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A Study of Extended Use of Recombinant Human Parathyroid Hormone (rhPTH(1-84)) in Hypoparathyroidism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02910466
Recruitment Status : Active, not recruiting
First Posted : September 22, 2016
Last Update Posted : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

Brief Summary:
Chronic hypoparathyroidism is a life-long and irreversible disease for which the chronic administration of rhPTH(1-84) is a potential treatment option. The group of participants in the AAAE0544 core study has been taking rhPTH(1-84) for the treatment of hypoparathyroidism for up to 11 years. This study is designed to extend this experience and gain knowledge about how safe and effective rhPTH(1-84) is in participants with hypoparathyroidism over a long-term duration.

Condition or disease Intervention/treatment Phase
Chronic Hypoparathyroidism Hypoparathyroidism Drug: rhPTH(1-84) Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 4, Open-Label, Single-Center Clinical Study of Extended Use of rhPTH(1-84) in Hypoparathyroidism
Actual Study Start Date : December 9, 2016
Estimated Primary Completion Date : July 30, 2021
Estimated Study Completion Date : July 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: rhPTH(1-84)
Participants will receive 25, 50, 75, and 100 microgram (mcg) of rhPTH(1-84) subcutaneous injection to the thigh via a multidose pen injector device once daily for 48 months. The dose will be individualized based on albumin-corrected serum calcium (ACSC) and 24-hour calcium urinary excretion to achieve a serum calcium level in the lower half of the normal range.
Drug: rhPTH(1-84)
Participants will receive 25, 50, 75, and 100 microgram (mcg) of rhPTH(1-84) subcutaneous injection to the thigh via a multidose pen injector device once daily for 48 months. The dose will be individualized based on Albumin-corrected Serum Calcium (ACSC) and 24-hour calcium urinary excretion to achieve a serum calcium level in the lower half of the normal range.




Primary Outcome Measures :
  1. Change From Baseline in Concentration of Albumin-corrected Serum Calcium (ACSC) [ Time Frame: Baseline to every 6 months for approximately 48 months ]
    Change from baseline in concentration of ACSC will be assessed.


Secondary Outcome Measures :
  1. Proportion of Participants who Achieve Albumin-corrected Serum Calcium (ACSC) Values Above, Below, or in the Range of 7.5 Milligrams per Decilitre (mg/dL)-Upper Limit of Normal (ULN) [ Time Frame: Baseline up to 48 months ]
    Proportion of participants who achieve ACSC values above, below, or in the range of 7.5mg/dL-ULN will be assessed.

  2. Change From Baseline in Urinary Calcium Excretion [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    Change from baseline in urinary calcium excretion will be assessed.

  3. Change From Baseline in Concentration of Serum Phosphate [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    Change from baseline in concentration of serum phosphate will be assessed.

  4. Change From Baseline in Dose of Calcium supplement [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    Change from baseline in dose of calcium supplement will be assessed.

  5. Change From Baseline in Dose of Active Vitamin D supplement [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    Change from baseline in dose of active vitamin D supplement will be assessed.

  6. Change From Baseline in Hypoparathyroidism Symptoms Measured by the Hypoparathyroidism Symptom Diary (HPT-SD) [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    The HPT-SD is a 13-item patient-reported outcomes instrument that consists of the following items: symptom subscale (items 1-7); anxiety (item 8); sadness and depression (item 9); impact subscale (items 10-13). For items 1-9, the individual score ranges from None=0 to Very severe=4 and for items 10-13, it ranges from Not at all=0 to Very much=2. For symptom subscale score, the average score of the symptom items 1-7 will be calculated.

  7. Change From Baseline in Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) Assessment [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    Change from baseline in FACT-Cog assessment will be assessed. The FACT-Cog assessment is a 37-item tool. The items are rated using a 5-point Likert scale ranged 0 from 4. It includes 4 subscales: 2 subscales ranged as following: 0 (never), 1 (About once a week), 2 (two to three times a week), 3 (Nearly every day) and 4 (several times a day): Perceived cognitive impairments subscale and comments from others subscale and two others subscale ranged as following: 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit) and 4 (very much): Perceived cognitive abilities and impact on quality of life subscales. The total score is obtained with the sum of these 4 subscales.

  8. Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) (Fatigue Scale) [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    The FACIT fatigue questionnaire contains 13 fatigue-related questions. The responses to the 13 items on the FACIT fatigue questionnaire are each measured on a 4-point Likert scale. Thus, the total score ranges from 0 to 52. High scores represent less fatigue.

  9. Change From Baseline in Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    The HADS is a 14-item scale that generates ordinal data. Seven of the items relate to anxiety and seven relate to depression. The scale is designed to avoid reliance on aspects of conditions that are also common somatic symptoms of illness. Each item on the questionnaire is scored from 0-3, therefore, a person can score between 0 and 21 for either anxiety or depression. For each of the two subscores, if a participant obtain a score ranged from: 0 to 7, he is considered as "normal"; 8-10 = Borderline abnormal (borderline case) and 11-21 = Abnormal (case).

  10. Change From Baseline in Health-related Quality-of-life Measured With 36-item Short Form Health (SF-36) Survey [ Time Frame: Baseline, 12, 24, 36 and 48 months ]
    The SF-36 is a validated questionnaire that questions participants about perceived physical and mental health and function. The SF-36 consists of 8 scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight; the lower the score the more disability. The higher the score the less disability that is (ie), a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections included in the SF-36 assessment are vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health.

  11. Change From Baseline in Concentration of Bone Turnover Markers [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    Change from baseline in concentration of bone turnover markers including, but not limited to, serum carboxy-terminal 4 telopeptide of type I collagen [s-CTX], procollagen type I amino-terminal propeptide [P1NP], osteocalcin, bone specific alkaline phosphatase [BSAP], TRAP-5b, and sclerostin will be assessed.

  12. Change From Baseline in Bone Architecture Evaluated Using Dual-energy X-ray Absorptiometry (DXA) [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    Change from baseline in bone architecture will be assessed by using DXA. The DXA scans will evaluate bone mineral density and T-scores of the lumbar spine (vertebra L1-L4), hip (total and femoral neck), and ⅓ distal radius (arm).

  13. Change From Baseline in Bone Architecture Evaluated Using High-resolution Peripheral Quantitative Computerized Tomography (HRpQCT) [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    Change from baseline in bone architecture will be assessed by using HRpQCT. The HRpQCT analyses includes Individual Trabecula Segmentation (ITS) analysis and finite element modeling.

  14. Change From Baseline in Bone Histology (Biopsy) [ Time Frame: Baseline, 6, 12, 18, 24, 30, 36, 42 and 48 months ]
    Change from baseline in bone histology (biopsy) will be assessed.



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Participants that are currently or previously enrolled in the core study (AAAE0544 [NCT01199614]) and have maintained uninterrupted therapy with recombinant human parathyroid hormone (rhPTH(1-84)) (transient interruptions of up to 1 month continuously off treatment may be allowed).
  • Signed and dated informed consent form (ICF).
  • Adult men and women 18 to 85 years of age.
  • History of hypoparathyroidism for at least 12 months prior to rhPTH(1-84) treatment, defined by the requirement for supplemental calcium and/or active vitamin D to maintain serum calcium along with an undetectable or insufficient Parathyroid hormone (PTH) concentration.
  • Able to perform daily subcutaneous (SC) self-injections of study medication (or have designee perform injection).
  • Willingness and ability to understand and comply with the protocol. Women must agree to pregnancy testing and acceptable methods of contraception, as detailed in the protocol.

Exclusion Criteria

  • The participant is treated or has been treated with any investigational drug, aside from rhPTH(1-84), within 30 days of consent.
  • As assessed by the investigator, the participant has any safety or medical issues that contraindicate participation in the study.
  • The participant and/or the participant's parent(s) or legally-authorized representative(s) are unable to understand the nature, scope, and possible consequences of the study.
  • The participant is unable to comply with the protocol, example, 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 is pregnant or lactating.
  • Participants who are at increased baseline risk for osteosarcoma such as participant with Paget's disease of bone or unexplained new elevations of alkaline phosphatase, participants with hereditary disorders predisposing to osteosarcoma or participants with a prior history of external beam or implant radiation therapy involving the skeleton.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02910466


Locations
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United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Shire
Investigators
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Study Director: Study Director Shire

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Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02910466     History of Changes
Other Study ID Numbers: SHP634-402
First Posted: September 22, 2016    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hypoparathyroidism
Parathyroid Diseases
Endocrine System Diseases
Parathyroid Hormone
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs