Symptom Improvement Evaluation and Metabolic control among Adult Subjects with Symptomatic Hypoparathyroidism Treated with Recombinant Human Parathyroid hormone [rhPTH(1-84)]

• Register: EUCTR
• Last refreshed on: 4 April 2022
• Main ID: EUCTR2017-000284-32-SE
• Date of registration: 02/11/2017
• Prospective Registration: Yes
• Primary sponsor: Shire Human Genetic Therapies, Inc.
• Public title: Symptom Improvement Evaluation and Metabolic control among Adult Subjects with Symptomatic Hypoparathyroidism Treated with Recombinant Human Parathyroid hormone [rhPTH(1-84)]
• Scientific title: A Randomized, Double-blind, Placebo-controlled, Adaptive Study to Evaluate Symptom Improvement and Metabolic Control Among Adult Subjects With Symptomatic Hypoparathyroidism Treated With Recombinant Human Parathyroid Hormone [rhPTH(1-84)]
• Date of first enrolment: 18/01/2018
• Target sample size: 92
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000284-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Adaptive If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): yes

Countries of recruitment

Belgium, Canada, Denmark, France, Germany, Italy, Netherlands, Norway, Portugal, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Elena Tokareva
• Affiliation: Shire Human Genetic Therapies, Inc

• Name: Elena Tokareva
• Affiliation: Shire Human Genetic Therapies, Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Has an understanding, ability, and willingness to fully comply with study procedures and
restrictions.
2. Is able to voluntarily provide a signed and dated informed consent form before any study-related procedures are performed.
3. Is an adult male or female 18 to 85 years of age, inclusive.
4. In subjects 18-25 years of age or younger, has radiological evidence of epiphyseal closure based on X-ray of left wrist and left hand before randomization.
5. Has chronic hypoparathyroidism with onset 12 months or more before screening. The diagnosis of hypoparathyroidism is established based on hypocalcemia in the setting of inappropriately low serum PTH levels.
6. During the Week -3 screening visit, the subject reports by history at least 2 of the following symptoms related to hypoparathyroidism occurring within the 2 weeks before Week -3 visit: muscle cramps, muscle spasms or twitching, tingling, numbness, heaviness in arms or legs, physical fatigue, or slowed or confused thinking (brain fog).
7. The subject must have a Hypoparathyroidism Symptom Diary (HPT-SD) symptom subscale Sum Score of =10 during the 14-day period immediately prior to the baseline (Week 0) visit (Day -14 to Day -1). In addition, the subject must have at least 4 HPT-SD diaries completed in the first 7 day period and at least 4 HPT-SD diaries completed in second 7 day period. See Appendix 3 for the calculation of the sum score
8. Must be treated with active vitamin D (calcitriol or alfacalcidol) alone or in conjunction with calcium supplements for at least 4 months prior to the screening visit.
. The subject must be taking =0.5 µg/day of calcitriol or =1.0 µg/day of alfacalcidol.
. If the subject is treated with a lower dose of active vitamin D the subject must also be taking calcium supplements of at least 800 mg/day of elemental calcium
9. Has thyroid-stimulating hormone (TSH) results within normal laboratory limits at screening for all subjects not receiving thyroid hormone replacement therapy. For subjects on thyroid hormone replacement therapy, the thyroid hormone dose must have been stable for at least 4 weeks before screening, and serum TSH level must be within the
central laboratory normal range. A serum TSH level below the lower limit of the normal range but not undetectable in subjects treated with thyroid hormone may be allowed if there is no anticipated need for a change in thyroid hormone dose during the trial.
10. Has serum 25-hydroxyvitamin D levels =50 nmol/L (20 ng/mL) and <1.5 times the upper limit of normal (ULN) for the central laboratory normal range.
11. Has estimated glomerular filtration rate (eGFR) >30 ml/min/1.73m2.
12. Prior to randomization, is able to perform daily SC self-injections of study medication (or have a designee perform injection) via a multidose injection pen into the thigh.
13. Willing to use oral active vitamin D and calcium supplements provided for the study unless directed to remain on the supplements used prior to enrollment in the current study by the investigator after consultation with the medical monitor
14. With regard to female subjects: women who are postmenopausal (12 consecutive months
of spontaneous amenorrhea and age more than or equal to 51 years) and women who are surgically sterilized can be enrolled. Women of childbearing potential must have a negative pregnancy test at
randomization and be willing to comply with any applicable contraceptive requirements of the protocol and pregnancy testing for the duration
Exclusion criteria:
1. History of hypoparathyroidism resulting from a known activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism).
2. Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, such as poorly controlled hyperthyroidism; Paget disease; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus; severe and chronic cardiac, liver (Child-Pugh score >9) (US FDA, 2003), or renal disease; Cushing syndrome; rheumatoid arthritis; myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy (other than low-risk well differentiated thyroid cancer); primary or secondary hyperparathyroidism; or documented parathyroid carcinoma within the previous 5 years, acromegaly, or multiple endocrine neoplasia types
1 and 2.
3. Very low or very high blood calcium level (eg, ACSC <1.87 mmol/L [<7.5 mg/dL] or
=2.97 mmol/L [=11.9 mg/dL]) at the Week -3 screening visit. Results from the central laboratory must be used for this assessment
4. If the Blood calcium level is above the ULN at the baseline (Week 0) visit, the analysis can be repeated another day as long as the next date is within the visit window for the baseline visit. If the subject does not met exclusion #4 on the repeat measure the subject may be randomized.
5. Use of prohibited medications, such as loop and thiazide diuretics, phosphate binders (other than calcium carbonate), digoxin, lithium, methotrexate, or systemic corticosteroids, within respective prohibited periods. See Section 5 (Prior and Concomitant Treatment) for a list of prohibited and restricted medications
6. Participation in any other investigational study in which receipt of investigational drug or device occurred within 6 months before screening for this study. Prior treatment with PTH-like drugs (whether commercially available or through participation in an
investigational study), including PTH(1-84), PTH(1-34), or other N-terminal fragments or analogs of PTH or PTH-related protein, within 3 months before screening.
7. Use of other drugs known to influence calcium and bone metabolism, such as calcitonin, fluoride tablets, or cinacalcet hydrochloride, within the prohibited period.
8. Use of oral bisphosphonates within the previous 6 months or intravenous bisphosphonate
preparations within the previous 24 months before screening.
9. Nonhypocalcemic seizure disorder with a history of a seizure within the previous 6 months before screening. Subjects with a history of seizures that occur in the setting of hypocalcemia are allowed.
10. The subject is at increased baseline risk for osteosarcoma, such as those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, hereditary disorders predisposing to osteosarcoma, or with a prior history of external beam or implant radiation therapy involving the skeleton.
11. Any disease or condition that, in the opinion of the investigator, may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures. For example, illness that is anticipated to be chronic and not transient.
12. Pregnant or lactating women.
13. Known or suspected intolerance or hypersensitivity to the investigational product, closely-related compounds, or any of the stated ingredients. Refer to the investigator’s brochure for the list o

