Jansen's Metaphyseal ChondrodysplasiaPhase 1/2NCT07541209
Safety and Efficacy of PTH-IA
A Phase 1/2 study testing PTH-IA in people with Jansen's Metaphyseal Chondrodysplasia, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 3 to 100 years
- Conditions the study is for
- Jansen's Metaphyseal Chondrodysplasia
- What is being tested?
- PTH-IA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 27 May 2026to 1 Jun 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 3 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Willingness of participant and/or guardian to sign a written informed consent form, which must be obtained prior to initiation of study procedures.
- Period 1: Adults >=18 years of age
- Period 2: Adults and children 3-17 years of age
- Minimum body weight of 35 kg for participation in Period 1 and 18 kg for participation in Period 2.
- Have an activating germline mutation of PTHIR (H223R, I458K, I458R, T410P, or T410R)
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- Female participants of reproductive potential must agree to use one form of highly effective contraception. Highly effective contraception includes:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post- ovulation methods) and withdrawal are not acceptable methods of contraception.
- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment.
- Male sterilization (at least 6 months prior to screening). For female participants in the study, the vasectomized male partner should be the sole partner for that participant for the study duration.
- Use of oral, injected, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormonal vaginal ring or transdermal hormone contraception
- Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception used correctly by the male partner: condom or occlusive cap (diaphragm or cervical/ vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
- For males of reproductive potential: use of condoms or other methods described above to ensure effective contraception with partner.
- Stated willingness to comply with all study procedures and availability for the duration of the study, including the ability and willingness to travel to the NIH Clinical Center.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: A Phase 1/2 Open-label First-in-Human Dose-Escalating Safety and Efficacy Study Evaluating Subcutaneous Administration of PTH-IA in Adults and Children With Jansen s Metaphyseal Chondrodysplasia (JMC)
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.
Read the detailed description
Study Description:
This is a Phase 1/2 open-label, single-arm study to evaluate the safety of multiple ascending doses of PTH-IA administered subcutaneously twice a day in individuals with JMC conducted at the National Institutes of Health Clinical Center.
Objectives Primary Objectives
Period 1 - Adult
- Evaluate the safety and tolerability of PTH-IA in adults with JMC (>=18 years)
- Evaluate the pharmacokinetics (PK) of multiple ascending doses of PTH-IA in adults (>= 18 y/o) years old with JMC
Period 2 - Adult and Pediatrics
- Evaluate the safety and tolerability of PTH-IA in adults and children aged 3-17 years old with JMC
- Evaluate the pharmacokinetics (PK) of multiple ascending doses of PTH-IA in children aged 3-17 years old with JMC
- Evaluate the effect of PTH-IA on serum PTH levels on children and adults with JMC
Secondary Objectives
Periods 1 and 2
- Identify the optimal dose range of PTH-IA
- Evaluate potential measures of efficacy of PTH-IA in JMC
Exploratory Objectives
Periods 1 and 2
- Evaluate the effect of PTH-IA on physical function
- Evaluate the effect of PTH-IA on pain and health-related quality of life (QOL)
- Evaluate the immunogenicity of PTH-IA
- Describe the baseline and response to treatment histological characteristics of bone lesions in JMC
Endpoints Primary Endpoints
Period 1
- Dose limiting toxicities (DLTs) and incidence, severity, seriousness, and causality of all treatment-emergent adverse events (TEAEs)
- PK parameters after multiple ascending doses of PTH-IA
Period 2
- Dose limiting toxicities (DLTs) and incidence, severity, seriousness, and causality of all treatment-emergent adverse events (TEAEs)
- PK parameters after multiple ascending doses of PTH-IA
- Change in serum PTH from baseline to end of treatment
Secondary Endpoints
Periods 1 and 2
- Absolute levels and percentage change from baseline in serum corrected calcium pre- and post-intervention at end of treatment
- Absolute levels and change in ratio of serum corrected calcium to PTH ([mg/dl]/[pg/ml]) pre- and post-intervention at end of study
- Absolute levels and percentage change from baseline in fractional excretion of calcium at end of treatment
- Change in tubular reabsorption of phosphate and ratio of tubular maximum reabsorption of phosphate to GFR between pre- and post-intervention at end of treatment
- Absolute levels and percentage change from baseline in urine nephrogenous cAMP at end of treatment
- Absolute levels and percentage change from baseline in serum phosphate at end of treatment
- Change in bone turnover markers (P1NP, BSALP, CTX, osteocalcin) between pre- and post-intervention at end of treatment
- Absolute levels and percentage change from baseline in markers of mineral homeostasis: 1,25(OH)2 vitamin D and ratio of 1,25(OH)2 vitamin D to PTH at end of treatment
- Change in pre-defined sentinel skeletal lesion metabolic activity representing region of most intense pathology as measured by 18F- NaF PET/CT (<= 5 lesions) between pre- and post-intervention at end of treatment
- Change in pre-defined target skeletal lesion mineral density representing region of most intense pathology as measured by 18F- NaF PET/CT (<= 5 lesions) between pre- and postintervention at end of treatment
- Change in nephrocalcinosis scores on ultrasound from baseline to end of treatment (0-no nephrocalcinosis and 3- severe nephrocalcinosis)
- Change in HR-pQCT parameters of the radius and tibia: total BMD, cortical and trabecular BMD; cortical thickness, cortical porosity, BV/TV, trabecular number, thickness, and separation; stiffness and failure load of the peripheral skeleton
- Minimally effective dose defined by dose at which the mean of two highest PTH levels increases to 30-40 pg/mL (in individuals with baseline PTH <= 20 pg/mL) in the absence of DLTs. In individuals with baseline PTH >20 pg/mL, the optimal dose will be the dose at which the mean of two highest PTH obtained increases to 55-65 pg/mL in the absence ofDLTs.
Exploratory Endpoints
Periods 1 and 2
- Change from baseline in range of motion of upper and lower extremities
- Change from baseline in manual muscle strength testing of bilateral upper and lower extremities
- Change from baseline in gait assessment
- Change from baseline in assessment of skeletal bowing
- Change from baseline in walking speed
- Change from baseline in PROMIS pain intensity, pain interference, mobility, and fatigue scores
- Development and characterization of anti-drug antibodies (ADAs)
- JMC lesion histology as assessed by bone biopsies
- Conditions
- Jansen's Metaphyseal Chondrodysplasia
- Being tested
- PTH-IA
- Keywords
- Jansen Type Metaphyseal Chondrodysplasia, Parathyroid Hormone 1 Receptor (PTH1R), PTH1R Mutations, Parathyroid Hormone-Related Peptide (PTHrP), Parathyroid Hormone Inverse Agonist (PTH-IA)
- Medical subject headings
- Jansen type metaphyseal chondrodysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTH-IADrug
PTH-IA is a 30-amino acid peptide expected to act as an inverse agonist, decreasing the proportion of mutant PTH1R receptors in the active-state conformation and leading to a reduction in basal cAMP signaling. This hypothesis is based on results from PTH-IA treatment of cells and animal models expressing the different PTH1R mutations seen in JMC individuals. In-vitro studies of HEK293 cells stably transfected with a Glosensor cAMP reporter and plasmids expressing the different PTH1R constitutively active mutant JMC alleles (H223R, I458K, I458R, T410P, and T410R) showed that the cells displayed agonist-independent cAMP generation. Treatment of cells expressing the different PTH1R mutations with PTH-IA resulted in a rapid and persistent reduction in basal cAMP signaling, indicating that the peptide can act as an inverse agonist and thus decreases the proportion of mutant receptors in the active-state conformation.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with PTH-IA | Experimental | All participants will receive PTH-IA for up to 90+/-7 days in Period 1, and 24 weeks +/- 7 days in Period 2. Receives: Drug: PTH-IA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Period 1 - Adult: Evaluate the safety and tolerability of PTH-IA in adults with JMC (>= 18 years)
To assess dose-limiting toxicities (DLTs) and incidence, severity, seriousness, and causality of all treatment-emergent adverse events (TEAEs).
Measured: 104 +/- 10 days
Period 1 - Adult: Evaluate the pharmacokinetics (PK) of multiple ascending doses of PTH-IA in adults (>= 18 y/o) years old with JMC
To determine PK parameters after multiple ascending doses of PTH-IA.
Measured: 104 +/- 10 days
Period 2 - Adult and Pediatrics: Evaluate the safety and tolerability of PTH-IA in adults and children aged 3-17 years old with JMC.
To assess dose-limiting toxicities (DLTs) and incidence, severity, seriousness, and causality of all treatment-emergent adverse events (TEAEs).
Measured: 28 weeks +/- 10 days
Period 2 - Adult and Pediatrics: Evaluate the pharmacokinetics (PK) of multiple ascending doses of PTH-IA in children aged 3-17 years old with JMC.
To determine PK parameters after multiple ascending doses of PTH-IA.
Measured: 28 weeks +/- 10 days
Period 2 - Adult and Pediatrics: Evaluate the effect of PTH-IA on serum PTH levels in children and adults with JMC.
To evaluate changes in serum PTH from baseline to the end of treatment.
Measured: 28 weeks +/- 10 days
Secondary outcomes (2)
Periods 1 and 2 - Identify the optimal dose range of PTH-IA.
To measure the absolute levels and percentage change: - From baseline in serum-corrected calcium pre- and post-intervention at the end of treatment.- In the ratio of serum-corrected calcium to PTH ([mg/dl]/[pg/ml]) pre- and post-intervention at the end of the study.- From baseline in fractional excretion of calcium at the end of treatment.- From baseline in urine nephrogenous cAMP at the end of treatment.- From baseline in serum phosphate at the end of treatment.- From baseline in markers of mineral homeostasis: 1,25(OH)2 vitamin D and ratio of 1,25(OH)2 vitamin D to PTH at the end of treatment.- To define the minimally effective dose defined by the dose at which the mean of the two highest PTH levels increases to 30-40 pg/mL (in individuals with baseline PTH <= 20 pg/mL) in the absence of DLTs.
Measured: Period 1: 104 +/- 10 days. Period 2: 28 weeks +/- 10 days.
Periods 1 and 2 - Evaluate potential measures of efficacy of PTH-IA in JMC.
To measure the change in: - Tubular reabsorption of phosphate and the ratio of tubular maximum reabsorption of phosphate to GFR between pre- \& post-intervention at the end of treatment.- Bone turnover markers (P1NP, BSALP, CTX, osteocalcin) between pre- \& post-intervention.- Pre-defined sentinel skeletal lesion metabolic activity representing region of most intense pathology as measured by 18F- NaF PET/CT (<= 5 lesions) between pre- \& post-intervention.- Pre-defined target skeletal lesion mineral density representing region of most intense pathology as measured by 18F- NaF PET/CT (<= 5 lesions) between pre- \& post-intervention. - Nephrocalcinosis scores on ultrasound from baseline to end of treatment (0-no nephrocalcinosis to 3-severe).- HR-pQCT parameters of the radius and tibia: total BMD, cortical and trabecular BMD; cortical thickness, cortical porosity, BV/TV, trabecular number, thickness, and separation; stiffness and failure load of the peripheral skeleton.
Measured: Period 1: 104 +/- 10 days. Period 2: 28 weeks +/- 10 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2026
- Study start27 May 2026
- Primary completion1 Jun 2029 (estimated)
- Study completion1 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Jansen's Metaphyseal ChondrodysplasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Alison M Boyce, M.D., Principal investigator, National Institute of Dental and Craniofacial Research (NIDCR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07541209
- Sponsor's protocol ID
- 10001653
- Other IDs
- 001653-D
- Status last verified
- 5 Oct 2026
- First submitted
- 18 Apr 2026
- Last updated
- 19 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: This study will comply with the NIH Data Sharing Policy and the Clinical Trials Registration and Results Information Submission rule.
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Open-label First-in-Human Dose-Escalating Safety and Efficacy Study Evaluating Subcutaneous Administration of PTH-IA in Adults and Children With Jansen s Metaphyseal Chondrodysplasia (JMC)
- ClinicalTrials.gov ID
- NCT07541209
- Acronym / sponsor ID
- 10001653
- Conditions
- Jansen's Metaphyseal Chondrodysplasia
- Keywords
- Jansen Type Metaphyseal Chondrodysplasia, Parathyroid Hormone 1 Receptor (PTH1R), PTH1R Mutations, Parathyroid Hormone-Related Peptide (PTHrP), Parathyroid Hormone Inverse Agonist (PTH-IA)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- National Institute of Dental and Craniofacial Research (NIDCR)US National Institutes of Health
- Study start
- 27 May 2026 (actual)
- Primary completion
- 1 Jun 2029 (estimated)
- Study completion
- 1 Jun 2029 (estimated)
- First posted
- 21 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Description:
This is a Phase 1/2 open-label, single-arm study to evaluate the safety of multiple ascending doses of PTH-IA administered subcutaneously twice a day in individuals with JMC conducted at the National Institutes of Health Clinical Center.
