Pseudohypoparathyroidism Type 1aPhase 2NCT07496463
Setmelanotide to Treat Obesity in a Patient With Pseudohypoparathyroidism Type 1a (PHP1a)
A Phase 2 study testing Setmelanotide in people with Pseudohypoparathyroidism Type 1a and Obesity, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
The investigators plan to test the efficacy and safey of 6-months of open-label setmelanotide to treat obesity in a single patient with pseudohypoparathyroidism type 1a due to a GNAS mutation. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Pseudohypoparathyroidism Type 1a, Obesity
- What is being tested?
- Setmelanotide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 2026to 30 Apr 2027
- Phase
- Phase 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Known patient with PHP1a (confirmed GNAS mutation)
- Optimized therapy for diabetes and dyslipidemia
Who cannot join
- Use of medications that may affect endpoints that are changed within 3 months prior to Baseline or that are likely to require a change in dose during the open-label treatment period
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
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
The investigators plan to test the efficacy and safey of 6-months of open-label setmelanotide to treat obesity in a single patient with pseudohypoparathyroidism type 1a due to a GNAS mutation.
Read the detailed description
Pseudohypoparathyroidism type 1A (PHP1a) is a rare genetic disorder caused by impaired G-protein signaling due to heterozygous mutations in the gene GNAS. Multiple abnormalities may result including hypocalcemia, hypothyroidism, hypogonadism, and developmental delay. Obesity also commonly occurs due to impaired signaling through the melanocortin-4 receptor (MC4R). The melanocortin-4 receptor agonist setmelanotide has been proposed as a potential yet untested treatment strategy for patients with pathogenic GNAS variants.
In the current study, the investigators plan to test effects of setmelanotide on body weight, body composition, and metabolic parameters in a single patient with PHP1a. GNAS is a paternally imprinted gene, and thus PHP1a results primarily when a mutation is inherited on the preferentially expressed maternal allele. However, detailed studies have shown that 1) GNAS is not imprinted in all areas of the brain, and 2) in regions where imprinting does occur, it is incomplete (e.g., low levels of paternally inherited protein remain expressed). As such, the investigators hypothesize that setmelanotide will augment MC4R signaling by maximally stimulating low levels of intact, paternally inherited GNAS in patients with PHP1a and milder GNAS disorders.
This project stands to identify a novel patient population with rare monogenic obesity who may benefit from setmelanotide therapy and who is classically resistant to mainstream obesity medications. Evidence of clinical benefit in this single patient would serve as proof of concept for a larger scale clinical study of patients with PHP1a and GNAS mutations.
- Conditions
- Pseudohypoparathyroidism Type 1a, Obesity
- Being tested
- Setmelanotide
- Keywords
- pseudohypoparathyroidism type 1a, obesity, setmelanotide
- Medical subject headings
- Pseudohypoparathyroidism, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SetmelanotideDrug
Setmelanotide will be prescribed at the standard initial dose of 2 mg SC daily. The treatment will be uptitrated at the 2-Week visit to 3 mg SC daily if tolerated. We will continue this maximal dose for a period of 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Patient with pseudohypoparathyroidism type 1a | Other | A preselected patient with obesity related to pseudohypoparathyroidism type 1a. Receives: Drug: Setmelanotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Greater than or Equal to 5% Weight loss
Greater than or equal to 5% weight loss from baseline
Measured: Baseline to 6 Months
Secondary outcomes (4)
Percent Weight Loss
Percent change in weight from baseline
Measured: Baseline to 3 Months, Baseline to 6 Months
Trunk Fat Mass
Trunk fat mass measured on dual-energy x-ray absorptiometry scan
Measured: Baseline to 6 Months
Hemoglobin A1c
Hemoglobin A1c (%) measured on blood draw
Measured: Baseline to 3 Months, Baseline to 6 Months
Serum Triglycerides
Serum triglycerides (mg/dL) measured on blood draw
Measured: Baseline to 3 Months, Baseline to 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2026
- Study start21 Jul 2026
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pseudohypoparathyroidism Type 1aStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single patient open-label study
- Masking
- None (open label)
- Enrolment
- 1 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lindsay Fourman, MD, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07496463
- Sponsor's protocol ID
- 2026P000332
- Status last verified
- Jul 2026
- First submitted
- 22 Mar 2026
- Last updated
- 23 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data and biospecimens may be shared.
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Setmelanotide to Treat Obesity in a Patient With Pseudohypoparathyroidism Type 1a (PHP1a)
- ClinicalTrials.gov ID
- NCT07496463
- Acronym / sponsor ID
- 2026P000332
- Conditions
- Pseudohypoparathyroidism Type 1a, Obesity
- Keywords
- pseudohypoparathyroidism type 1a, obesity, setmelanotide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 1 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 21 Jul 2026 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 27 Mar 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.
The investigators plan to test the efficacy and safey of 6-months of open-label setmelanotide to treat obesity in a single patient with pseudohypoparathyroidism type 1a due to a GNAS mutation.
Detailed description
Pseudohypoparathyroidism type 1A (PHP1a) is a rare genetic disorder caused by impaired G-protein signaling due to heterozygous mutations in the gene GNAS. Multiple abnormalities may result including hypocalcemia, hypothyroidism, hypogonadism, and developmental delay. Obesity also commonly occurs due to impaired signaling through the melanocortin-4 receptor (MC4R). The melanocortin-4 receptor agonist setmelanotide has been proposed as a potential yet untested treatment strategy for patients with pathogenic GNAS variants.
In the current study, the investigators plan to test effects of setmelanotide on body weight, body composition, and metabolic parameters in a single patient with PHP1a. GNAS is a paternally imprinted gene, and thus PHP1a results primarily when a mutation is inherited on the preferentially expressed maternal allele. However, detailed studies have shown that 1) GNAS is not imprinted in all areas of the brain, and 2) in regions where imprinting does occur, it is incomplete (e.g., low levels of paternally inherited protein remain expressed). As such, the investigators hypothesize that setmelanotide will augment MC4R signaling by maximally stimulating low levels of intact, paternally inherited GNAS in patients with PHP1a and milder GNAS disorders.
This project stands to identify a novel patient population with rare monogenic obesity who may benefit from setmelanotide therapy and who is classically resistant to mainstream obesity medications. Evidence of clinical benefit in this single patient would serve as proof of concept for a larger scale clinical study of patients with PHP1a and GNAS mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single patient open-label study
| Arm | Type | Receives |
|---|---|---|
| Patient with pseudohypoparathyroidism type 1a | Other | Drug: SetmelanotideA preselected patient with obesity related to pseudohypoparathyroidism type 1a. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Known patient with PHP1a (confirmed GNAS mutation)
- Optimized therapy for diabetes and dyslipidemia
Key exclusion criteria (1 listed)
- Use of medications that may affect endpoints that are changed within 3 months prior to Baseline or that are likely to require a change in dose during the open-label treatment period
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 |
|---|---|---|
| SetmelanotideSetmelanotide will be prescribed at the standard initial dose of 2 mg SC daily. The treatment will be uptitrated at the 2-Week visit to 3 mg SC daily if tolerated. We will continue this maximal dose for a period of 6 months. | Drug | Patient with pseudohypoparathyroidism type 1a |
Primary outcome
Greater than or Equal to 5% Weight loss
Time frame: Baseline to 6 Months
Greater than or equal to 5% weight loss from baseline
4 secondary outcomes
Percent Weight Loss
Time frame: Baseline to 3 Months, Baseline to 6 Months
Trunk Fat Mass
Time frame: Baseline to 6 Months
Hemoglobin A1c
Time frame: Baseline to 3 Months, Baseline to 6 Months
Serum Triglycerides
Time frame: Baseline to 3 Months, Baseline to 6 Months
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 23 Jul 2026.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified data and biospecimens may be shared.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Setmelanotide in people with Pseudohypoparathyroidism Type 1a and Obesity, run by Massachusetts General Hospital 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 2 inclusion and 1 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: enrolling by invitation, as of the sponsor's last update on 23 Jul 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 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?
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?
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?
Greater than or Equal to 5% Weight loss (time frame: Baseline to 6 Months). 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 23 Jul 2026.