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

Health Condition(s) or Problem(s) studied

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

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

Intervention(s)

Trade Name: Natpar
Product Name: human recombinant parathyroid hormone
Product Code: rhPTH(1-84)
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: RECOMBINANT HUMAN PARATHYROID HORMONE (1-84)
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-
Pharmaceutical form of the placebo: Lyophilisate and solvent for solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Natpar
Product Name: human recombinant parathyroid hormone
Product Code: rhPTH(1-84)
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: RECOMBINANT HUMAN PARATHYROID HORMONE (1-84)
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-
Pharmaceutical form of the placebo: Lyophilisate and solvent for solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Natpar
Product Name: human recombinant parathyroid hormone
Product Code: rhPTH(1-84)
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: RECOMBINANT HUMAN PARATHYROID HORMONE (1-84)
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-
Pharmaceutical form of the placebo: Lyophilisate and solvent for solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Natpar
Product Name: human recombinant parathyroid hormone
Product Code: rhPTH(1-84)
Pharmac

Primary Outcome(s)

Main Objective: To test the hypothesis that rhPTH(1-84) treatment can result in superior improvements in the symptoms of hypoparathyroidism assessed by the hypoparathyroidism Symptom Diary (HPT-SD) symptom subscale compared with standard therapy.

Secondary Objective: The key secondary objectives are to test the hypotheses that rhPTH(1-84) treatment can result in
superior improvements in:

Fatigue assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) compared with standard therapy.

The physical component summary (PCS) derived from the 36-Item Short Form Health Survey version 2
(SF-36v2) acute version compared with standard therapy.

Timepoint(s) of evaluation of this end point: Week 26 from baseline

Primary end point(s): Change in the HPT-SD symptom subscale score from baseline to Week 26

Secondary Outcome(s)

Secondary end point(s): Change in FACIT-Fatigue score at Week 26
Change in the PCS derived from SF-36v2 scores at Week 26

Timepoint(s) of evaluation of this end point: Week 26 from baseline

Secondary ID(s)

SHP634-401

2017-000284-32-GB

Source(s) of Monetary Support

Shire Human Genetic Therapies, Inc.

Ethics review

Status: Approved
Approval date: 18/01/2018
Contact: