Safety and Efficacy Study of rhPTH(1-84) in Subjects With Hypoparathyroidism

• Register: ClinicalTrials.gov
• Last refreshed on: 10 October 2022
• Main ID: NCT03364738
• Date of registration: 20/11/2017
• Prospective Registration: Yes
• Primary sponsor: Shire
• Public title: Safety and Efficacy Study of rhPTH(1-84) in Subjects With Hypoparathyroidism
• Scientific title: An Open-label Study Investigating the Safety and Efficacy of rhPTH(1-84) in Subjects With Hypoparathyroidism
• Date of first enrolment: September 26, 2018
• Target sample size: 22
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03364738
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Canada, Denmark, Hungary, United States

Contacts

• Name: Study Director
• Affiliation: Shire

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Hypoparathyroidism

Intervention(s)

Biological: rhPTH(1-84)

Primary Outcome(s)

Number of Participants With Clinically Significant Change in Vital Sign [Time Frame: From start of study drug administration to end of study (Week 56)]

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [Time Frame: From start of study drug administration to end of study (Week 56)]

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]) [Time Frame: At Week 52 (EOT)]

Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters [Time Frame: From start of study drug administration to end of study (Week 56)]

Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 52 (EOT) [Time Frame: Week 52 (EOT)]

Number of Participants With Clinically Significant Change in Serum Creatinine Value [Time Frame: From start of study drug administration to end of study (Week 56)]

Number of Participants With Clinically Significant Change in Estimated Glomerular Filtration Rate (eGFR) Values [Time Frame: From start of study drug administration to end of study (Week 56)]

Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 24 [Time Frame: Week 24]

Number of Participants With Clinically Significant Change in Clinical Laboratory Values [Time Frame: From start of study drug administration to end of study (Week 56)]

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 [Time Frame: At Week 24]

Secondary Outcome(s)

Change From Baseline in Albumin Corrected Serum Calcium (ACSC) Concentration at Weeks 24 and 52 (EOT) [Time Frame: Baseline, Weeks 24 and 52 (EOT)]

Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) [Time Frame: Baseline, Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)]

Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) [Time Frame: Baseline, Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS)]

Percentage Change From Baseline in Procollagen 1 N-Terminal Propeptide at Weeks 8, 24 and 52 (EOT) [Time Frame: Baseline, Weeks 8, 24 and 52 (EOT)]

Change From Baseline in 24-hour Urine Calcium Excretion at Weeks 16, 32 and 52 (EOT) [Time Frame: Baseline, Weeks 16, 32 and 52 (EOT)]

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]) [Time Frame: Baseline and at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS)]

Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase at Weeks 8, 24 and 52 (EOT) [Time Frame: Baseline, Weeks 8, 24 and 52 (EOT)]

Percentage Change From Baseline in Type I Collagen C-Telopeptides at Weeks 8, 24 and 52 (EOT) [Time Frame: Baseline, Weeks 8, 24 and 52 (EOT)]

Percentage Change From Baseline in Serum Osteocalcin at Weeks 8, 24 and 52 (EOT) [Time Frame: Baseline, Weeks 8, 24 and 52 (EOT)]

Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) [Time Frame: Baseline, Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)]

Percentage Change From Baseline in Type I Collagen N-Telopeptides at Weeks 8, 24 and 52 (EOT) [Time Frame: Baseline, Weeks 8, 24 and 52 (EOT)]

Secondary ID(s)

SHP634-404

2017-003067-36

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 16/06/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03364738