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HypoparathyroidismPhase 2PaTH ForwardNCT04009291

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

A Phase 2 study testing TransCon PTH in people with Hypoparathyroidism and Endocrine System Diseases, run by Ascendis Pharma A/S at 15 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TransCon PTH
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
59 participants
Where
15 sitesin 6 countries
Study dates
27 Aug 2019to 17 Apr 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • 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.
  • Written, signed, informed consent of the subject.

Who cannot join

  • 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.
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  • 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.
  • History of renal colic or acute gout within 52 weeks prior to Visit 1.
  • 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.
  • Known allergy or sensitivity to PTH or any of the excipients.
  • 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.
  • Likely to be non-compliant with respect to trial conduct.

Trial locations and contacts

15 sites in 6 countries.

15 sites in 6 countries

United States5 sites
  • Ascendis Pharma Investigational Site

    Chicago, Illinois, 60637

  • Ascendis Pharma Investigational Site

    Great Neck, New York, 11021

  • Ascendis Pharma Investigational Site

    New York, New York, 10032

  • Ascendis Pharma Investigational Site

    Philadelphia, Pennsylvania, 19104

  • Ascendis Pharma Investigational Site

    Rochester, Minnesota, 55901

Other trials in United States

Italy4 sites
  • Ascendis Pharma Investigational Site

    Bologna, 40138

  • Ascendis Pharma Investigational Site

    Milan, 20132

  • Ascendis Pharma Investigational Site

    Pisa, 56124

  • Ascendis Pharma Investigational Site

    Rome, 00128

Other trials in Italy

Denmark3 sites
  • Ascendis Pharma Investigational Site

    Aalborg, 9000

  • Ascendis Pharma Investigational Site

    Aarhus, 8200

  • Ascendis Pharma Investigational Site

    Copenhagen, 2200

Other trials in Denmark

Canada1 site
  • Ascendis Pharma Investigational Site

    Oakville, Ontario, L6M 1M1

Other trials in Canada

Germany1 site
  • Ascendis Pharma Investigational Site

    Dresden, 01307

Other trials in Germany

Norway1 site
  • Ascendis Pharma Investigational Site

    Oslo, 0176

Other trials in Norway

About this study

Official title: 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

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.

Being tested
TransCon PTH, Placebo for TransCon PTH
Keywords
Hypoparathyroidism, Parathyroid Hormone, PTH(1-34), Prodrug, Sustained Release, TransCon PTH, Parathyroid Hormone Replacement Therapy
Medical subject headings
Hypoparathyroidism, Endocrine System Diseases, Parathyroid Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • 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.

Study groups in NCT04009291
Study groupRoleWhat they receive
Double Blind: TransCon PTH 15 mcgExperimentalTransCon PTH 15 mcg delivered once daily by subcutaneous injection
Receives: Combination Product: TransCon PTH
Double Blind: TransCon PTH 18 mcgExperimentalTransCon PTH 18 mcg delivered once daily by subcutaneous injection
Receives: Combination Product: TransCon PTH
Double Blind: TransCon PTH 21 mcgExperimentalTransCon PTH 21 mcg delivered once daily by subcutaneous injection
Receives: Combination Product: TransCon PTH
PlaceboPlacebo comparatorPlacebo mimicking 15, 18, or 21 mcg of TransCon PTH delivered once daily by subcutaneous injection
Receives: Combination Product: Placebo for TransCon PTH
Open-Label Extension Period: TransCon PTHExperimentalParticipants 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).
Receives: Combination Product: TransCon PTH

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Week 4

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

    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

    Measured: Week 4

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jul 2019
  2. Study start27 Aug 2019
  3. Primary completion6 Mar 2020
  4. Study completion17 Apr 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Double-blind, placebo controlled, parallel group with subjects randomized into 4 treatment groups (1:1:1:1): TransCon PTH 15 mcg/day, TransCon PTH 18 mcg/day, TransCon PTH 21 mcg/day, placebo
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04009291
Sponsor's protocol ID
TransCon PTH TCP-201
Acronym
PaTH Forward
Status last verified
May 2026
First submitted
20 Jun 2019
Last updated
18 Jun 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Publications

  • Rubin MR, Clarke BL, Hofbauer LC, Khan A, Schwarz P, Vokes T, Ahmed I, Palermo A, Cetani F, Pagotto U, Zhao C, Ominsky MS, Lai B, Ukena J, Shu AD, Rejnmark L. Palopegteriparatide for Adults with Chronic Hypoparathyroidism: Skeletal Dynamics Through 3 yr of the Phase 2 paTH Forward Trial. J Bone Miner Res. 2026 Feb 4:zjag013. doi: 10.1093/jbmr/zjag013. Online ahead of print.

    PubMed 41636590
  • Rubin M, Palermo A, Vokes T, Khan AA, Schwarz P, Cetani F, Pagotto U, Tsourdi E, Sikjaer T, Pfeiffer KM, Brod M, McLeod LD, Zhao C, Noori W, Shu AD, Smith AR. Patient-reported outcomes in palopegteriparatide-treated adults with hypoparathyroidism: PaTH Forward trial extension. J Clin Endocrinol Metab. 2026 Mar 17;111(4):945-952. doi: 10.1210/clinem/dgaf653.

    PubMed 41365829
  • Khan AA, Rejnmark L, Rubin M, Schwarz P, Vokes T, Clarke B, Ahmed I, Hofbauer L, Marcocci C, Pagotto U, Palermo A, Eriksen E, Brod M, Markova D, Smith A, Pihl S, Mourya S, Karpf DB, Shu AD. PaTH Forward: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of TransCon PTH in Adult Hypoparathyroidism. J Clin Endocrinol Metab. 2022 Jan 1;107(1):e372-e385. doi: 10.1210/clinem/dgab577.

    PubMed 34347093
  • Khan AA, Rubin MR, Schwarz P, Vokes T, Shoback DM, Gagnon C, Palermo A, Marcocci C, Clarke BL, Abbott LG, Hofbauer LC, Kohlmeier L, Pihl S, An X, Eng WF, Smith AR, Ukena J, Sibley CT, Shu AD, Rejnmark L. Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial. J Bone Miner Res. 2023 Jan;38(1):14-25. doi: 10.1002/jbmr.4726. Epub 2022 Nov 12.

    PubMed 36271471

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TransCon PTH in people with Hypoparathyroidism and Endocrine System Diseases, run by Ascendis Pharma A/S at 15 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Italy, Denmark, Canada, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy - Primary Endpoint During the Blinded Period (time frame: Week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04009291, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2026.

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