Actively Recruiting
Safety and Efficacy of PTH-IA
Led by National Institute of Dental and Craniofacial Research (NIDCR) · Updated on 2026-04-29
12
Participants Needed
1
Research Sites
156 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Safety and Efficacy of PTH-IA
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Willingness of participant and/or guardian to sign informed consent before study procedures
- Adults aged 18 years or older for Period 1
- Adults and children aged 3 to 17 years for Period 2
- Minimum body weight of 35 kg for Period 1 and 18 kg for Period 2
- Confirmed activating germline mutation of PTH1R (H223R, I458K, I458R, T410P, or T410R)
- Female participants of reproductive potential must agree to use one form of highly effective contraception
- Males of reproductive potential must use condoms or other effective contraception methods
- Willingness and ability to comply with all study procedures and availability for the study duration including travel to NIH Clinical Center
You will not qualify if you...
- Pregnancy or lactation
- 25-hydroxyvitamin D level 20 ng/mL or lower (with rescreening allowed after up to 6 months of repletion)
- Clinically significant renal disease with eGFR 45 mL/min/1.73 m2 or less
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels more than twice the upper limit of normal (with rescreening allowed after up to 6 months)
- Hemoglobin below 12 gm/dL for females and girls 16 years and older, below 13 gm/dL for males and boys 16 years and older, or below 11.5 gm/dL in children 15 years and younger (with rescreening allowed after up to 6 months if due to nutrient deficiency)
- Hypersensitivity or intolerance to any component of PTH-IA
- History of surgical removal of all parathyroid glands
- Treatment with bisphosphonates within 6 months before screening
- Treatment with denosumab within 3 months before screening
- Treatment with thiazides within 4 weeks before screening
- Any other significant medical conditions that could affect safety or data interpretation according to the study team
AI-Screening
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Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
O
Olivia J de Jong, C.R.N.P.
CONTACT
A
Alison M Boyce, M.D.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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