A Clinical Study of rhPTH(1-84) Treatment in Japanese Participants With Chronic Hypoparathyroidism

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2022
• Main ID: NCT03878953
• Date of registration: 15/03/2019
• Prospective Registration: Yes
• Primary sponsor: Shire
• Public title: A Clinical Study of rhPTH(1-84) Treatment in Japanese Participants With Chronic Hypoparathyroidism
• Scientific title: A Phase 3, Open-label Clinical Study of rhPTH(1-84) Treatment in Japanese Subjects With Chronic Hypoparathyroidism
• Date of first enrolment: August 31, 2022
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03878953
• 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

Japan

Contacts

• Name: Study Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

- The participant has signed and dated the informed consent form.

- The participant is an adult male or female 20 to 85 years of age inclusive.

- The participant is living in Japan and is Japanese; in this case, Japanese is defined
as having been born in Japan, with Japanese parents, and Japanese maternal and
paternal grandparents.

- The participant has a diagnosis of chronic hypoparathyroidism with an onset of 18
months or more prior to screening. The diagnosis is based on historical biochemical
evidence of hypocalcemia in the setting of a concomitant inappropriately low serum
intact parathyroid hormone (PTH). If such evidence is not available the diagnosis of
chronic hypoparathyroidism must be confirmed by the Shire medical monitor based on
other compelling medical history.

- The participant has been treated with active vitamin D therapy with alfacalcidol
greater than or equal to (>=) 1 microgram (mcg) per day (or an equivalent dose of
calcitriol of >=0.5 mcg per day or falecalcitriol >=0.3 mcg per day) prior to
baseline.

- The participant has indicated a willingness and ability to perform daily subcutaneous
(SC) self-injections of study medication (or will have a designee, ie, a family member
or caregiver, to perform injections).

- Females of childbearing potential must agree to comply with the contraceptive
requirements of the protocol.

- The participants who are less than (<) 25 years old demonstrate radiological evidence
of epiphyseal closure at screening based on bone age X-ray (single posteroanterior
X-ray of the left wrist and hand).

- The participant meets 1 of the following criteria:

1. If not receiving thyroid hormone replacement therapy, the participant has a serum
thyroid stimulating hormone (TSH) level within normal laboratory limits at
screening.

2. If receiving thyroid hormone replacement therapy, the dose must have been stable
for at least 3 months prior to screening and serum TSH level within the reference
range for the laboratory.

- The participant has a 25-hydroxyvitamin D level >=50 nanomoles per litre (nmol/L) (20
nanogram per milliliter [ng/mL]) and < upper limit of normal (ULN) of the laboratory
reference range.

- The participant has a serum creatinine laboratory value of <132.6 micromoles per liter
(mcmoles/L) (1.5 milligram per deciliter [mg/dL]).

- The participant has a serum magnesium level within the laboratory reference range at
baseline.

- The participant is not adequately controlled with standard therapy within 6 months of
screening based upon the opinion of the investigator and approval by the sponsor's
medical monitor. For example:

1. Hypocalcemia (albumin-corrected serum calcium <8.0 mg/dL) or

2. Hypercalciuria (urine calcium [mg/dL]/creatinine [mg/dL] ratio >0.4 or 24 hour
urine calcium excretion >7.5 millimoles (mmol) [300 milligram {mg}]/24 hours in
men and >6.25 millimoles (mmol) [250 mg]/24 hours in women) or,

3. Symptoms of hypoparathyroidism.

Exclusion Criteria:

- The participant and/or legally authorized representative(s) is unable to understand
the nature, scope, and possible consequences of the study.

- The participant is unable to comply with the protocol, eg, uncooperative with protocol
schedule, refusal to agree to all of the study procedures, inability to return for
evaluations, or is otherwise unlikely to complete the study, as determined by the
investigator or the medical monitor.

- The participant has any disease that might affect calcium metabolism or
calcium-phosphate homeostasis other than hypoparathyroidism, such as active
hyperthyroidism, Paget's disease, type 1 diabetes mellitus or poorly controlled type 2
diabetes mellitus (hemoglobin A1c [HbA1c] >8%), severe and chronic cardiac, liver or
renal disease, Cushing's syndrome, neuromuscular disease, rheumatoid arthritis,
myeloma, pancreatitis, malnutrition, rickets, recent prolonged immobility, active
malignancy, primary or secondary hyperparathyroidism, a history of parathyroid
carcinoma, hypopituitarism, acromegaly, or multiple endocrine neoplasia types I and
II.

- The participant has a known history of hypoparathyroidism resulting from an activating
mutation in the CaSR gene or impaired responsiveness to PTH
(pseudohypoparathyroidism).

- The participant is taking prohibited medications (listed below) or other drugs known
to influence calcium and bone metabolism during their respective prohibited periods.

a) The following prohibited medications should not be taken within the specified
number of days prior to the first dose of rhPTH(1-84): i) 30 days: loop diuretics,
thiazide diuretics, phosphate binders (other than calcium carbonate), calcitonin,
cinacalcet hydrochloride.

ii) 90 days: lithium. iii) 127 days: denosumab. iv) 180 days: digoxin, raloxifene
hydrochloride, estrogens and progestins for hormone replacement therapy, methotrexate,
systemic corticosteroids, oral bisphosphonates*.

v) 365 days: sodium fluoride, intravenous bisphosphonates*. Note: *The length of the
washout period is dependent on the route of administration of bisphosphonate that is being
used by the participant.

- The participant has previous treatment or participation in an investigational trial
with PTH-like drugs, including PTH(1-84), PTH(1-34) or other N terminal fragments or
analogs of PTH or PTH-related protein within 6 months prior to screening.

- The participant has nonhypocalcemic seizure disorder/epilepsy with a history of a
seizure within the previous 6 months prior to screening; note that participant with a
history of seizures due to hypocalcemia are allowed.

- The participant has any disease or condition, in the opinion of the investigator,
which has a high probability of precluding the participant from completing the study
or that the participant cannot or will not appropriately comply with study
requirements.

- The participant has participated in any other investigational trial in which receipt
of investigational drug or device occurred within 6 months prior to screening for this
study.

- The participant is pregnant or breastfeeding.

- The participant has a history of diagnosed drug or alcohol dependence within the
previous 3 years.

- The participant has a history of gout.

- The participant has disease processes that may adversely


Age minimum: 20 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Chronic Hypoparathyroidism

Intervention(s)

Drug: rhPTH(1-84)

Primary Outcome(s)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Time Frame: From start of study treatment up to 30 weeks]

Number of Responders at Week 26 [Time Frame: Week 26]

Secondary Outcome(s)

Change From Baseline in Serum Phosphate Level [Time Frame: Baseline, Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 26 and 30]

Change From Baseline in Urine Calcium Level [Time Frame: Baseline, Week 26]

Secondary ID(s)

JapicCTI-194828

SHP634-301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors