NCT04009291|CompletedPhase 2ResultsFDA Drug

A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH in Adults With Hypoparathyroidism

PaTH Forward

PaTH Forward: A Phase 2, 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

Ascendis Pharma A/S ClinicalTrials.gov

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1 other identifier

TransCon PTH TCP-201

Study Type

interventional

Target

Locations

6 countries

Sites

Timeline

RegisteredJul 2019

StartedAug 2019

CompletionApr 2025

Brief Summary

During the first four weeks of the trial, participants will be randomly assigned to one of four groups: three groups will receive fixed doses of TransCon PTH and one group will receive placebo. 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 four 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, Denmark, and Norway.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_2

Timeline

Completed

Started Aug 2019

Longer than P75 for phase_2

Geographic Reach

6 countries

15 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5.6 years study duration

First Submitted

Initial submission to the registry

June 20, 2019

Completed

15 days until next milestone

First Posted

Study publicly available on registry

July 5, 2019

Completed

2 months until next milestone

Study Start

First participant enrolled

August 27, 2019

Completed

6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 6, 2020

Completed

3.5 years until next milestone

Results Posted

Study results publicly available

September 1, 2023

Completed

1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 17, 2025

Completed

Last Updated

May 8, 2025

Status Verified

April 1, 2025

Enrollment Period

6 months

First QC Date

June 20, 2019

Results QC Date

March 1, 2023

Last Update Submit

April 23, 2025

Conditions

Hypoparathyroidism Endocrine System Diseases Parathyroid Diseases

Keywords

HypoparathyroidismParathyroid HormonePTH(1-34)ProdrugSustained ReleaseTransCon PTHParathyroid Hormone Replacement Therapy

Outcome Measures

Primary Outcomes (1)

Efficacy - Primary Endpoint During the Blinded Period
The percentage of subjects with albumin-adjusted serum calcium within the normal range, and spot morning fractional excretion of calcium (spot AM FECa) within normal range (≤2%) or a reduction by at least 50% from baseline, and not taking active vitamin D supplements, and taking ≤1000 mg/day of calcium supplements
Week 4

Secondary Outcomes (1)

Efficacy - Key Secondary Endpoint During the Blinded Period
Week 4

Study Arms (5)

TransCon PTH 15 mcg

EXPERIMENTAL

TransCon PTH 15 mcg delivered once daily by subcutaneous injection

Combination Product: TransCon PTH

TransCon PTH 18 mcg

EXPERIMENTAL

TransCon PTH 18 mcg delivered once daily by subcutaneous injection

Combination Product: TransCon PTH

TransCon PTH 21 mcg

EXPERIMENTAL

TransCon PTH 21 mcg delivered once daily by subcutaneous injection

Combination Product: TransCon PTH

Placebo

PLACEBO COMPARATOR

Placebo mimicking 15, 18, or 21 mcg of TransCon PTH delivered once daily by subcutaneous injection

Combination Product: Placebo for TransCon PTH

Open-Label Extension Period

EXPERIMENTAL

Subjects who complete the four-week blinded period are assigned to open-label treatment with TransCon PTH for up to 262 weeks, with up to an initial 14 weeks of TransCon PTH titration and standard of care optimization, followed by approximately 248 weeks of individualized dosing.

Combination Product: TransCon PTH

Interventions

TransCon PTHCOMBINATION_PRODUCT

TransCon PTH drug product is supplied as a clear solution containing TransCon PTH with a nominal PTH(1-34) content of 0.3 mg/mL in a pre-filled pen intended for subcutaneous injection.

Open-Label Extension PeriodTransCon PTH 15 mcgTransCon PTH 18 mcgTransCon PTH 21 mcg

Placebo for TransCon PTHCOMBINATION_PRODUCT

Placebo is supplied as a clear solution containing the formulation buffer for TransCon PTH in a pre-filled pen intended for subcutaneous injection.

