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HypoparathyroidismPhase 3NCT03364738

Safety and Efficacy Study of rhPTH(1-84) in Subjects With Hypoparathyroidism

A Phase 3 study testing rhPTH(1-84) in people with Hypoparathyroidism, run by Shire at 10 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study is open to adults with hypoparathyroidism who complete the SHP634-101 study (PARALLAX Study). The purpose of this study is to see if rhPTH(1-84) is safe and effective in adults with hypoparathyroidism who previously participated in the SHP634-101 study. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hypoparathyroidism
What is being tested?
rhPTH(1-84)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
10 sitesin 4 countries
Study dates
26 Sep 2018to 14 Apr 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • An understanding, ability, and willingness to fully comply with study procedures and restrictions
  • Ability to voluntarily provide written, signed, and dated informed consent to participate in the study.
  • Previously completed the SHP634-101 (NCT02781844) study, including the 30-day follow-up.
  • Male or non-pregnant, non-lactating female subjects who agree to comply with applicable contraceptive requirements of the protocol or females of non-childbearing potential.

Who cannot join

  • Received investigational study drug, aside from that received in study SHP634-101 (NCT02781844), within 3 months prior to the screening visit.
  • Presence or history of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine (with exception of the condition under study), or neurologic system(s) or psychiatric disease, that in the opinion of the investigator, would make the subject unsuitable for this study.
  • Received parathyroid hormone (PTH), PTH analog, or parathyroid hormone fragment 1-34 [PTH(1-34)] treatment within the last 30 days from the screening visit.
  • Subjects with a history of parathyroid hormone intolerance, based on investigator determination.
  • Any disease that might affect calcium metabolism or calcium-phosphate homeostasis as determined by the investigator other than hypoparathyroidism, including but not limited to, active hyperthyroidism; poorly controlled insulin-dependent diabetes mellitus or type 2 diabetes mellitus; severe and chronic cardiac, liver or renal disease; Cushing's syndrome; neuromuscular disease such as rheumatoid arthritis; myeloma; pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy, bone metastases or a history of skeletal malignancies; primary or secondary hyperparathyroidism; a history of parathyroid carcinoma; hypopituitarism, acromegaly; or multiple endocrine neoplasia types 1 and 2 .
  • Subjects who are at increased baseline risk for osteosarcoma such as subjects with Paget's disease of bone or unexplained elevations of alkaline phosphatase, young adult subjects with open epiphyses, subjects with hereditary disorders predisposing to osteosarcoma or subjects with a prior history of external beam or implant radiation therapy involving the skeleton.
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  • Use of the following medications prior to administration of investigational product within:
  • 30 days-loop diuretics, lithium, systemic corticosteroids (medical judgment is required by the investigator. Primarily high doses of systemic corticosteroids [example (eg), prednisone] should be excluded. Stable doses of hydrocortisone [eg, as treatment for Addison's disease] may be acceptable).
  • 3 months-cinacalcet hydrochloride
  • 6 months-fluoride tablets, oral bisphosphonates, methotrexate, growth hormone, digoxin
  • 12 months-intravenous bisphosphonates, drug or alcohol abuse, as determined by the investigator
  • Presence of any clinically significant results from laboratory tests, vital signs assessments, or electrocardiograms (ECG), that in the opinion of the investigator, would make the subject unsuitable for this study.
  • Any medical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for this study.
  • History of a clinically significant illness during the 4 weeks prior to dosing, that in the opinion of the investigator, would make the subject unsuitable for this study.
  • History of any clinically significant surgery or procedure within 8 weeks of first dose, as determined by the investigator or expected to undergo a major surgical procedure during the trial.
  • History of an allergic response(s) to PTH, PTH analogs, or PTH(1-34), or other clinically significant allergies, that in the opinion of the investigator, would make the subject unsuitable for this study.

Trial locations and contacts

10 sites in 4 countries.

10 sites in 4 countries

United States5 sites
  • Ohio State University

    Columbus, Ohio, 43210

  • University of Kentucky Medical Center

    Lexington, Kentucky, 40536

  • Crescent City Clinical Research Center, LLC

    Metairie, Louisiana, 70006

  • Thomas Jefferson University, Jefferson Rheumatology Associates

    Philadelphia, Pennsylvania, 19107-6810

  • Northern Nevada Endocrinology - Lisa Abbott MD

    Reno, Nevada, 89511-2060

Other trials in United States

Canada2 sites
  • Bone Research and Education Centre

    Oakville, Ontario, L6M 1M1

  • CHU de Quebec-Universite Laval

    Québec, G1V 4G2

Other trials in Canada

Hungary2 sites
  • Semmelweis Egyetem

    Budapest, 1083

  • Pecsi Tudomanyegyetem, I. sz. Belgyogyaszati Klinika

    Pécs, 7624

Other trials in Hungary

Denmark1 site
  • Aarhus Universitetshospital

    Aarhus N, 8200

Other trials in Denmark

About this study

Official title: An Open-label Study Investigating the Safety and Efficacy of rhPTH(1-84) in Subjects With Hypoparathyroidism

This study is open to adults with hypoparathyroidism who complete the SHP634-101 study (PARALLAX Study). The purpose of this study is to see if rhPTH(1-84) is safe and effective in adults with hypoparathyroidism who previously participated in the SHP634-101 study. All participants enrolled in this study will receive rhPTH(1-84) once-daily for 52 weeks via an injection.

