Phase 2 Study to Evaluate Safety and Efficacy of RM-493 in Obese Participants
Condition: Overweight
MeSH terms: Overweight
Intervention: Setmelanotide; Placebo
Intervention description: Daily subcutaneous infusion; Daily subcutaneous infusion
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Overweight

Summary:

      The purpose of this study is to evaluate the effects of RM-493 on mean percent body weight
      loss, and other weight loss parameters as well as Pharmacokinetic (PK) profile, and
      ambulatory blood pressure in obese participants. The study is designed to evaluate the
      efficacy and tolerability of a single dose of RM-493. The study drug (RM-493 and placebo)
      will be administered subcutaneously in a blinded fashion.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be between the age of 18 and 65.

          2. Able to provide voluntary, written informed consent with comprehension of all aspects
             of the protocol, prior to any study procedures.

          3. In good general health, without significant medical history, physical examination
             findings, or clinical laboratory abnormalities.

          4. Body Mass Index: 35-50 Kg/m^2, inclusive. It is planned that approximately 20 (but no
             more than 50% of the total participants enrolled) of these participants will have a
             BMI ≥ 40 Kg/m^2

          5. Stable body weight (+/- 5 Kg) during previous 6 months.

          6. Blood pressure (<150/95 mmHg); may include stable dose (≥ 30 days of use) of up to two
             anti-hypertensive medications to achieve control that are intended to remain on a
             stable dose during the protocol.

          7. Willingness and demonstrates ability to self-administer study medication
             subcutaneously via an infusion pump during the placebo practice period.

          8. Willing to maintain a healthy diet and exercise regime throughout study as recommended
             by counseling at study start.

          9. Females of childbearing potential must agree to be abstinent or else use any two of
             the following medically acceptable forms of contraception from the Screening Period
             through the completion of study treatment: hormonal, condom with spermicidal jelly,
             diaphragm or cervical cap with spermicidal jelly, or intrauterine device (IUD).
             Hormonal contraception must have started at least 3 months prior to screening. A
             female whose male partner has had a vasectomy must agree to use one additional form of
             medically acceptable contraception. Participants must agree to practice the above
             birth control methods for 30 days after completion of study treatment as a safety
             precaution.

         10. Females of non-childbearing potential, defined as surgically sterile (status post
             hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal
             for at least 12 months (and confirmed with a screening follicle stimulating hormone
             (FSH) level in the post-menopausal range), do not require contraception during the
             study.

         11. Males with female partners of childbearing potential must agree to use two medically
             acceptable forms of contraception as described above, with one of the two forms being
             condom with spermicide, from the Screening Period through 90 days after completion of
             study treatment. Males with female partners of childbearing potential who themselves
             are surgically sterile (status post vasectomy) must agree to use condoms with
             spermicide over the same period of time.

        Exclusion Criteria:

          1. Fasting blood glucose > than 140 mg/dL.

          2. Haemoglobin A1c (HbA1c) ≥6.5%.

          3. Thyroid stimulating hormone (TSH) level outside the normal range.

          4. Creatinine > 1.5 times the upper limit of normal.

          5. Liver function tests > 2 times the upper limit of normal.

          6. Active or history of any significant medical condition including renal, hepatic,
             pulmonary, gastrointestinal, cardiovascular, genitourinary, endocrine, immunologic,
             metabolic, neurologic or hematological disease.

          7. Participants with a history of the following:

               1. Uncontrolled hypertension;

               2. Diabetes requiring medical treatment, presently or in the past;

               3. Major depressive disorder within the last 2 years;

               4. Any lifetime history of a suicide attempt;

               5. Any suicidal behavior in the last month;

               6. Other severe psychiatric disorders (e.g. schizophrenia, bipolar disorder, severe
                  eating disorders including bulimia).

          8. A patient health questionnaire - 9 (PHQ-9) score of ≥15.

          9. Any suicidal ideation of type 4 or 5 on the columbia suicide severity rating scale
             (C-SSRS).

         10. Prior bariatric surgery.

         11. Treated with anorectic agents or drugs with anorexia as a frequent side event.

         12. Taking 3 or more anti-hypertensive medications.

         13. Acute illness or history of illness, which in the opinion of the Investigator, could
             pose a threat or harm to the participant or obscure interpretation of laboratory test
             results or interpretation of study data.

         14. History of human immunodeficiency virus (HIV) infection.

         15. History of significant drug hypersensitivity or anaphylaxis.

         16. History of hypersensitivity to proteins (e.g., allergy shots).

         17. Any clinically significant abnormalities on screening laboratories as determined by
             the Investigator.

         18. Abnormal 12-lead electrocardiogram (ECG) at screening or pre-dose (Day 1), except
             minor deviations deemed to be of no clinical significance by the Investigator. QTc
             must be < 450 ms.

         19. Received any experimental drugs or devices or have participated in a clinical study
             within 30 days prior to dosing.

         20. Hospitalization for surgery within the 3 months prior to screening except for minor
             outpatient procedures, or any planned hospitalizations during the study period.

         21. Poor venous access or inability to tolerate venipuncture.

         22. Inability to attend all study visits or comply with protocol requirements including
             fasting and restrictions on concomitant medication intake.

         23. Participation in weight loss programs during the study period, including nutritional
             supplements/ replacements other than as recommended by nutritional counseling provided
             at study start.

         24. Use of prescription medications on a regular basis with the following exceptions:

               1. Contraceptives (must be on for ≥3 months);

               2. Hormone replacement therapy (must be on stable dose for ≥3 months);

               3. Antihypertensives (<3 medications on a stable dose for ≥ 30 days);

               4. Statins (dose must be ≤ half the maximum dose; must be on a stable dose ≥3
                  months);

               5. Fibrates (must be on stable dose for ≥3 months);

               6. Niacin (must be on stable dose for ≥3 months);

               7. Thyroxin (stable dose for ≥ 30 days);

               8. The last use of any other prescription medication must have been greater than 5
                  half-lives for the specific medication or at least 14 days prior to
                  randomization, whichever is longer.

         25. Women who are pregnant or are breast feeding.

         26. Previously randomized and dosed in this study or previously exposed to RM-493.

         27. History of alcohol or drug abuse within 5 years of Screening Visit.

         28. Any other reason, which in the opinion of the Investigator would confound proper
             evaluation of the study.