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

NCT03324880 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: SHP634-4012017-000284-32
• Study Type: interventional
• Target: 93
• Locations: 13 countries
• Sites: 40

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.

Conditions

Hypoparathyroidism

Keywords

rhPTH[1-84); Parathyroid hormone; Hypocalcemia; Hypoparathyroidism

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Subscale Score at Week 26

  The HypoPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7), anxiety (item 8), sadness or depression (item 9) and impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4; for items 10-13, it ranges from Not at all=0 to Very much=2. An item score was computed by taking the average of the daily item response over the 14-day period immediately before the visit. If data were not available for at least 4 out of 7 days during both 7-day periods within the 14-day period, the individual item score was set to missing. The symptom subscale score was computed as the average of symptom items 1-7 scores with more than 3 of the 7 symptom item scores were non-missing. Negative change in scores indicates improvement. A mixed model for repeated measures (MMRM) was used for analysis.

  Baseline, Week 26

Secondary Outcomes (28)

• Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 26

  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

  Baseline, Week 26

• Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Subscale Score at Week 26

  Baseline, Week 26

• Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Items Score at Week 26

  Baseline, Week 26

• Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Anxiety (Item 8) Score at Week 26

  Baseline, Week 26

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Biological: Placebo

rhPTH (1-84)

EXPERIMENTAL

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.

Biological: rhPTH (1-84)

Interventions

rhPTH (1-84) BIOLOGICAL

rhPTH (1-84) SC injection.

rhPTH (1-84)

Placebo BIOLOGICAL

Placebo QD SC injection.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (40)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Michigan Bone and Mineral Clinic

Detroit, Michigan, 48236, United States

Location

Mayo Clinic - PPDS

Rochester, Minnesota, 55905, United States

Location

Physicians East PA

Greenville, North Carolina, 27834, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43203, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UZ Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

UZ Leuven

Leuven, Vlaams Brabant, 3000, Belgium

Location

Nova Scotia Health Authority (Capital District Health Authority)

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Bone Research and Education Centre

Oakville, Ontario, L6M 1M1, Canada

Location

CHU de Quebec-Universite Laval

Québec, G1J 1Z4, Canada

Location

Eastern Health - Health Sciences Center- General Hospital

St. John's, A1B3V6, Canada

Location

Aarhus Universitetshospital

Aarhus N, Central Jutland, 8200, Denmark

Location

Odense Universitetshospital

Odense C, 5000, Denmark

Location

CHU Angers

Angers, 49933, France

Location

Hopital Jean Minjoz

Besançon, 25030, France

Location

CHU Bicêtre

Le Kremlin-Bicêtre, 94275, France

Location

CHRU Lille

Lille, 59000, France

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, Saxony, 1307, Germany

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

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

Florence, 50139, Italy

Location

Università Campus Bio Medico Di Roma

Roma, 128, Italy

Location

VU Medisch Centrum

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, 2300 RC, Netherlands

Location

Haukeland Universitetssykehus

Bergen, 5021, Norway

Location

Oslo Universitetssykehus HF Rikshospitalet

Oslo, 372, Norway

Location

Oslo Universitetssykehus Aker

Oslo, N-0514, Norway

Location

Centro Hospitalar E Universitário de Coimbra EPE

Coimbra, 3000-075, Portugal

Location

Unidade Local de Saúde de Matosinhos SA

Matosinhos Municipality, 4464-513, Portugal

Location

Centro Hospitalar de São João, E.P.E.

Porto, 4200-319, Portugal

Location

C.H. Regional Reina Sofia - PPDS

Córdoba, Córdoba, Spain

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Sahlgrenska Universitetssjukhuset

Gothenburg, 41345, Sweden

Location

Ninewells Hospital - PPDS

Dundee, Dundee City, DD1 9SY, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, Norfolk, NR4 7UY, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Manchester Royal Infirmary - PPDS

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40711996 DERIVED

Related Links

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

MeSH Terms

Conditions

Hypoparathyroidism; Hypocalcemia

Condition Hierarchy (Ancestors)

Parathyroid Diseases; Endocrine System Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Water-Electrolyte Imbalance

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: October 30, 2017
• Study Start: January 24, 2018
• Primary Completion: May 19, 2022
• Study Completion: May 19, 2022
• Last Updated: June 9, 2023
• Results First Posted: June 9, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

GB (5); FR (4); DK (2); IT (3); DE (1); NL (2); US (6); NO (3); BE (2); CA (4); PT (3); ES (4); SE (1)