A Study to Learn if Recombinant Human Parathyroid Hormone [rhPTH(1-84)] Can Improve Symptoms and Metabolic Control in Adults With Hypoparathyroidism (BALANCE)

• Register: ClinicalTrials.gov
• Last refreshed on: 6 June 2022
• Main ID: NCT03324880
• Date of registration: 10/10/2017
• Prospective Registration: Yes
• Primary sponsor: Shire
• Public title: A Study to Learn if Recombinant Human Parathyroid Hormone [rhPTH(1-84)] Can Improve Symptoms and Metabolic Control in Adults With Hypoparathyroidism (BALANCE)
• 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: January 24, 2018
• Target sample size: 93
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03324880
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 4

Countries of recruitment

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

Contacts

• Name: Study Director
• Affiliation: Shire

Key inclusion & exclusion criteria

Inclusion Criteria:

- Has an understanding, ability, and willingness to fully comply with study procedures
and restrictions.

- Is able to voluntarily provide a signed and dated informed consent form before any
study-related procedures are performed.

- Is an adult male or female 18 to 85 years of age, inclusive.

- In participants 18-25 years of age, has radiological evidence of epiphyseal closure
based on bone age X-ray (single posteroanterior X-ray of left wrist and hand) before
randomization.

- 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.

- During the Week -3 screening visit, the participant 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).

- The participant must have a Hypoparathyroidism Symptom Diary (HPT-SD) symptom subscale
Sum Score of greater than or equal to (>=) 10 during the 14-day period immediately
prior to the baseline (Week 0) visit (Day -14 to Day -1). In addition, the participant
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.

- 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.

1. The participant must be taking >= 0.5 microgram (mcg)/day of calcitriol or >=1.0
mcg/day of alfacalcidol.

2. If the participant is treated with a lower dose of active vitamin D the
participant must also be taking calcium supplements of at least 800 milligrams
per day (mg/day) of elemental calcium.

- Has serum thyroid-stimulating hormone (TSH) results within normal laboratory limits at
screening for all participants not receiving thyroid hormone replacement therapy. For
participants 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 participant treated with thyroid hormone may
be allowed if there is no anticipated need for a change in thyroid hormone dose during
the trial.

- Has serum 25-hydroxyvitamin D levels >=50 nmol/L (nanomoles per liter) (20 nanograms
per milliliter [ng/mL]) and less than (<) 1.5 times the upper limit of normal (ULN)
for the central laboratory normal range.

- Has estimated glomerular filtration rate (eGFR) greater than (>) 30 milliliter per
minute per 1.73 square meters (ml/min/1.73m^2).

- 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.

- 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.

- With regard to female participants: women who are postmenopausal (12 consecutive
months of spontaneous amenorrhea and age >= 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 of
the study.

Exclusion Criteria:

- History of hypoparathyroidism resulting from a known activating mutation in the CaSR
gene or impaired responsiveness to PTH (pseudohypoparathyroidism).

- 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.

- 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.

- Blood calcium level above the ULN at the baseline (Week 0) visit. Results from a local
laboratory may be used for this assessment.

- 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.

- 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.

- Use of other drugs known to influence calcium and bone metabolism, such as calcitonin,
fluoride tablets, or cinacalcet hydrochloride, within the prohibited period.

- Use of oral bisphosphonates within the previous 6 months or intravenous bisphosphonate
preparations within the previous 24 months before screening.

- Nonhypocalcemic seizure disorder with a history of a seizure within the previous 6
months before screening. Participants with a history of seizures that occur in the
setting of hypocalcemia are allowed.

- The participant 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
implan


Age minimum: 18 Years
Age maximum: 85 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hypoparathyroidism

Intervention(s)

Biological: Placebo

Biological: rhPTH(1-84)

Primary Outcome(s)

Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Subscale Score at Week 26 [Time Frame: Baseline, Week 26]

Secondary Outcome(s)

Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Impact Subscale Score at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HPT-SD) Impact Items Score at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Item Anxiety (item 8) Score at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Change (PGI-C) at Week 26 [Time Frame: Baseline, Week 26]

Number of Participants With Albumin-corrected Serum Calcium Control at Week 26 [Time Frame: Week 26]

Number of Participants With Response at Week 26 [Time Frame: Baseline to Week 26]

Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24 [Time Frame: Baseline, Week 24]

Change From Baseline in Mental Component Summary (MCS) Score of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 [Time Frame: Baseline, Week 26]

Number of Participants who Achieve Composite Criteria for Albumin-corrected Serum Calcium Concentration, Vitamin D Dose and Oral Calcium Supplement Dose at Week 26 [Time Frame: Baseline to Week 26]

Change From Baseline in 24-hour Urine Calcium Excretion at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Doses of Active Vitamin D and Calcium Supplements at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Item Sadness or Depression (Item 9) Score at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in At-Home Neurocognitive Assessment Scores at Week 24 [Time Frame: Baseline, Week 24]

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Physical Component Summary (PCS) Derived From 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in the Most Bothersome Symptom Score at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Hypoparathyroidism (WPAI:Hypoparathyroidism) Score at Week 26 [Time Frame: Baseline, Week 26]

Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Time Frame: From start of study drug administration up to end of study (Week 30)]

Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Bone Turnover Markers at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Score at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HPT-SD) Symptom Items Score at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Severity (PGI-S) at Week 26 [Time Frame: Baseline, Week 26]

Change From Baseline in Serum Phosphate Level at Week 26 [Time Frame: Baseline, Week 26]

Secondary ID(s)

2017-000284-32

SHP634-401

Source(s) of Monetary Support

Please refer to primary and secondary sponsors