Placebo

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Males and females aged ≥18 years.
Subjects with postsurgical chronic HP or auto-immune, genetic, or idiopathic HP for at least 26 weeks.
On a stable dose for at least 12 weeks (or 4 weeks if on Natpara as of September 2019) prior to Screening of:
≥0.25 μg BID of calcitriol (active vitamin D) or ≥0.5 μg BID or ≥1.0 μg daily of alfacalcidol (active vitamin D), and
≥400 mg BID calcium citrate or carbonate.
Optimization of supplements prior to randomization to achieve the target levels of:
(OH) vitamin D levels of 30-70 ng/mL (75-175 pmol/mL) and
Magnesium level within the normal range and
Albumin-adjusted or ionized serum calcium (sCa) level in the lower half of the normal range.
BMI 17-40 kg/m2 at Visit 1.
If ≤25 years of age, radiological evidence of epiphyseal closure based on x-ray of non-dominant wrist and hand.
eGFR \>30 mL/min/1.73m2 during Screening.
Thyroid-stimulating hormone (TSH) within normal laboratory limits within the 12 weeks prior to Visit 1; if on suppressive therapy for thyroid cancer, TSH level must be ≥0.2 μIU/mL.
If treated with thyroid hormone replacement therapy, the dose must be stable for at least 12 weeks prior to Visit 1.
Able to perform daily subcutaneous self-injections of study drug (or have a designee perform injection) via a pre-filled injection pen.
+1 more criteria

You may not qualify if:

Known activating mutation in the calcium-sensing receptor (CaSR) gene.
Impaired responsiveness to PTH (pseudohypoparathyroidism) which is characterized as PTH-resistance, with elevated PTH Levels in the setting of hypocalcemia.
Any disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than HP, such as active hyperthyroidism; Paget's disease; hypomagnesemia; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus; severe and chronic cardiac, liver, or renal disease; Cushing syndrome; rheumatoid arthritis; multiple myeloma; active pancreatitis; malnutrition; rickets; recent prolonged immobility; active malignancy (other than low-risk well differentiated thyroid cancer or basal cell skin cancer); parathyroid carcinoma within 5 years prior to Screening; acromegaly; multiple endocrine neoplasia types 1 and 2.
Use of loop diuretics, phosphate binders (other than calcium carbonate/calcium citrate), digoxin, lithium, methotrexate, or systemic corticosteroids (other than replacement therapy).
Use of thiazide diuretic within 4 weeks prior to the Screening 24-hour urine collection or the first dose adjustment of SOC during Screening.
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 5 weeks prior to Visit 1.
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 Visit 1.
Use of bisphosphonates (oral or IV) or denosumab within 2 years prior to Visit 1.
Non-hypocalcemic seizure disorder with a history of a seizure within 26 weeks prior to Visit 1.
Increased risk for osteosarcoma, such as those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, open epiphyses, hereditary disorders predisposing to osteosarcoma, or with a prior history of substantial external beam or implant radiation therapy involving the skeleton.
Pregnant or lactating women. Note: Highly effective contraception (see Appendix 7) is required for sexually active women of childbearing potential during the trial and for 2 weeks after the last dose of study drug, and pregnancy testing will be performed throughout the trial. Sexually active women of childbearing potential who are unwilling to use highly effective contraception are excluded from the trial.
Diagnosis of drug or alcohol dependence within 3 years prior to Visit 1.
Disease processes that may adversely affect gastrointestinal absorption including but not limited to short bowel syndrome, bowel resection, gastric bypass, tropical sprue, active celiac disease, active ulcerative colitis, gastroparesis, AIRE gene mutations with malabsorption, and active Crohn's disease.
Chronic or severe cardiac disease within 26 weeks prior to Visit 1 including but not limited to congestive heart failure, myocardial infarction, QTcF \>430 msec (males) or \>450 msec (females), severe or uncontrolled arrhythmias, bradycardia (resting heart rate \<50 beats/minute), symptomatic hypotension, systolic BP \<80 mm Hg or diastolic \<40 mm Hg, or poorly controlled hypertension (systolic BP \>150 mm Hg or diastolic \>95 mm Hg).
Cerebrovascular accident within 5 years prior to Visit 1.
+5 more criteria

Contact the study team to confirm eligibility.