Patients who complete the SHP634-101 study will have the option to screen for this extension study.

Being tested
rhPTH(1-84)
Medical subject headings
Hypoparathyroidism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rhPTH(1-84)Biological

    Participants will receive rhPTH(1-84) SC injection in the thigh (alternate thigh every day) QD.

Study groups in NCT03364738
Study groupRoleWhat they receive
rhPTH(1-84)ExperimentalParticipants will receive rhPTH(1-84) subcutaneous (SC) injection in the thigh (alternate thigh every day) once daily (QD) of an escalating dose from 50 microgram (mcg) to a maximum of 100 mcg increased in increments of 25 mcg no more frequently than every 2 to 4 weeks, with the goal of achieving or maintaining albumin-corrected serum calcium (ACSC) levels in the range of 2-2.25 millimoles per liter (mmol/L) (8.0-9.0 milligrams per deciliter [mg/dL]). Once a participant achieves a stable ACSC (2-2.25 mmol/L [8.0-9.0mg/dL]) and has minimized supplement doses, they will be maintained at that dose of rhPTH(1-84). If ACSC is greater than (>) 2.25 mmol/L (>9.0 mg/dL), a starting dose of 25 mcg will be administered.
Receives: Biological: rhPTH(1-84)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Who Achieved Total Albumin-corrected Serum Calcium (ACSC) Values Greater Than or Equal to (>=) to the Range of 7.5 mg/dL (1.875 mmol/L) and Less Than or Equal to (<=) Upper Limit of Normal (ULN) at Week 24

    Percentage of participants who achieved ACSC values >= to range of 1.875 mmol/L and <= ULN at Week 24 was reported.

    Measured: At Week 24

  2. Percentage of Participants With Total ACSC Values >= to the Range of 7.5 mg/dL (1.875 mmol/L) and <=ULN at Week 52 (End-of-treatment [EOT])

    Percentage of participants who achieved ACSC values >= to range of 1.875 mmol/L and <= ULN at Week 52 (EOT) was reported.

    Measured: At Week 52 (EOT)

  3. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

    An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, and is an important medical event. TEAEs were defined as AEs with a start date on or after the first dose of investigational product or a start date before the date of the first dose of investigational product that increased in severity or after the date of the first dose.

    Measured: From start of study drug administration to end of study (Week 56)

  4. Number of Participants With Clinically Significant Change in Clinical Laboratory Values

    Clinical laboratory assessment included hematology, serum chemistry, urine chemistry and urinalysis. Clinical significance was judged by the investigator based upon the out of range values of standard range set for each parameter. Any changes in clinical laboratory results which were deemed clinically significant by the investigator was reported.

    Measured: From start of study drug administration to end of study (Week 56)

  5. Number of Participants With Clinically Significant Change in Vital Sign

    Vital sign parameters included: temperature, pulse rate, respiration rate, systolic and diastolic blood pressure. Clinical significance was judged by the investigator based upon the out of range values of standard range set for each parameter. Any changes in vital signs which were deemed clinically significant by the investigator was reported.

    Measured: From start of study drug administration to end of study (Week 56)

  6. Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters

    Twelve-lead ECGs was performed in triplicate with a minimum 2-minute gap between traces. The participant rested in the supine position for at least 5 minutes before collecting the ECG. Assessment of ECG parameters included: heart rate, RR interval, PR interval, QRS interval, QT interval, and QTc interval. Clinical significance was judged by the investigator based upon the out of range values of standard range set for each parameter. Any change in ECG assessments which were deemed clinically significant by the investigator was reported.

    Measured: From start of study drug administration to end of study (Week 56)

  7. Number of Participants With Clinically Significant Change in Estimated Glomerular Filtration Rate (eGFR) Values

    eGFR was calculated using the chronic kidney disease epidemiology (CDK-epi) formula. Clinical significance was judged by the investigator based upon the out of range values of standard range set for parameter. Any change in eGFR assessments which were deemed clinically significant by the investigator was reported.

    Measured: From start of study drug administration to end of study (Week 56)

  8. Number of Participants With Clinically Significant Change in Serum Creatinine Value

    eGFR was assessed by measuring serum creatinine. Serum creatinine level was obtained directly from laboratory results. Clinical significance was judged by the investigator based upon the out of range values of standard range set for parameter. Any change in serum creatinine assessments which were deemed clinically significant by the investigator was reported.

