| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
| Inappropriately low or undetectable levels of parathyroid hormone (PTH) circulated through the body |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Biological Phenomena [G16] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10051315 |
| E.1.2 | Term | Congenital hypoparathyroidism |
| E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10075900 |
| E.1.2 | Term | Primary hypoparathyroidism |
| E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10021041 |
| E.1.2 | Term | Hypoparathyroidism |
| E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate biochemical responses to rhPTH(1-84) through 1 year of treatment. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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.
|
|
| E.4 | Principal 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. |
|
| E.5 End points |
| E.5.1 | 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 |
|
| E.5.1.1 | 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. |
|
| E.5.2 | 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 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy Endpoint:
at each assessment visit. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 6 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Denmark |
| Hungary |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The Study Completion Date is defined as the date the final subject, across all sites, completes their final protocol-defined assessment. Please note that this includes the follow-up visit or contact, whichever is later. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 14 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 28 |
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