
timeFrame: Baseline (402), Month 30
measure: Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at Month 36
timeFrame: Baseline (402), Month 36
measure: Change From Baseline (402) in Concentration of Albumin-corrected Serum Calcium (ACSC) at End of Treatment (EOT) (up to Month 36)
timeFrame: Baseline (402), EOT (up to Month 36)
Secondary outcomes:
measure: 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)
timeFrame: At Month 6, 12, 18, 24, 30, 36 and EOT (up to Month 36)
measure: Change From Baseline (402) in Urinary Calcium Excretion at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Concentration of Serum Phosphate Levels at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: 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)
timeFrame: Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: 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)
timeFrame: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Hypoparathyroidism Symptoms Diary (HPT-SD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Total Score at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Hospital Anxiety and Depression Scale (HADS) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey at Month 12, 24, 36, and EOT (up to Month 36)
timeFrame: Baseline (402), At Month 12, 24, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Concentration of Bone Turnover Markers at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Concentration of Bone Turnover Marker for Bone Specific Alkaline Phosphatase and Tartrate-resistant Acid Phosphatase-5b at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Bone Mineral Density (BMD) at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) for Total T-scores at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline, At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Change From Baseline (402) in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) for Total Area of Radius and Tibia at Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
timeFrame: Baseline (402), At Month 6, 12, 18, 24, 30, 36, and EOT (up to Month 36)
measure: Mean Bone Histology (Biopsy) of Adjusted Apposition Rate and Cancellous Minimum Apposition Rate at Month 12, and EOT (up to Month 36)
timeFrame: At Month 12, and EOT (up to Month 36)
measure: Mean Bone Histology (Biopsy) of Bone Formation Rate at Month 12, and EOT (up to Month 36)
timeFrame: At Month 12, and EOT (up to Month 36)
measure: Mean Bone Histology (Biopsy) of Cancellous Bone Volume, Cancellous Eroded Surface, Cancellous Mineral Surface, And Cancellous Osteoid Surface at Month 12, and EOT (up to Month 36)
timeFrame: At Month 12, and EOT (up to Month 36)
measure: Mean Bone Histology (Biopsy) of Cancellous Osteoid Thickness and Cortical Width at Month 12, and EOT (up to Month 36)
timeFrame: At Month 12, and EOT (up to Month 36)
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References:
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: 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.