Clinical trial NCT03364738: Safety and Efficacy Study of rhPTH(1-84) in Subjects With Hypoparathyroidism
Official title: An Open-label Study Investigating the Safety and Efficacy of rhPTH(1-84) in Subjects With Hypoparathyroidism
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hypoparathyroidism
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-12-07
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is open to adults with hypoparathyroidism who complete the SHP634-101 study (PARALLAX Study). The purpose of this study is to see if rhPTH(1-84) is safe and effective in adults with hypoparathyroidism who previously participated in the SHP634-101 study. All participants enrolled in this study will receive rhPTH(1-84) once-daily for 52 weeks via an injection.

Patients who complete the SHP634-101 study will have the option to screen for this extension study.


Eligibility criteria: Inclusion Criteria:

* An understanding, ability, and willingness to fully comply with study procedures and restrictions
* Ability to voluntarily provide written, signed, and dated informed consent to participate in the study.
* Previously completed the SHP634-101 (NCT02781844) study, including the 30-day follow-up.
* Male or non-pregnant, non-lactating female subjects who agree to comply with applicable contraceptive requirements of the protocol or females of non-childbearing potential.

Exclusion Criteria:

* Received investigational study drug, aside from that received in study SHP634-101 (NCT02781844), within 3 months prior to the screening visit.
* Presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine (with exception of the condition under study), or neurologic system(s) or psychiatric disease, that in the opinion of the investigator, would make the subject unsuitable for this study.
* Received parathyroid hormone (PTH), PTH analog, or parathyroid hormone fragment 1-34 \[PTH(1-34)\] treatment within the last 30 days from the screening visit.
* Subjects with a history of parathyroid hormone intolerance, based on investigator determination.
* Any disease that might affect calcium metabolism or calcium-phosphate homeostasis as determined by the investigator other than hypoparathyroidism, including but not limited to, active hyperthyroidism; poorly controlled insulin-dependent diabetes mellitus or type 2 diabetes mellitus; severe and chronic cardiac, liver or renal disease; Cushing's syndrome; neuromuscular disease such as rheumatoid arthritis; myeloma; pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy, bone metastases or a history of skeletal malignancies; primary or secondary hyperparathyroidism; a history of parathyroid carcinoma; hypopituitarism, acromegaly; or multiple endocrine neoplasia types 1 and 2 .
* Subjects who are at increased baseline risk for osteosarcoma such as subjects with Paget's disease of bone or unexplained elevations of alkaline phosphatase, young adult subjects with open epiphyses, subjects with hereditary disorders predisposing to osteosarcoma or subjects with a prior history of external beam or implant radiation therapy involving the skeleton.
* Use of the following medications prior to administration of investigational product within:

  1. 30 days-loop diuretics, lithium, systemic corticosteroids (medical judgment is required by the investigator. Primarily high doses of systemic corticosteroids \[example (eg), prednisone\] should be excluded. Stable doses of hydrocortisone \[eg, as treatment for Addison's disease\] may be acceptable).
  2. 3 months-cinacalcet hydrochloride
  3. 6 months-fluoride tablets, oral bisphosphonates, methotrexate, growth hormone, digoxin
  4. 12 months-intravenous bisphosphonates, drug or alcohol abuse, as determined by the investigator
* Presence of any clinically significant results from laboratory tests, vital signs assessments, or electrocardiograms (ECG), that in the opinion of the investigator, would make the subject unsuitable for this study.
* Any medical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for this study.
* History of a clinically significant illness during the 4 weeks prior to dosing, that in the opinion of the investigator, would make the subject unsuitable for this study.
* History of any clinically significant surgery or procedure within 8 weeks of first dose, as determined by the investigator or expected to undergo a major surgical procedure during the trial.
* History of an allergic response(s) to PTH, PTH analogs, or PTH(1-34), or other clinically significant allergies, that in the opinion of the investigator, would make the subject unsuitable for this study.

Primary outcomes:
measure: Percentage of Participants Who Achieved Total Albumin-corrected Serum Calcium (ACSC) Values Greater Than or Equal to (>=) to the Range of 7.5 mg/dL (1.875 mmol/L) and Less Than or Equal to (<=) Upper Limit of Normal (ULN) at Week 24
timeFrame: At Week 24
measure: Percentage of Participants With Total ACSC Values >= to the Range of 7.5 mg/dL (1.875 mmol/L) and <=ULN at Week 52 (End-of-treatment [EOT])
timeFrame: At Week 52 (EOT)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: From start of study drug administration to end of study (Week 56)
measure: Number of Participants With Clinically Significant Change in Clinical Laboratory Values
timeFrame: From start of study drug administration to end of study (Week 56)
measure: Number of Participants With Clinically Significant Change in Vital Sign
timeFrame: From start of study drug administration to end of study (Week 56)
measure: Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters
timeFrame: From start of study drug administration to end of study (Week 56)
measure: Number of Participants With Clinically Significant Change in Estimated Glomerular Filtration Rate (eGFR) Values
timeFrame: From start of study drug administration to end of study (Week 56)
measure: Number of Participants With Clinically Significant Change in Serum Creatinine Value
timeFrame: From start of study drug administration to end of study (Week 56)
measure: Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 24
timeFrame: Week 24
measure: Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 52 (EOT)
timeFrame: Week 52 (EOT)
Secondary outcomes:
measure: Change From Baseline in Albumin Corrected Serum Calcium (ACSC) Concentration at Weeks 24 and 52 (EOT)
timeFrame: Baseline, Weeks 24 and 52 (EOT)
measure: Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)
timeFrame: Baseline, Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)
measure: Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)
timeFrame: Baseline, Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)
measure: Change From Baseline in 24-hour Urine Calcium Excretion at Weeks 16, 32 and 52 (EOT)
timeFrame: Baseline, Weeks 16, 32 and 52 (EOT)
measure: Percentage Change From Baseline in Prescribed Supplemental Oral Calcium Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (End of Study [EOS])
timeFrame: Baseline and at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS)
measure: Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS)
timeFrame: Baseline, Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS)
measure: Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase at Weeks 8, 24 and 52 (EOT)
timeFrame: Baseline, Weeks 8, 24 and 52 (EOT)
measure: Percentage Change From Baseline in Serum Osteocalcin at Weeks 8, 24 and 52 (EOT)
timeFrame: Baseline, Weeks 8, 24 and 52 (EOT)
measure: Percentage Change From Baseline in Procollagen 1 N-Terminal Propeptide at Weeks 8, 24 and 52 (EOT)
timeFrame: Baseline, Weeks 8, 24 and 52 (EOT)
measure: Percentage Change From Baseline in Type I Collagen C-Telopeptides at Weeks 8, 24 and 52 (EOT)
timeFrame: Baseline, Weeks 8, 24 and 52 (EOT)
measure: Percentage Change From Baseline in Type I Collagen N-Telopeptides at Weeks 8, 24 and 52 (EOT)
timeFrame: Baseline, Weeks 8, 24 and 52 (EOT)
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Metairie
country: United States
facility: Crescent City Clinical Research Center, LLC
state: Louisiana
city: Reno
country: United States
facility: Northern Nevada Endocrinology - Lisa Abbott MD
state: Nevada
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Jefferson Rheumatology Associates
state: Pennsylvania
city: Oakville
country: Canada
facility: Bone Research and Education Centre
state: Ontario
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Pécs
country: Hungary
facility: Pecsi Tudomanyegyetem, I. sz. Belgyogyaszati Klinika
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: