PaTHway CHINA TRIAL: A Trial to Investigating the Safety, Tolerability and Efficacy of TransCon PTH in Adults With Hypoparathyroidism

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Brief Title

PaTHway CHINA TRIAL: A Trial to Investigating the Safety, Tolerability and Efficacy of TransCon PTH in Adults With Hypoparathyroidism

Official Title

PaTHway CHINA 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

Brief Summary

      This study is limited to conduct in China only. The primary objective is to assess the
      treatment effect of daily TransCon PTH on serum calcium (sCa) levels within the normal range
      and stopping from therapeutic doses of active vitamin D (calcitriol) or active vitamin D
      analogue (alfacalcidol) and calcium at 26 weeks of treatment. All subjects will start with 18
      mcg of study drug and will be individually and progressively titrated to an optimal dose over
      a 26-week double blind period, followed by an open label extension period up to 156 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.
    

Detailed Description

      Not Provided
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

The proportion of subjects who meet primary efficacy endpoint at 26 weeks of treatment

Secondary Outcome

 Change from baseline in HPES Symptom - Physical Domain score

Condition

Hypoparathyroidism

Intervention

TransCon PTH

Study Arms / Comparison Groups

 TransCon PTH
Description:  TransCon PTH at a starting dose of 18 mcg delivered once daily by subcutaneous injection

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

76

Start Date

July 28, 2021

Completion Date

December 2025

Primary Completion Date

December 2022

Eligibility 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 (below the ULN of local laboratory) serum PTH
             levels.

          3. Requirement for doses of SoC (e.g., calcitriol, alfacalcidol, calcium supplements) at
             or above a minimum threshold:

             • 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, and calcium should be stable for at least 5 weeks prior to Screening

          4. Optimization of supplements prior to randomization to achieve the target serum levels
             of:

               -  25(OH) vitamin D levels of 10-100 ng/mL (25-250 nmol/L) and

               -  Magnesium level in the normal range, or just below the normal range i.e.: ≥1.3
                  mg/dL (0.53 mmol/L) and

               -  Albumin-adjusted sCa level in the normal range, or just below the normal range,
                  i.e.: 7.8-10.6 mg/dL (or 1.95-2.64 mmol/L)

          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
             non-dominant 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/L

          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 SC 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 ICF 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
             non-melanoma skin cancer); active hyperparathyroidism; parathyroid carcinoma within 5
             years prior to Screening; acromegaly;or multiple endocrine neoplasia

          3. High risk thyroid cancer within 2 years, requiring suppression of TSH <0.2 mIU/L

          4. Long term 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. 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 mm Hg 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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Weibo Xia, MD, +86-21-52999605, [email protected]

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT05387070

Organization ID

TCP-306

Secondary IDs

CTR20212047

Responsible Party

Sponsor

Study Sponsor

Visen Pharmaceuticals (Shanghai) Co., Ltd.


Study Sponsor

Weibo Xia, MD, Principal Investigator, Department of endocrinology, Peking Union Medical College Hospital


Verification Date

May 2022