    Measured: From start of study drug administration to end of study (Week 56)

  9. Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 24

    Number of participants with positive anti-parathyroid hormone antibodies at Week 24 was reported.

    Measured: Week 24

  10. Number of Participants With Positive Anti-Parathyroid Hormone Antibodies at Week 52 (EOT)

    Number of participants with positive anti-parathyroid hormone antibodies at Week 52 (EOT) was reported.

    Measured: Week 52 (EOT)

Secondary outcomes (11)
  1. Change From Baseline in Albumin Corrected Serum Calcium (ACSC) Concentration at Weeks 24 and 52 (EOT)

    Change from baseline in ACSC concentration at Weeks 24 and 52 (EOT) was reported.

    Measured: Baseline, Weeks 24 and 52 (EOT)

  2. Change From Baseline in Serum Phosphate Concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)

    Change from baseline in serum phosphate concentration at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) was reported.

    Measured: Baseline, Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)

  3. Change From Baseline in ACSC-phosphate Product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)

    Change from baseline in ACSC-phosphate product at Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT) was reported. Here "mmol^2/L^2" is abbreviated as millimoles square per liter square.

    Measured: Baseline, Weeks 4, 8, 16, 24, 32, 40 and 52 (EOT)

  4. Change From Baseline in 24-hour Urine Calcium Excretion at Weeks 16, 32 and 52 (EOT)

    Change from baseline in 24-hour urine calcium excretion at Weeks 16, 32 and 52 (EOT) was reported.

    Measured: Baseline, Weeks 16, 32 and 52 (EOT)

  5. Percentage Change From Baseline in Prescribed Supplemental Oral Calcium Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (End of Study [EOS])

    Percentage change from baseline in prescribed supplemental oral calcium dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) were reported.

    Measured: Baseline and at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS)

  6. Percentage Change From Baseline in Prescribed Supplemental Active Vitamin D Dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS)

    Percentage change from baseline in prescribed supplemental oral calcium dose at Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS) were reported.

    Measured: Baseline, Weeks 4, 8, 16, 24, 32, 40, 52 (EOT) and 56 (EOS)

  7. Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase at Weeks 8, 24 and 52 (EOT)

    Percentage change from baseline in serum bone-specific alkaline phosphatase at Weeks 8, 24 and 52 (EOT) was reported.

    Measured: Baseline, Weeks 8, 24 and 52 (EOT)

  8. Percentage Change From Baseline in Serum Osteocalcin at Weeks 8, 24 and 52 (EOT)

    Percentage change from baseline in serum osteocalcin at Weeks 8, 24 and 52 (EOT) was reported.

    Measured: Baseline, Weeks 8, 24 and 52 (EOT)

  9. Percentage Change From Baseline in Procollagen 1 N-Terminal Propeptide at Weeks 8, 24 and 52 (EOT)

    Percentage change from baseline in procollagen 1 N-terminal propeptide at Weeks 8, 24 and 52 (EOT) was reported.

    Measured: Baseline, Weeks 8, 24 and 52 (EOT)

  10. Percentage Change From Baseline in Type I Collagen C-Telopeptides at Weeks 8, 24 and 52 (EOT)

    Percentage change from baseline in type I collagen C-telopeptides at Week 8, 24 and 52 (EOT) was reported.

    Measured: Baseline, Weeks 8, 24 and 52 (EOT)

  11. Percentage Change From Baseline in Type I Collagen N-Telopeptides at Weeks 8, 24 and 52 (EOT)

    Percentage change from baseline in type I collagen N-telopeptides at Week 8, 24 and 52 (EOT) was reported.

    Measured: Baseline, Weeks 8, 24 and 52 (EOT)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2017
  2. Study start26 Sep 2018
  3. Primary completion14 Apr 2020
  4. Study completion14 Apr 2020

Why it stopped: The study was terminated due to Takeda commercial Natpara recall.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03364738
Sponsor's protocol ID
SHP634-404
Other IDs
2017-003067-36, 2017
Status last verified
May 2021
First submitted
20 Nov 2017
Last updated
7 Oct 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Publications

  • Khan AA, Abbott LG, Ahmed I, Ayodele O, Gagnon C, Finkelman RD, Mezosi E, Rejnmark L, Takacs I, Yin S, Ing SW. Open-label extension of a randomized trial investigating safety and efficacy of rhPTH(1-84) in hypoparathyroidism. JBMR Plus. 2024 Jan 5;8(3):ziad010. doi: 10.1093/jbmrpl/ziad010. eCollection 2024 Mar.

    PubMed 38741607

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing rhPTH(1-84) in people with Hypoparathyroidism, run by Shire at 10 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Canada, Hungary, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Achieved Total Albumin-corrected Serum Calcium (ACSC) Values Greater Than or Equal to (>=) to the Range of 7.5 mg/dL (1.875 mmol/L) and Less Than or Equal to (<=) Upper Limit of Normal (ULN) at Week 24 (time frame: At Week 24). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03364738, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2022.

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