Objectives Primary Objectives
Period 1 - Adult
- Evaluate the safety and tolerability of PTH-IA in adults with JMC (>=18 years)
- Evaluate the pharmacokinetics (PK) of multiple ascending doses of PTH-IA in adults (>= 18 y/o) years old with JMC
Period 2 - Adult and Pediatrics
- Evaluate the safety and tolerability of PTH-IA in adults and children aged 3-17 years old with JMC
- Evaluate the pharmacokinetics (PK) of multiple ascending doses of PTH-IA in children aged 3-17 years old with JMC
- Evaluate the effect of PTH-IA on serum PTH levels on children and adults with JMC
Secondary Objectives
Periods 1 and 2
- Identify the optimal dose range of PTH-IA
- Evaluate potential measures of efficacy of PTH-IA in JMC
Exploratory Objectives
Periods 1 and 2
- Evaluate the effect of PTH-IA on physical function
- Evaluate the effect of PTH-IA on pain and health-related quality of life (QOL)
- Evaluate the immunogenicity of PTH-IA
- Describe the baseline and response to treatment histological characteristics of bone lesions in JMC
Endpoints Primary Endpoints
Period 1
- Dose limiting toxicities (DLTs) and incidence, severity, seriousness, and causality of all treatment-emergent adverse events (TEAEs)
- PK parameters after multiple ascending doses of PTH-IA
Period 2
- Dose limiting toxicities (DLTs) and incidence, severity, seriousness, and causality of all treatment-emergent adverse events (TEAEs)
- PK parameters after multiple ascending doses of PTH-IA
- Change in serum PTH from baseline to end of treatment
Secondary Endpoints
Periods 1 and 2
- Absolute levels and percentage change from baseline in serum corrected calcium pre- and post-intervention at end of treatment
- Absolute levels and change in ratio of serum corrected calcium to PTH ([mg/dl]/[pg/ml]) pre- and post-intervention at end of study
- Absolute levels and percentage change from baseline in fractional excretion of calcium at end of treatment
- Change in tubular reabsorption of phosphate and ratio of tubular maximum reabsorption of phosphate to GFR between pre- and post-intervention at end of treatment
- Absolute levels and percentage change from baseline in urine nephrogenous cAMP at end of treatment
- Absolute levels and percentage change from baseline in serum phosphate at end of treatment
- Change in bone turnover markers (P1NP, BSALP, CTX, osteocalcin) between pre- and post-intervention at end of treatment
- Absolute levels and percentage change from baseline in markers of mineral homeostasis: 1,25(OH)2 vitamin D and ratio of 1,25(OH)2 vitamin D to PTH at end of treatment
- Change in pre-defined sentinel skeletal lesion metabolic activity representing region of most intense pathology as measured by 18F- NaF PET/CT (<= 5 lesions) between pre- and post-intervention at end of treatment
- Change in pre-defined target skeletal lesion mineral density representing region of most intense pathology as measured by 18F- NaF PET/CT (<= 5 lesions) between pre- and postintervention at end of treatment
- Change in nephrocalcinosis scores on ultrasound from baseline to end of treatment (0-no nephrocalcinosis and 3- severe nephrocalcinosis)
- Change in HR-pQCT parameters of the radius and tibia: total BMD, cortical and trabecular BMD; cortical thickness, cortical porosity, BV/TV, trabecular number, thickness, and separation; stiffness and failure load of the peripheral skeleton
- Minimally effective dose defined by dose at which the mean of two highest PTH levels increases to 30-40 pg/mL (in individuals with baseline PTH <= 20 pg/mL) in the absence of DLTs. In individuals with baseline PTH >20 pg/mL, the optimal dose will be the dose at which the mean of two highest PTH obtained increases to 55-65 pg/mL in the absence ofDLTs.
Exploratory Endpoints
Periods 1 and 2
- Change from baseline in range of motion of upper and lower extremities
- Change from baseline in manual muscle strength testing of bilateral upper and lower extremities
- Change from baseline in gait assessment
- Change from baseline in assessment of skeletal bowing
- Change from baseline in walking speed
- Change from baseline in PROMIS pain intensity, pain interference, mobility, and fatigue scores
- Development and characterization of anti-drug antibodies (ADAs)
- JMC lesion histology as assessed by bone biopsies
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with PTH-IA | Experimental | Drug: PTH-IAAll participants will receive PTH-IA for up to 90+/-7 days in Period 1, and 24 weeks +/- 7 days in Period 2. |
Who may qualify
- Ages
- 3 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Willingness of participant and/or guardian to sign a written informed consent form, which must be obtained prior to initiation of study procedures.
- Period 1: Adults >=18 years of age
- Period 2: Adults and children 3-17 years of age
- Minimum body weight of 35 kg for participation in Period 1 and 18 kg for participation in Period 2.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PTH-IAPTH-IA is a 30-amino acid peptide expected to act as an inverse agonist, decreasing the proportion of mutant PTH1R receptors in the active-state conformation and leading to a reduction in basal cAMP signaling. This hypothesis is based on results from PTH-IA treatment of cells and animal models expressing the different PTH1R mutations seen in JMC individuals. In-vitro studies of HEK293 cells stably transfected with a Glosensor cAMP reporter and plasmids expressing the different PTH1R constitutively active mutant JMC alleles (H223R, I458K, I458R, T410P, and T410R) showed that the cells displayed agonist-independent cAMP generation. Treatment of cells expressing the different PTH1R mutations with PTH-IA resulted in a rapid and persistent reduction in basal cAMP signaling, indicating that the peptide can act as an inverse agonist and thus decreases the proportion of mutant receptors in the active-state conformation. | Drug | Treatment with PTH-IA |
Primary outcome
Period 1 - Adult: Evaluate the safety and tolerability of PTH-IA in adults with JMC (>= 18 years)
Time frame: 104 +/- 10 days
To assess dose-limiting toxicities (DLTs) and incidence, severity, seriousness, and causality of all treatment-emergent adverse events (TEAEs).
Period 1 - Adult: Evaluate the pharmacokinetics (PK) of multiple ascending doses of PTH-IA in adults (>= 18 y/o) years old with JMC
Time frame: 104 +/- 10 days
To determine PK parameters after multiple ascending doses of PTH-IA.
Period 2 - Adult and Pediatrics: Evaluate the safety and tolerability of PTH-IA in adults and children aged 3-17 years old with JMC.
Time frame: 28 weeks +/- 10 days
To assess dose-limiting toxicities (DLTs) and incidence, severity, seriousness, and causality of all treatment-emergent adverse events (TEAEs).
Period 2 - Adult and Pediatrics: Evaluate the pharmacokinetics (PK) of multiple ascending doses of PTH-IA in children aged 3-17 years old with JMC.
Time frame: 28 weeks +/- 10 days
To determine PK parameters after multiple ascending doses of PTH-IA.
Period 2 - Adult and Pediatrics: Evaluate the effect of PTH-IA on serum PTH levels in children and adults with JMC.
Time frame: 28 weeks +/- 10 days
To evaluate changes in serum PTH from baseline to the end of treatment.
2 secondary outcomes
Periods 1 and 2 - Identify the optimal dose range of PTH-IA.
Time frame: Period 1: 104 +/- 10 days. Period 2: 28 weeks +/- 10 days.
Periods 1 and 2 - Evaluate potential measures of efficacy of PTH-IA in JMC.
Time frame: Period 1: 104 +/- 10 days. Period 2: 28 weeks +/- 10 days.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. This study will comply with the NIH Data Sharing Policy and the Clinical Trials Registration and Results Information Submission rule.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alison M Boyce, M.D. principal investigator
National Institute of Dental and Craniofacial Research (NIDCR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PTH-IA in people with Jansen's Metaphyseal Chondrodysplasia, run by National Institute of Dental and Craniofacial Research (NIDCR) at 1 site in United States.
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 15 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Olivia J de Jong, C.R.N.P. ((240) 595-2764, olivia.dejong@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Period 1 - Adult: Evaluate the safety and tolerability of PTH-IA in adults with JMC (>= 18 years) (time frame: 104 +/- 10 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Oct 2026.