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

NCT ID: NCT03324880

Last Updated: 2023-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-24
• Study Completion Date: 2022-05-19

Brief Summary

Recombinant human parathyroid hormone, also known as if rhPTH(1-84), is a medicine to treat people with Hypothyroidism. The main aim of this study is to learn if rhPTH(1-84) can improve symptoms in adults with hypoparathyroidism.

In this study, participants will receive 1 of 2 treatments: rhPTH(1-84) or a placebo. A placebo looks like the medicine being studied but does not have medicine in it. In this study, the placebo will be a standard treatment which is either active Vitamin D, or active Vitamin D with calcium. Active Vitamin D is a form of vitamin D that has a faster effect on the body. These treatments will be given as a daily injection just under the skin. Participants will not know which treatment they received, nor will their study doctors. This is to help make sure the results are more reliable. All participants will also take active vitamin D and calcium supplements during treatment.

Participants will record their symptoms in a tool called the hypoparathyroidism symptom diary. This tool is used to assess symptoms and their impact and will give an overall score for each participant.

The study doctors will also check for side effects from the study treatments.

After treatment, researchers will check if there is any difference in the diary scores between the 2 treatment groups. A difference in score means there is a difference in symptoms and their impact. From this, researchers will learn if symptoms have improved for participants treated with rhPTH(1-84) compared with those treated with placebo.

Detailed Description

24 SEPTEMBER 2020: The temporary enrollment stop of new patients into this study due to the COVID-19 pandemic has been lifted in one or more countries, and the study is now again enrolling new patients. However, some countries/sites may still have paused the enrollment of new patients due to the pandemic.

20 APRIL 2020: Enrollment of new patients into this study has been paused due to the COVID-19 situation. The duration of this pause is dependent on the leveling and control of the COVID-19 pandemic.

Conditions

Hypoparathyroidism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Participants received placebo matched to rhPTH (1-84) as subcutaneous (SC) injection once daily (QD) with active vitamin D and calcium supplements up to 31.3 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Placebo QD SC injection.

rhPTH (1-84)

Participants received rhPTH (1-84) 50 microgram (mcg) SC injection QD, titrated within the dose range of 25-100 mcg QD as an adjunctive treatment with active vitamin D and calcium supplements based on metabolic response up to 32 weeks.

Group Type: EXPERIMENTAL

rhPTH (1-84)

Intervention Type: BIOLOGICAL

rhPTH (1-84) SC injection.

Interventions

rhPTH (1-84)

rhPTH (1-84) SC injection.

Intervention Type: BIOLOGICAL

Placebo

Placebo QD SC injection.

Intervention Type: BIOLOGICAL

Eligibility 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 implant radiation therapy involving the skeleton.
• Any disease or condition that, in the opinion of the investigator, may require treatment or make the participant 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.
• Pregnant or lactating women.
• Known or suspected intolerance or hypersensitivity to the investigational product, closely-related compounds, or any of the stated ingredients.
• History of diagnosed drug or alcohol dependence within the previous 3 years.
• Poorly controlled short bowel syndrome, bowel resection, tropical sprue, celiac disease, ulcerative colitis, and Crohn disease.
• Chronic or severe cardiac disease including but not limited to heart failure (according to the New York Heart Association classification Class II to Class IV) (Dolgin and NYHA, 1994), arrhythmias, bradycardia (resting heart rate <50 beats/minute).
• History of cerebrovascular accident.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

University of Chicago

Chicago, Illinois, United States

Michigan Bone and Mineral Clinic

Detroit, Michigan, United States

Mayo Clinic - PPDS

Rochester, Minnesota, United States

Physicians East PA

Greenville, North Carolina, United States

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

UZ Gent

Ghent, Oost-Vlaanderen, Belgium

UZ Leuven

Leuven, Vlaams Brabant, Belgium

Nova Scotia Health Authority (Capital District Health Authority)

Halifax, Nova Scotia, Canada

Bone Research and Education Centre

Oakville, Ontario, Canada

CHU de Quebec-Universite Laval

Québec, , Canada

Eastern Health - Health Sciences Center- General Hospital

St. John's, , Canada

Aarhus Universitetshospital

Aarhus N, Central Jutland, Denmark

Odense Universitetshospital

Odense C, , Denmark

CHU Angers

Angers, , France

Hopital Jean Minjoz

Besançon, , France

CHU Bicêtre

Le Kremlin-Bicêtre, , France

CHRU Lille

Lille, , France

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, Saxony, Germany

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

Universita di Firenze, Dipartimento di Chirurgia e Medicina Traslazionale (DCMT)

Florence, , Italy

Università Campus Bio Medico Di Roma

Roma, , Italy

VU Medisch Centrum

Amsterdam, North Holland, Netherlands

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Haukeland Universitetssykehus

Bergen, , Norway

Oslo Universitetssykehus HF Rikshospitalet

Oslo, , Norway

Oslo Universitetssykehus Aker

Oslo, , Norway

Centro Hospitalar E Universitário de Coimbra EPE

Coimbra, , Portugal

Unidade Local de Saúde de Matosinhos SA

Matosinhos Municipality, , Portugal

Centro Hospitalar de São João, E.P.E.

Porto, , Portugal

C.H. Regional Reina Sofia - PPDS

Córdoba, Córdoba, Spain

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Ninewells Hospital - PPDS

Dundee, Dundee City, United Kingdom

Norfolk and Norwich University Hospital

Norwich, Norfolk, United Kingdom

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Leicester Royal Infirmary

Leicester, , United Kingdom

Manchester Royal Infirmary - PPDS

Manchester, , United Kingdom

Countries

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

References

Brandi ML, Vokes T, Appelman-Dijkstra NM, Ayodele O, Decallonne B, de Jongh R, Diaz-Curiel M, Fraser W, Finkelman RD, Heck A, Ing SW, Kamenicky P, Khan AA, Kovacs CS, Lapauw B, Leese G, Mantovani G, Martinez Diaz-Guerra G, Masi L, Melo M, Palermo A, Reddy NL, Rejnmark L, Tokareva E, Vantyghem MC, Wang S, Warren M, Yan B. rhPTH(1-84) for hypoparathyroidism: a randomized study of patient-reported outcomes. Eur J Endocrinol. 2025 Jul 31;193(2):310-319. doi: 10.1093/ejendo/lvaf148.

Reference Type: DERIVED

PMID: 40711996 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b5fda4db2bf003ab4711e

To obtain more information on the study, click here/on this link

Other Identifiers

2017-000284-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SHP634-401

Identifier Type: -

Identifier Source: org_study_id