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Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

Short name PaTH Forward

Overview

Status
Completed
Phase
Phase 2
Enrollment
59 participants (actual)
Sponsor
Ascendis Pharma A/S · Industry
Design
Randomized · Quadruple masking
Countries
6 countries

United States, Canada, Denmark, Germany, Italy, Norway

Start
27 Aug 2019
Primary completion
6 Mar 2020
Completion
17 Apr 2025
First posted
5 Jul 2019
Last update posted
18 Jun 2026
Conditions
Hypoparathyroidism · Endocrine System Diseases · Parathyroid Diseases

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2020202220242026
  1. Ph 2

    PaTH Forward

    NCT04009291

    27 Aug 2019 to 17 Apr 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

During the first four weeks of the trial, participants were randomly assigned to one of four groups: three groups received fixed doses of TransCon PTH and one group received placebo. TransCon PTH or placebo were administered as a subcutaneous injection using a pre-filled injection pen. Neither trial participants nor their doctors know who has been assigned to each group. After the four weeks, participants continued in the trial as part of a long-term extension period. During the extension, all participants received TransCon PTH, with the dose adjusted to their individual needs. This was a global trial that was conducted in the United States, Canada, Germany, Denmark, Italy and Norway.

Interventions

  • TransCon PTHCombination product
  • Placebo for TransCon PTHCombination product

Arms5

  • Experimental

    Double Blind: TransCon PTH 15 mcg

    TransCon PTH 15 mcg delivered once daily by subcutaneous injection

  • Experimental

    Double Blind: TransCon PTH 18 mcg

    TransCon PTH 18 mcg delivered once daily by subcutaneous injection

  • Experimental

    Double Blind: TransCon PTH 21 mcg

    TransCon PTH 21 mcg delivered once daily by subcutaneous injection

  • Placebo comparator

    Placebo

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

  • Experimental

    Open-Label Extension Period: TransCon PTH

    Participants who completed the 4-week double-blind period, continued into the open-label extension period and received treatment with TransCon PTH up to Week 266, with up to an initial 14 weeks of TransCon PTH titration and standard of care optimization, followed by approximately 248 weeks of individualized doses of TransCon PTH (allowable dose range: 6 to 60 mcg/day).

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Efficacy - Primary Endpoint During the Blinded Period

    Time frame · Week 4

    Registry description

    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

Secondary outcomes(1)
  1. Efficacy - Key Secondary Endpoint During the Blinded Period

    Time frame · Week 4

    Registry description

    The percentage of subjects with albumin-adjusted serum calcium within the normal range, and spot AM FECa within the normal range (≤2%) or a reduction by at least 50% from baseline, and not taking active vitamin D supplements, and taking ≤ 500 mg/day of calcium supplements

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· Week 4

Efficacy - Primary Endpoint During the Blinded Period

GroupValue (Percentage of participants)
TransCon PTH 15 mcg50.0
TransCon PTH 18 mcg40.0
TransCon PTH 21 mcg60.0
Placebo26.7
Secondary and other outcome results(1)
Secondary outcomeNumber· Week 4

Efficacy - Key Secondary Endpoint During the Blinded Period

GroupValue (Percentage of participants)
TransCon PTH 15 mcg50.0
TransCon PTH 18 mcg26.7
TransCon PTH 21 mcg60.0
Placebo20.0

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Double Blind: TransCon PTH 15 mcgTransCon PTH 15 mcg delivered once daily by subcutaneous injection TransCon PTH: 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.0 / 140 / 146 / 14
Double Blind: TransCon PTH 18 mcgTransCon PTH 18 mcg delivered once daily by subcutaneous injection TransCon PTH: 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.0 / 150 / 155 / 15
Double Blind: TransCon PTH 21 mcgTransCon PTH 21 mcg delivered once daily by subcutaneous injection TransCon PTH: 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.0 / 150 / 157 / 15
Double Blind: PlaceboPlacebo mimicking 15, 18, or 21 mcg of TransCon PTH delivered once daily by subcutaneous injection Placebo for TransCon PTH: Placebo is supplied as a clear solution containing the formulation buffer for TransCon PTH in a pre-filled pen intended for subcutaneous injection.0 / 150 / 156 / 15
Total TransCon PTH PeriodParticipants who completed the 4-week double blind treatment period in placebo and TransCon PTH groups, continued into the open-label extension period and received treatment with TransCon PTH up to Week 266. This period refers to total period of exposure to TransCon PTH. For participants randomized to TransCon PTH at enrollment, the "TransCon PTH Period" was the time from first dose of blinded TransCon PTH until final analysis in OLE period. The TransCon PTH Period for participants randomized to placebo at enrollment was the time from first exposure to TransCon PTH at the time of cross-over from placebo, until final analysis in the OLE period.0 / 598 / 5957 / 59

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies4

Studies that cite this trial.

Studies with results

3 studies on this page

Indexing hint: Randomized controlled trial · 2026

12 results

Palopegteriparatide for adults with chronic hypoparathyroidism: skeletal dynamics through 3 years of the phase 2 PaTH forward trial.

Rubin et al. 2026Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Researchcited by 7

PMID 41636590PMC13616104DOI 10.1093/jbmr/zjag013PUB-41636590

CC BY12 results

Indexing hint: Randomized controlled trial · 2023

7 results

Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial.

Khan et al. 2023Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Researchcited by 81

PMID 36271471PMC10099823DOI 10.1002/jbmr.4726PUB-36271471

CC BY7 results

Indexing hint: Randomized controlled trial · 2022

10 results

PaTH Forward: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of TransCon PTH in Adult Hypoparathyroidism.

Khan et al. 2022The Journal of clinical endocrinology and metabolismcited by 48

PMID 34347093PMC8684498DOI 10.1210/clinem/dgab577PUB-34347093

Free to read · publisher termsCC BY-NC-ND10 results

More studies

1 study on this page

Indexing hint: Randomized controlled trial · 2026

Corrected

Patient-reported outcomes in palopegteriparatide-treated adults with hypoparathyroidism: PaTH Forward trial extension.

Rubin et al. 2026The Journal of clinical endocrinology and metabolismcited by 2

PMID 41365829PMC13017087DOI 10.1210/clinem/dgaf653PUB-41365829

CC BY

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. Males and females aged ≥18 years. 2. Subjects with postsurgical chronic HP or auto-immune, genetic, or idiopathic HP for at least 26 weeks. 3. 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. 4. Optimization of supplements prior to randomization to achieve the target levels of: * 25(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. 5. BMI 17-40 kg/m2 at Visit 1. 6. If ≤25 years of age, radiological evidence of epiphyseal closure based on x-ray of non-dominant wrist and hand. 7. eGFR \>30 mL/min/1.73m2 during Screening. 8. 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. 9. If treated with thyroid hormone replacement therapy, the dose must be stable for at least 12 weeks prior to Visit 1. 10. Able to perform daily subcutaneous self-injections of study drug (or have a designee perform injection) via a pre-filled injection pen. 11. Written, signed, informed consent of the subject. Exclusion Criteria: 1. Known activating mutation in the calcium-sensing receptor (CaSR) gene. 2. Impaired responsiveness to PTH (pseudohypoparathyroidism) which is characterized as PTH-resistance, with elevated PTH Levels in the setting of hypocalcemia. 3. 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. 4. Use of loop diuretics, phosphate binders (other than calcium carbonate/calcium citrate), digoxin, lithium, methotrexate, or systemic corticosteroids (other than replacement therapy). 5. Use of thiazide diuretic within 4 weeks prior to the Screening 24-hour urine collection or the first dose adjustment of SOC during Screening. 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 5 weeks prior to Visit 1. 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 Visit 1. 8. Use of bisphosphonates (oral or IV) or denosumab within 2 years prior to Visit 1. 9. Non-hypocalcemic seizure disorder with a history of a seizure within 26 weeks prior to Visit 1. 10. 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. 11. 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. 12. Diagnosis of drug or alcohol dependence within 3 years prior to Visit 1. 13. 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. 14. 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). 15. Cerebrovascular accident within 5 years prior to Visit 1. 16. History of renal colic or acute gout within 52 weeks prior to Visit 1. 17. Any disease or condition that, in the opinion of the investigator, may 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 1-year duration of the trial. 18. Known allergy or sensitivity to PTH or any of the excipients. 19. Participation in another clinical trial in which receipt of investigational drug or device occurred within 8 weeks (or at least 5.5 times the half-life of the investigational drug) prior to Visit 1. 20. Likely to be non-compliant with respect to trial conduct.

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