A Study to Investigate the Safety and Efficacy of rhPTH(1-84) in Subjects with Hypoparathyroidism.

• Register: EUCTR
• Last refreshed on: 20 July 2020
• Main ID: EUCTR2017-003067-36-DK
• Date of registration: 08/06/2018
• Prospective Registration: Yes
• Primary sponsor: Shire Human Genetic Therapies, Inc.
• Public title: A Study to Investigate the Safety and Efficacy 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: 08/08/2018
• Target sample size: 32
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003067-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Denmark, Hungary, United States

Contacts

• Name: Robert Homolka
• Affiliation: Shire Human Genetic Therapies, Inc.

• Name: Robert Homolka
• Affiliation: Shire Human Genetic Therapies, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. An understanding, ability, and willingness to fully comply with study procedures and restrictions.
2. Ability to voluntarily provide written, signed, and dated informed consent to participate in the study.
3. Previously completed the SHP634-101 study, including the 30-day follow-up.
4. 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 31
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1. Received investigational study drug, aside from that received in study SHP634-101, within 3 months prior to the screening visit.
2. 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.
3. 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.
4. Subjects with a history of parathyroid hormone intolerance, based on investigator determination.
5. 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.
6. 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.
7. Use of the following medications prior to administration of investigational product within:
•30 days–loop diuretics, lithium, systemic corticosteroids (medical judgment is required by the investigator. Primarily high doses of systemic corticosteroids [eg, prednisone] should be excluded. Stable doses of hydrocortisone [eg, as treatment for Addison’s disease] may be acceptable).
•3 months–cinacalcet hydrochloride
•6 months–fluoride tablets, oral bisphosphonates, methotrexate, growth hormone, digoxin
•12 months–intravenous bisphosphonates, drug or alcohol abuse, as determined by the investigator
8. Presence of any clinically significant results from laboratory tests, vital signs assessments, or ECGs, that in the opinion of the investigator, would make the subject unsuitable for this study.
9. Any medical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for this study.
10. 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.
11. 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.
12. History of an allergic response(s) to PTH, PTH, or PTH(1-34) analogs, or other clinically significant allergies, that in the opinion of the investigator, would make the subject unsuitable for this study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Body processes [G] - Biological Phenomena [G16]

Hypoparathyroidism
MedDRA version: 20.0 Level: PT Classification code 10051315 Term: Congenital hypoparathyroidism System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0 Level: PT Classification code 10075900 Term: Primary hypoparathyroidism System Organ Class: 10014698 - Endocrine disorders
MedDRA version: 20.0 Level: PT Classification code 10021041 Term: Hypoparathyroidism System Organ Class: 10014698 - Endocrine disorders

Intervention(s)

Trade Name: Natpara
Product Name: Human recombinant parathyroid Hormone
Product Code: rhPTH(1-84)
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: PARATHYROID HORMONE
CAS Number: 9002-64-6
Current Sponsor code: SHP634
Other descriptive name: Parathyroid Hormone
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Natpara
Product Name: Human recombinant parathyroid Hormone
Product Code: rhPTH(1-84)
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: PARATHYROID HORMONE
CAS Number: 9002-64-6
Current Sponsor code: SHP634
Other descriptive name: Parathyroid Hormone
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Natpara
Product Name: Human recombinant parathyroid Hormone
Product Code: rhPTH(1-84)
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: PARATHYROID HORMONE
CAS Number: 9002-64-6
Current Sponsor code: SHP634
Other descriptive name: Parathyroid Hormone
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 75-

Trade Name: Natpara
Product Name: Human recombinant parathyroid Hormone
Product Code: rhPTH(1-84)
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: PARATHYROID HORMONE
CAS Number: 9002-64-6
Current Sponsor code: SHP634
Other descriptive name: Parathyroid Hormone
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Efficacy Endpoint:
at Visit 6 (Week 24) and at EOT/ET (Visit 9;Week 52).

Safety Endpoint:
at each assessment visit.

Primary end point(s): The primary efficacy endpoint is:
Subject response satisfying total serum calcium (albumin-corrected) values in the range of 7.5 mg/dL (1.875 mmol/L)-ULN at Visit 6 (Week 24) and at EOT/ET (Visit 9;Week 52).

The following safety variables constitute the safety endpoints measured in this study:
-Adverse events including SAEs
-Laboratory safety data (eg, clinical chemistry, hematology, and urinalysis)
-Vital signs including body temperature, heart rate (beats per minute), and blood pressure (systolic and diastolic [mmHg])
-ECG parameters
-Measurements of estimated glomerular filtration rate (eGFR) and creatinine
-Change from baseline in anti-PTH antibodies

Main Objective: To evaluate the proportion of subjects who achieve total serum calcium (albumin-corrected) values in the range of 7.5 mg/dL (1.875 mmol/L) – upper limit of normal (ULN) and to further characterize the safety of rhPTH(1-84) in adult subjects with hypoparathyroidism.

Secondary Objective: To evaluate biochemical responses to rhPTH(1-84) through 1 year of treatment.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints are:
-Change from baseline in ACSC concentration
-Change from baseline in serum phosphate concentration
-Change from baseline in ACSC-phosphate product
-Change from baseline in 24-hour urine calcium excretion
-Percentage changes from baseline in prescribed supplemental oral calcium dose
-Percentage changes from baseline in prescribed supplemental active vitamin D dose
-Percentage changes from baseline in markers of bone turnover

Timepoint(s) of evaluation of this end point: Efficacy Endpoint:
at each assessment visit.

Secondary ID(s)

SHP634-404

2017-003067-36-HU

NCT03364738

Source(s) of Monetary Support

Shire Human Genetic Therapies, Inc.

Ethics review

Status: Approved
Approval date: 28/06/2018
Contact: