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A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Daily in Adults With Hypoparathyroidism (PaTHway)

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ClinicalTrials.gov Identifier: NCT04701203
Recruitment Status : Active, not recruiting
First Posted : January 8, 2021
Last Update Posted : August 2, 2021
Sponsor:
Information provided by (Responsible Party):
Ascendis Pharma A/S ( Ascendis Pharma Bone Diseases A/S )

Brief Summary:
During the first 26 weeks of the trial, participants will be randomly assigned to one of two groups: one group will receive TransCon PTH and one group will receive placebo. All subjects will start with a fixed dose of study drug and will be individually and progressively titrated to an optimal dose over a 10 week period, followed by an individualized dosing period up to 16 weeks. TransCon PTH or placebo will be administered as a subcutaneous injection using a pre-filled injection pen. Neither trial participants nor their doctors will know who has been assigned to each group. After the 26 weeks, participants will continue in the trial as part of a long-term extension study. During the extension, all participants will receive TransCon PTH, with the dose adjusted to their individual needs. This is a global trial that will be conducted in, but not limited to, the United States, Canada, Germany, and Denmark.

Condition or disease Intervention/treatment Phase
Hypoparathyroidism Endocrine System Diseases Parathyroid Diseases Combination Product: TransCon PTH Combination Product: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, placebo controlled, parallel group with subjects randomized into two treatment groups (3:1): TransCon PTH at a starting dose of 18 mcg/day, and placebo for TransCon PTH
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: PaTHway TRIAL: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial, With an Open-Label Extension, Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Subcutaneously Daily in Adults With Hypoparathyroidism
Actual Study Start Date : February 16, 2021
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TransCon PTH
TransCon PTH at a starting dose of 18 mcg delivered once daily by subcutaneous injection
Combination Product: TransCon PTH
TransCon PTH drug product is supplied as a solution with a concentration of 0.3 mg PTH(1-34)/mL in a single-patient-use prefilled pen intended for subcutaneous injection.

Placebo Comparator: Placebo
Placebo for TransCon PTH delivered once daily by subcutaneous injection
Combination Product: Placebo
Placebo is supplied as a solution containing the formulation buffer for TransCon PTH in a single-patient-use prefilled pen intended for subcutaneous injection.




Primary Outcome Measures :
  1. Efficacy - Primary endpoint [ Time Frame: 26 weeks ]
    The proportion of subjects with albumin-adjusted sCa within the normal range, and Independence from active vitamin D, and Independence from therapeutic doses of calcium (i.e., taking calcium supplements ≤600 mg/day)


Secondary Outcome Measures :
  1. Efficacy - Key Secondary Endpoint [ Time Frame: 26 weeks ]
    The proportion of subjects with albumin-adjusted sCa within the normal range, and Independence from active vitamin D, and Independence from therapeutic doses of calcium (i.e., taking calcium supplements ≤600 mg/day), and Normal 24-hour urine calcium excretion or ≥ 50% reduction from baseline



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

Inclusion Criteria:

  1. Males and females, ≥18 years of age
  2. Subjects with postsurgical chronic HP, or auto-immune, genetic, or idiopathic HP for at least 26 weeks. Diagnosis of HP is established based on historic hypocalcemia in the setting of inappropriately low serum PTH levels
  3. Requirement for doses of SoC (e.g., calcitriol, alfacalcidol, calcium supplements) at or above a minimum threshold:

    • For countries other than Japan: requirement for a dose of calcitriol ≥0.5 μg/day, or alfacalcidol ≥1.0 μg/day and (elemental) calcium ≥800 mg/day (e.g., calcium citrate, calcium carbonate etc.) for at least 12 weeks prior to Screening. In addition, the dose of calcitriol, or alfacalcidol, or calcium should be stable for at least 5 weeks prior to Screening
    • For Japan: requirement for a dose of calcitriol ≥1.0 μg/day, or alfacalcidol ≥2.0 μg/day for at least 12 weeks prior to Screening. In addition, the dose of calcitriol or alfacalcidol should be stable for at least 5 weeks prior to Screening. In Japan only (due to local practice and dietary patterns), there is no requirement to exceed a minimum dose of calcium supplements
  4. Optimization of supplements prior to randomization to achieve the target serum levels of:

    • 25(OH) vitamin D levels of 20-80 ng/mL (49-200 nmol/L) and
    • Magnesium level in the normal range, or just below the normal range and
    • Albumin-adjusted or ionized sCa level in the normal range, or just below the normal range
  5. The subject demonstrates a 24-hour uCa excretion of ≥125 mg/24h (on a sample collected within 52 weeks prior to Screening or during the Screening Period)
  6. BMI 17- 40 kg/m2 at Screening
  7. If ≤25 years of age, radiological evidence of epiphyseal closure based on X-ray of nondominant wrist and hand
  8. Thyroid-stimulating hormone (TSH) within normal laboratory limits within the 6 weeks prior to Visit 1; if on suppressive therapy for a history of thyroid cancer, TSH level must be ≥0.2 mIU/mL
  9. If treated with thyroid hormone replacement therapy, the dose must have been stable for at least 5 weeks prior to Screening
  10. eGFR ≥30 mL/min/1.73 m2 during Screening
  11. Able to perform daily subcutaneous self-injections of study drug (or have a designee to perform injections) via a pre-filled injection pen
  12. Able and willing to provide written and signed informed consent in accordance with GCP

Exclusion Criteria:

  1. Impaired responsiveness to PTH (pseudohypoparathyroidism) which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia
  2. Any disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than HP, such as active hyperthyroidism; Paget disease of bone; severe hypomagnesemia; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus (HbA1C >9%, documented HbA1C result drawn within 12 weeks prior to Screening is acceptable); severe and chronic liver, or renal disease; Cushing syndrome; multiple myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy (other than low-risk well differentiated thyroid cancer or basal cell skin cancer); active hyperparathyroidism; parathyroid carcinoma within 5 years prior to Screening; acromegaly; or multiple endocrine neoplasia types 1 and 2
  3. High risk thyroid cancer within 2 years, requiring suppression of TSH <0.2 mIU/mL
  4. Use of loop diuretics, phosphate binders (other than calcium supplements), digoxin, lithium, methotrexate, biotin >30 μg/day, or systemic corticosteroids (other than as replacement therapy)
  5. Use of thiazide diuretic within 4 weeks prior to the 24-hour urine collection scheduled to occur within 1 week prior to Visit 1
  6. Use of PTH-like drugs (whether commercially available or through participation in an investigational trial), including PTH(1-84), PTH(1-34), or other N-terminal fragments or analogs of PTH or PTH-related protein, within 4 weeks prior to Screening
  7. Use of other drugs known to influence calcium and bone metabolism, such as calcitonin, fluoride tablets (>0.5 mg/day), strontium, or cinacalcet hydrochloride, within 12 weeks prior to Screening
  8. Use of osteoporosis therapies known to influence calcium and bone metabolism, i.e., bisphosphonate (oral or intravenous [IV]), denosumab, raloxifene, or romosozumab therapies within 2 years prior to Screening
  9. Non-hypocalcemic seizure disorder with a history of a seizure within 26 weeks prior to Screening
  10. Increased 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 substantial external beam or implant radiation therapy involving the skeleton
  11. Pregnant or lactating women
  12. Male who has a female partner who intends to become pregnant or is of childbearing potential and is unwilling to use adequate contraceptive methods during the trial
  13. Diagnosed drug or alcohol dependence within 3 years prior to Screening
  14. Disease processes that adversely affect gastrointestinal absorption, including but not limited to short bowel syndrome, significant small bowel resection, gastric bypass, tropical sprue, active celiac disease, active ulcerative colitis, active Crohn's disease, gastroparesis and AIRE gene mutations with malabsorption
  15. Chronic or severe cardiac disease within 26 weeks prior to Screening including but not limited to congestive heart failure, myocardial infarction, severe or uncontrolled arrhythmias, bradycardia (resting heart rate <48 beats/minute, unless chronic and asymptomatic), symptomatic hypotension or systolic BP <80 mm Hg or diastolic <40 mm Hg or poorly controlled hypertension (systolic BP >165 mm Hg or diastolic >95 mm Hg). In the absence of a prior history of hypertension, an isolated BP >165/95 in the setting of white coat hypertension/anxiety may not be exclusionary and a measurement can be repeated prior to randomization
  16. Cerebrovascular accident within 5 years prior to Screening
  17. Within 26 weeks prior to Screening: acute colic due to nephrolithiasis, or acute gout. Subjects with asymptomatic renal stones are permitted
  18. Participation in any other interventional trial in which receipt of investigational drug or device occurred within 8 weeks (or within 5.5 times the half-life of the investigational drug (whichever comes first) prior to Screening
  19. Any disease or condition that, in the opinion of the investigator, may require treatment or make the subject unlikely to fully complete the trial, or any condition that presents undue risk from the investigational product or procedures, including treated malignancies that are likely to recur within the approximate 3.5-year duration of the trial
  20. Known allergy or sensitivity to PTH or any of the excipients [metacresol, mannitol, succinic acid, NaOH/(HCl)]
  21. Likely to be non-compliant with respect to trial conduct
  22. Any other reason that in the opinion of the investigator would prevent the subject from completing participation or following the trial schedule

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): NCT04701203


Locations
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United States, California
Ascendis Pharma Investigational Site
San Jose, California, United States, 95148
United States, Illinois
Ascendis Pharma Investigational Site
Chicago, Illinois, United States, 60637
United States, Minnesota
Ascendis Pharma Investigational Site
Rochester, Minnesota, United States, 55905
United States, Nevada
Ascendis Pharma Investigational Site
Reno, Nevada, United States, 89511
United States, New York
Ascendis Pharma Investigational Site
New York, New York, United States, 10032
United States, North Carolina
Ascendis Pharma Investigational Site
Greenville, North Carolina, United States, 27834
United States, Pennsylvania
Ascendis Pharma Investigational Site
Kittanning, Pennsylvania, United States, 16201
Ascendis Pharma Investigational Site
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Ascendis Pharma Investigational Site
Austin, Texas, United States, 78731
Ascendis Pharma Investigational Site
Fort Worth, Texas, United States, 76132
United States, Washington
Ascendis Pharma Investigational Site
Spokane, Washington, United States, 99204
Canada, Nova Scotia
Ascendis Pharma Investigational Site
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
Ascendis Pharma Investigational Site
Oakville, Ontario, Canada, L6M 1M1
Canada, Quebec
Ascendis Pharma Investigational Site
Québec, Quebec, Canada, G1V 4G2
Denmark
Ascendis Pharma Investigational Site
København, Hovedstaden, Denmark, 2100
Ascendis Pharma Investigational Site
Aarhus, Midtjylland, Denmark, 8200
Ascendis Pharma Investigational Site
Køge, Sjælland, Denmark, 4600
Germany
Ascendis Pharma Investigational Site
Dresden, Sachsen, Germany, 01307
Hungary
Ascendis Pharma Investigational Site
Szeged, Csongrad, Hungary, 6720
Ascendis Pharma Investigational Site
Budapest, Hungary, 1083
Italy
Ascendis Pharma Investigational Site
Bologna, Emilia-Romagna, Italy, 40138
Ascendis Pharma Investigational Site
Roma, Lazio, Italy, 00128
Ascendis Pharma Investigational Site
Pisa, Piacenza, Italy, 56126
Norway
Ascendis Pharma Investigational Site
Oslo, Norway, 0176
Sponsors and Collaborators
Ascendis Pharma Bone Diseases A/S
Investigators
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Study Director: Aimee D Shu, MD Ascendis Pharma A/S North American Medical Monitor/Medical Expert
Study Director: Michael Beckert, MD Ascendis Pharma A/S European Medical Monitor/Medical Expert
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Responsible Party: Ascendis Pharma Bone Diseases A/S
ClinicalTrials.gov Identifier: NCT04701203    
Other Study ID Numbers: TCP-304
2020-003380-26 ( EudraCT Number )
First Posted: January 8, 2021    Key Record Dates
Last Update Posted: August 2, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ascendis Pharma A/S ( Ascendis Pharma Bone Diseases A/S ):
Hypoparathyroidism
Parathyroid Hormone
TransCon PTH
PTH(1-34)
Prodrug
Sustained Release
Parathyroid Hormone Replacement Therapy
Additional relevant MeSH terms:
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Hypoparathyroidism
Endocrine System Diseases
Parathyroid Diseases