Obesity Associated With Defects in Leptin-melanocortin Pathway
Conditions
Keywords
setmelanotide, RM-493, obesity, leptin-melanocortin, melanocortin 4 receptor
Brief summary
This was a long-term extension trial to study the safety and tolerability of continued setmelanotide treatment in participants who had completed a previous clinical trial on treatment with setmelanotide for obesity associated with genetic defects upstream of the Melanocortin-4 (MC4) receptor in the leptin-melanocortin pathway.
Detailed description
The primary objectives of this extension trial were to explore the long-term safety and tolerability of setmelanotide for up to 7 years or until drug was otherwise available through authorized use. Participants entered this protocol immediately upon completion of their index protocol such that dosing of setmelanotide continued without gaps in therapy.
Interventions
DRUGSetmelanotide
Once daily subcutaneous injection
Sponsors
Rhythm Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label treatment
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Participants aged 2 or older (or aged \>2 years as per local regulations) who had completed participation in a previous setmelanotide trial and demonstrated adequate safety and meaningful clinical benefit (efficacy) 2. Participant and/or parent or guardian was able to communicate with the investigator, understand and sign the written informed consent/assent, and comply with the trial requirements 3. Agree to use a highly effective form of contraception throughout the trial Key
Exclusion criteria
1. Pregnant and/or breastfeeding women 2. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion) 3. Current, clinically significant disease 4. Documented diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s) 5. Suicidal ideation, attempt or behavior 6. History of significant liver disease 7. Moderate to severe renal dysfunction as defined by a glomerular filtration rate (GFR)\<30 milliliters per minute (mL/min). 8. History or close family history of melanoma or participant history of oculocutaneous albinism Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose up to 5.6 years | An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A TEAE was defined as any AE that began or worsened in intensity on or after the date of the first administration of study drug. |
Countries
Canada, France, Germany, Greece, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants from previous index trials (RM-493-011\[NCT02507492\], RM-493-012 \[NCT02896192\], RM-493-014\[NCT03013543\], RM-493-015 \[NCT03287960\], RM-493-023 \[NCT03746522\], RM-493-030 \[NCT04725240\], RM-493-034 \[NCT04963231\] with rare genetic, syndromic, or acquired diseases of obesity upstream of the Melanocortin-4 receptor (MC4R) in the melanocortin-leptin pathway and other abnormalities of the MC4R pathway and wished to continue with setmelanotide treatment were enrolled in this extension trial.
Pre-assignment details
A total of 205 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Setmelanotide Participants received setmelanotide at the same starting dose as received in the index trials as a SC injection once daily for up to 5.6 years in this extension trial. | 205 |
| Total | 205 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Discontinued by Sponsor | 40 |
| Overall Study | Lack of Efficacy | 18 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Miscellaneous | 6 |
| Overall Study | Non-Compliance with Study Drug | 4 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Withdrawal by Parent/Guardian | 6 |
| Overall Study | Withdrawal by Subject | 24 |
Baseline characteristics
| Characteristic | Setmelanotide |
|---|---|
| Age, Continuous | 22.7 Years STANDARD_DEVIATION 14.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 171 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 24 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 24 Participants |
| Race (NIH/OMB) White | 167 Participants |
| Sex: Female, Male Female | 125 Participants |
| Sex: Female, Male Male | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 205 |
| other Total, other adverse events | 198 / 205 |
| serious Total, serious adverse events | 27 / 205 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A TEAE was defined as any AE that began or worsened in intensity on or after the date of the first administration of study drug.
Time frame: From first dose up to 5.6 years
Population: SAS included all participants who received at least one dose of received at least 1 dose of setmelanotide in this extension trial.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Setmelanotide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 198 Participants |