Specific Gene Defects in the Melanocortin-4 Receptor Pathway, responsible for improper functions of certain messenger materials in the body. E.g Melanocyte-Stimulating Hormone (MSH)
Conditions
Interventions
Trade Name: IMCVIREE
Product Name: Setmelanotide
Product Code: RM-493
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Setmelanotide
CAS Number: 920014-72-8
Current Sponsor code: RM-49
Sponsors
Rhythm Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have a pre-identified: • Heterozygous genetic variant in the POMC gene or PCSK1 gene (Sub-study 35a) • Heterozygous genetic variant in the LEPR gene (Sub-study 35b), • Homozygous or heterozygous variant, compound heterozygous in the SRC1 (Sub-study 35c), • Homozygous or heterozygous variant, compound heterozygous in SH2B1 gene, or chromosomal16p11.2 deletion encompassing the SH2B1 gene (Sub-study 35d), • Heterozygous N221D (Sub-study 35e) variant in the PCSK1 gene. For POMC, PCSK1, LEPR, SRC1 and SH2B1 gene variants, to be considered for inclusion, the variant must either: • be categorized by a CLIA/CAP/ISO15189-certified laboratory using ACMG criteria as a) Pathogenic; or b) Likely Pathogenic; or c) a Variant of Uncertain Significance (VOUS) OR • be an N221D variant of the PCSK1 gene If a patient has composite heterozygous variants eligible for the study she/he will be accounted for the higher category based on ACMG classification. • For example, if a patient is a composite heterozygous for POMC pathogenic variant, and LEPR VOUS, the patient will be categorized as POMC pathogenic (Sub-study 35a). If the 2 variants have the same ACMG classification, adjudication will be assigned to the less prevalent gene sub-study. • For example, if a patient is a composite heterozygous for LEPR VOUS and SRC1 VOUS, the patient will be categorized as SRC1 (Sub-study35c). The final Sub-study assignment will follow this hierarchy: deletion> pathogenic> likely pathogenic> VOUS> RISK. Patients that harbor RISK variants are not eligible, with the exception of PCSK1 N221D . If a patient has two variants with the same ACMG classification, adjudication will be assigned following this arbitrary hierarchy: PCSK1>SRC1>SH2B1>LEPR>POMC>PCSK1 N221D. If the investigator has genetics results on a patient who may be eligible for the study, but the genetics have not yet been categorized by a CLIA/CAP/ISO15189 certified laboratory, then Rhythm may provide testing and/or categorization through a third-party laboratory. 2. Between 6 and 65 years of age at the time of provision of informed consent/assent. 3. Obese, defined as BMI =30 kg/m2 for patients =18 years of age or BMI =95th percentile for age and gender for patients 5 up to 17 years of age, based on based on the United States (US) Centers for Disease Control and Prevention criteria. 4. Patient and/or parent or guardian is able to communicate well with the Investigator, understand and comply with the requirements of the study (including once daily [QD] injection regimen and all other study procedures), and is able to understand and sign the written informed consent/assent. Patients who are unable to comply with all study procedures due to cognitive limitations or any other reason should not be enrolled into the study. 5. Patient and/or parent or guardian reports that patient experienced childhood obesity, defined as the patient and/or parent or guardian reporting that the patient was significantly overweight during childhood. 6. For women of child-bearing potential (WOCBP), agrees to use a highly effective form of contraception throughout the study and for 90 days following the study. • Highly effective forms of contraception include: - Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal) - Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, inje
Exclusion criteria
Exclusion criteria: 1. Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that has resulted in >2% weight loss. 2. Use of any medication that is approved to treat obesity within 3 months of first dose of study (e.g., orlistat, phentermine-topiramate, naltrexone-bupropion, GLP-1 treatments) if >2% weight loss in the last 3 months. 3. History of bariatric surgery with evidence of weight loss of >2% in the last 3 months. 4. Documented diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder or other significant psychiatric disorder(s) that the Investigator believes will interfere significantly with study compliance. 5. Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) during Screening, any suicide attempt in the past 5 years, or any suicidal behavior in the last month. 6. Current, clinically significant pulmonary, cardiac or oncologic disease considered severe enough to interfere with the study and/or confound the results. Any patient with a potentially clinically significant disease should be reviewed with Rhythm to determine eligibility. 7. Glycated hemoglobin (HbA1C) >10% at Screening. 8. History of significant liver disease other than non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). 9. Glomerular filtration rate (GFR) <30 mL/min bat Screening. 10. History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism. 11. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion), determined as part of a comprehensive skin evaluation performed by the Investigator during Screening. Any concerning lesions identified during Screening will be biopsied and results known to be benign prior to enrollment. If the pre-treatment biopsy results are of concern, the patient may need to be excluded from the study. 12. Patient is, in the opinion of the Study Investigator, not suitable to participate in the study. 13. Participation in any clinical study with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first day of dosing. 14. Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide. 15. Significant hypersensitivity to any excipient in the study drug. 16. If female, pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the proportion of obese patients who respond to setmelanotide at 52 weeks of treatment;Secondary Objective: • To evaluate the change in body weight in response to setmelanotide from baseline to 52 weeks of treatment • To evaluate changes in hunger score in response to setmelanotide from baseline to 52 weeks of treatment • To evaluate change in BMI and waist circumference in response to setmelanotide from baseline to 52 weeks of treatment • To evaluate the safety and tolerability of setmelanotide Other Secondary: • To evaluate quality of life parameters following treatment with setmelanotide;Primary end point(s): To evaluate the proportion of obese patients who respond to setmelanotide at 52 weeks of treatment;Timepoint(s) of evaluation of this end point: • Proportion of patients who are responders to active treatment compared to placebo: - For patients =18 years old at the time of enrollment, a responder is defined as achieving a =10% reduction in body weight at 52 weeks of treatment - For patients <18 years old at the time of enrollment, a responder is defined as reduction of body mass index (BMI) =5% at 52 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary: • To evaluate the change in body weight in response to setmelanotide from baseline to 52 weeks of treatment • To evaluate changes in hunger score in response to setmelanotide from baseline to 52 weeks of treatment • To evaluate change in BMI and waist circumference in response to setmelanotide from baseline to 52 weeks of treatment • To evaluate the safety and tolerability of setmelanotide Other Secondary: • To evaluate quality of life parameters following treatment with setmelanotide ;Timepoint(s) of evaluation of this end point: • The mean change and mean percent change in body weight in patients in response to setmelanotide at 52 weeks of treatment compared to placebo • Change in % Centers for Disease Control and Prevention (CDC) 95th percentile in patients 40 at 52 weeks of treatment compared to placebo • Mean body weight loss, and % body weight loss in responders (defined as patients with =5% body weight loss (if >18 years of age), and a decrease in % BMI by 3% (if <18 years of age) after 12 weeks of therapy on 3.0 mg/day or maximally tolerated dose, as compared to placebo responders • Mean percent change in the weekly average most hunger score at 52 weeks of setmelanotide treatment compared to placebo. See in protocol synopsis rest of Timepoints of evaluation due to lack of charchters | — |
Countries
Belgium, Canada, Denmark, France, Germany, Greece, Israel, Italy, Netherlands, Saudi Arabia, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Operations
Rhythm Pharmaceuticals Inc.
Outcome results
None listed