Safety and Efficacy of PTH-IA

Recruiting now · Phase 1/Phase 2

Conditions studied: Jansen's Metaphyseal Chondrodysplasia

In brief

Jansen s Metaphyseal Chondrodysplasia (JMC) is a very rare disorder with only approximately 30 people known to have the disease worldwide. It is caused by parathyroid hormone 1 receptor (PTH1R) variants leading to constitutive activation of the receptor for parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP). PTH1R is predominantly expressed in the kidneys and bone and growth-plate chondrocytes. Individuals with JMC develop severe growth impairment resulting in significant short stature, scoliosis, frequent fractures, bone pain, mineral-ion abnormalities (typically hypercalcemia and hypercalciuria), hypertension, and chronic kidney disease due to nephrocalcinosis and nephrolithiasis. Children often undergo multiple surgeries for skeletal fractures and deformities; mobility is commonly impaired, usually requiring assistive devices for ambulation. Other complications may include premature closure of cranial sutures and cranial nerve compressions with the potential for vision and/or hearing loss \[1-3\]. Physical function impairment and the need for complication-related operations have profound deleterious effects on quality of life in individuals with JMC. There are currently no approved therapies for JMC, and novel therapies are critically needed to prevent irreversible disease complications and improve patient quality of life. The inventors of the drug, parathyroid hormone inverse agonist (PTH-IA), have considerable expertise in both the basic and clinical aspects of PTH/PTHrP receptor molecular biology and pharmacology. They reported the first PTH1R JMC mutations (including the H223R mutation) over 20 years ago and identified certain PTH antagonist ligands that function as inverse agonists on the PTH1R JMC mutant receptors \[2, 4\]. These ligands suppress the mutant receptor s elevated basal rates of cAMP signalling, as assessed in cultured cells and animal models. In vivo studies confirm that inverse agonist ligands may be effective in treating JMC. This study involves the use of PTH-IA, a 30-amino acid PTH inverse agonist ligand with the amino acid sequence \[Leu11,dTrp12,Trp23,Tyr36\]-PTHrP(7-36)NH2. We hypothesize that PTH-IA will be a safe and effective treatment for individuals with JMC.

Key facts

Study ID: NCT07541209
Run by: National Institute of Dental and Craniofacial Research (NIDCR)
People needed: 12
Starts: 2026-05-27
Expected to finish: 2029-06-01
Last updated by the study team: 2026-08-06

Who can join

Age: 3 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

An individual who meets any of the following criteria will be excluded from participation in this study:
Pregnancy or lactation
25-hydroxyvitamin D <=20 ng/mL. Patients will be eligible for rescreening after a repletion period lasting up to 6 months.
Clinically significant renal disease with estimated glomerular filtration rate (eGFR) <=45 mL/ min/1.73 m2.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times the upper limit of normal. If transaminitis is present, patients will be eligible for rescreening for a period of up to 6 months.
Hgb <12 gm/dL for women and girls >=16 years, <=13 gm/dL for men and boys >=16 years, and <=11.5 gm/dL in children <=15 years. If reduced hemoglobin levels are related to iron, B12, or folate deficiency, patients will be eligible for rescreening after a repletion period lasting up to 6 months.
Hypersensitivity or intolerance to any active substance or excipient of PTH-IA
History of surgical removal of all parathyroid glands.
Treatment with bisphosphonate use within 6 months of screening
Treatment with denosumab within 3 months of screening
Treatment with thiazides within 4 weeks of screening
Any other significant medical conditions that, in the opinion of the study team, may present a concern for participant safety or difficulty with data interpretation.

Where it is running

National Institutes of Health Clinical Center — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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