TransCon PTH for Hypoparathyroidism

(PaTH Forward Trial)

No longer recruiting at 15 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ascendis Pharma A/S

Must be taking: Active vitamin D, Calcium

Must not be taking: Loop diuretics, Corticosteroids, Bisphosphonates, others

Disqualifiers: Diabetes, Cardiac disease, Malignancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TransCon PTH for individuals with hypoparathyroidism, a condition where insufficient parathyroid hormone affects calcium levels. Initially, the trial compares different doses of TransCon PTH with a placebo (a treatment with no active drug) to evaluate its effectiveness. After four weeks, all participants will switch to TransCon PTH for a longer period to determine the best dose for each individual. This study suits those who have had hypoparathyroidism for at least six months and currently manage it with medications like active vitamin D and calcium supplements. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but certain medications are not allowed, such as loop diuretics, phosphate binders, and some others. It's best to discuss your current medications with the trial team to see if they are permitted.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that TransCon PTH is generally safe and well-tolerated for people with hypoparathyroidism. In earlier studies, participants used TransCon PTH for up to three years without any new safety issues. Most side effects were mild to moderate. These results suggest that the treatment has maintained a good safety record so far. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for hypoparathyroidism?

TransCon PTH is unique because it offers a potentially more effective and convenient treatment for hypoparathyroidism. Unlike current options, which often involve daily high doses of calcium and vitamin D supplements, TransCon PTH is a once-daily subcutaneous injection that directly delivers parathyroid hormone (PTH), aiming to restore natural calcium balance in the body. Researchers are excited about its ability to provide a more physiologic replacement of PTH, potentially reducing the burden of standard treatments and improving quality of life for patients.

What evidence suggests that TransCon PTH might be an effective treatment for hypoparathyroidism?

Research has shown that TransCon PTH, administered in doses of 15, 18, or 21 mcg, effectively treats hypoparathyroidism. One study found that after a year, patients experienced lasting improvements in symptoms and overall health. Another study demonstrated that TransCon PTH improved health outcomes and reduced disease-related symptoms. Real-world data supports its effectiveness, showing positive effects on patients' health. Additionally, a three-year trial confirmed ongoing improvements in symptoms and quality of life for patients with hypoparathyroidism. ^{1 3 4 5 6}

Who Is on the Research Team?

Aimee Shu, MD

Principal Investigator

Ascendis Pharma A/S Medical Monitor/Medical Expert

Are You a Good Fit for This Trial?

Adults over 18 with chronic hypoparathyroidism (HP) for at least half a year, taking specific vitamin D and calcium supplements, can join this trial. They must be able to self-inject medication and not have certain genetic mutations or recent use of related drugs. Pregnant women, those with severe heart or kidney issues, drug/alcohol dependence, or other conditions affecting calcium metabolism are excluded.

Inclusion Criteria

My kidney function is good.

Your body mass index (BMI) is between 17 and 40, which is a measure of your weight in relation to your height.

25(OH) vitamin D levels of 30-70 ng/mL (75-175 pmol/mL) and

Exclusion Criteria

I haven't taken drugs affecting bone metabolism like calcitonin or fluoride in the last 12 weeks.

My genetic test shows a mutation in the CaSR gene.

I don't have any health issues that could stop me from finishing the trial or that would make the trial unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to receive either TransCon PTH or placebo for four weeks, administered as a subcutaneous injection using a pre-filled injection pen

4 weeks

Open-label extension

Participants receive open-label TransCon PTH with dose adjustments based on individual needs for up to 262 weeks

262 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo for TransCon PTH
• TransCon PTH

Trial Overview The trial is testing TransCon PTH against a placebo in adults with HP. Initially, participants are randomly assigned to receive either the drug or placebo via injection without knowing which one they're getting. After four weeks, all move on to receive TransCon PTH tailored to their needs in an extension study.

How Is the Trial Designed?

Group I: TransCon PTH 21 mcg Experimental Treatment 1 Intervention

TransCon PTH 21 mcg delivered once daily by subcutaneous injection

Group II: TransCon PTH 18 mcg Experimental Treatment 1 Intervention

TransCon PTH 18 mcg delivered once daily by subcutaneous injection

Group III: TransCon PTH 15 mcg Experimental Treatment 1 Intervention

TransCon PTH 15 mcg delivered once daily by subcutaneous injection

Group IV: Open-Label Extension Period Experimental Treatment 1 Intervention

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.

Group V: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Ascendis Pharma A/S

Lead Sponsor

Trials

15

Recruited

1,600+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39376010/

52-Week Results From the Phase 3 PaTHway Trial Conclusion: At week 52 of the PaTHway trial, TransCon PTH showed sustained efficacy, safety, and tolerability in adults with hypoparathyroidism.

2. academic.oup.com academic.oup.com/jcem/article/110/4/951/7815470

Efficacy and Safety of TransCon PTH in Adults With ... TransCon PTH treatment was associated with sustained improvements in clinical outcomes as well as disease-related symptoms and the impact of hypoparathyroidism ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1530891X25010031

Early U.S. Real-World Treatment Patterns and Outcomes in ... Objective. To examine the impact of palopegteriparatide (YORVIPATH; TransCon PTH) on real-world clinical outcomes in adult patients with ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40846304/

Early U.S. Real-World Treatment Patterns and Outcomes in ... Objective: To examine the impact of palopegteriparatide (YORVIPATH; TransCon PTH) on real-world clinical outcomes in adult patients with ...

5. investors.ascendispharma.com investors.ascendispharma.com/news-releases/news-release-details/new-3-year-phase-3-data-confirmed-sustained-response-transconr

New 3-Year Phase 3 Data Confirmed Sustained Response ... Patients in the trial reported continued improvements from baseline in their hypoparathyroidism-related symptoms and health-related quality of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04701203

NCT04701203 | A Trial Investigating the Safety, Tolerability ... A Trial Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Daily in Adults With Hypoparathyroidism (PaTHway). ClinicalTrials ...