Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity
Condition: Genetic Obesity; Obesity; Obesity Due to Melanocortin 4 Receptor Deficiency
MeSH terms: Genetic Diseases, Inborn; Obesity
Intervention: Setmelanotide
Intervention description: RM-493 QD SC injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 213.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No
Keywords: Pro-opiomelanocortin (POMC) deficiency obesity; LepR deficiency obesity; Smith-Magenis Syndrome; MC4R deficiency obesity; SRC1 deficiency obesity; SH2B1 deficiency obesity

Summary:

      The purpose of the study was to determine the effect of setmelanotide (RM-493) on weight,
      hunger assessments, and other factors in participants with rare genetic disorders of obesity.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participants with the following genotypes and/or clinical assessment:

               1. POMC/PCSK1/LEPR heterozygous - not currently enrolling new participants

               2. POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or
                  homozygous deficiency obesity

               3. POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more
                  genes) deficiency obesity

               4. SMS

               5. SH2B1 deficiency obesity

               6. Chromosomal rearrangement of the 16p11.2 locus causing obesity

               7. Carboxypeptidase E (CPE) compound heterozygous or homozygous deficiency obesity

               8. Leptin deficiency obesity with loss of response to metreleptin

               9. SRC1 deficiency obesity

              10. MC4R deficiency obesity

          2. Age 6 years and above

          3. Obese, defined as Body Mass Index (BMI) ≥ 30 kilogram per meter square (kg/m^2) for
             participants ≥16 years of age or BMI≥ 95th percentile for age and gender for
             participants 6 up to 16 years of age.

          4. Participant and/or parent or guardian is able to understand and comply with the
             requirements of the study and is able to understand and sign the written informed
             consent/assent

          5. Female participants of childbearing potential must be confirmed non-pregnant, and
             agree to use contraception as outlined in the protocol.

          6. Male participants with female partners of childbearing potential must agree to a
             double barrier method if they become sexually active during the study. Male
             participants must not donate sperm during and for 90 days following their
             participation in the study.

        Key Exclusion Criteria:

          1. Recent intensive (within 2 months) diet and/or exercise regimen with or without the
             use of weight loss agents that has resulted in > 2% weight loss.

          2. Use of any medication that is approved to treat obesity within three months of first
             dose of study drug (e.g., orlistat, lorcaserin, phentermine-topiramate,
             naltrexone-bupropion).

          3. Gastric bypass surgery within the previous six months or any prior gastric bypass
             surgery resulting in >10% weight loss durably maintained

          4. Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive
             disorder, or other psychiatric disorder(s)

          5. Suicidal ideation, attempt or behavior

          6. Clinically significant pulmonary, cardiac, or oncologic disease

          7. hemoglobin A1c (HbA1c) > 9.0% at Screening

          8. History of significant liver disease

          9. Glomerular filtration rate (GFR) < 30 milliliter/minute (mL/min) at Screening.

         10. History or close family history of melanoma or participant history of oculocutaneous
             albinism

         11. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions.

         12. Participation in any clinical study with an investigational drug/device within 3
             months prior to the first day of dosing.

         13. Participants previously enrolled in a clinical study involving setmelanotide or any
             previous exposure to setmelanotide.

         14. Inability to comply with QD injection regimen.

         15. Females who are breastfeeding or nursing.

        Other protocol defined Inclusion/Exclusion criteria may apply.