Long Term Extension Trial of Setmelanotide

• ClinicalTrials.gov Identifier: NCT03651765
• Recruitment Status: Recruiting
• First Posted: August 29, 2018
• Last Update Posted: February 17, 2021
• Sponsor: Rhythm Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Rhythm Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: January 18, 2018
• First Posted Date: August 29, 2018
• Last Update Posted Date: February 17, 2021
• Actual Study Start Date: July 15, 2018
• Estimated Primary Completion Date: March 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2018)

Safety and tolerability of setmelanotide [ Time Frame: 2 years ]

Frequency and severity of adverse events (AEs) as well as changes in physical examinations, electrocardiograms (ECGs), vital signs (including resting BP and HR), laboratory evaluations, and injection site reactions.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 27, 2018)

• Weight Loss [ Time Frame: 2 years ]
  Maintenance or continued weight loss
• Hunger [ Time Frame: 2 years ]
  Assessment of hunger using a Hunger Questionnaire
• Body Fat Mass [ Time Frame: 2 years ]
  Assessment of body composition as measured by bioelectrical impedance (BIA) or Dual-energy x-ray absorptiometry (DXA)
• Waist circumference [ Time Frame: 2 years ]
  Assessment of waist circumference
• Percent change in total body mass, non-bone lean mass, and bone density [ Time Frame: 2 years ]
  Percent change in total body mass, non-bone lean mass, and bone density measured in kg and waist circumference .
• Lipid Labs [ Time Frame: 2 years ]
  Changes in fasting lipids
• Assessment of Quality of Life [ Time Frame: 2 years ]
  Assessment of quality of life measured by quality of life questionnaires (IWQOL for adults and PEDSQL for pediatrics)
• Assessment of Health Status [ Time Frame: 2 years ]
  Assessment of health status measured by the SF-36 questionnaire
• Biomarker Assays [ Time Frame: 2 years ]
  Assays to be collected and analyzed: LH, FSH, TSH, free T4, IGF-1, IGFBP-3, Serum procollagen type 1 N-propeptide, COOH-terminal telopeptide of type 1 collagen, N-terminal telopeptide of type 1 collagen, Bone-specific alkaline phosphatase, osteocalcin.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long Term Extension Trial of Setmelanotide
• Official Title: Long Term Extension Trial of Setmelanotide (RM-493) for Patients Who Have Completed a Trial of Setmelanotide for the Treatment of Obesity Associated With Genetic Defects Upstream of the MC4 Receptor in the Leptin-melanocortin Pathway
• Brief Summary: This is a long-term extension trial to study the safety and tolerability of continued setmelanotide treatment in patients who have completed a previous clinical trial on treatment with setmelanotide for obesity associated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway.
• Detailed Description: The purpose of this protocol is to continue the assessment of setmelanotide treatment in patients who have successfully completed all critical study evaluations in a prior trial (index protocol) of setmelanotide for the treatment of obesity associated with genetic defects in the leptin-melanocortin pathway upstream of the MC4 receptor. The primary objectives of this extension trial are to explore the long-term safety and tolerability of setmelanotide for up to 5 years or until drug is otherwise available through authorized use. Patients can enter this protocol immediately upon completion of their index protocol such that dosing of setmelanotide continues without gaps in therapy.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Open label treatment

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Obesity Associated With Defects in Leptin-melanocortin Pathway

Intervention

Drug: Setmelanotide

Once daily subcutaneous injection

Other Name: RM-493

Study Arms

Experimental: Setmelanotide

Once daily subcutaneous injection

Intervention: Drug: Setmelanotide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 29, 2020): 150
• Original Estimated Enrollment (submitted: August 27, 2018): 100
• Estimated Study Completion Date: March 2023
• Estimated Primary Completion Date: March 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients aged 6 or older that have completed participation on active drug and demonstrated adequate safety and meaningful clinical benefit (efficacy) in a previous setmelanotide study for obesity associated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway.

   Note: The index study may have a primary endpoint relied on efficacy, safety or tolerability. Patient will be eligible for extension study if the Primary Investigator believes the patient exhibited a clinically meaningful benefit (i,e, efficacy) to setmelanotide treatment, and would benefit from continued treatment, after discussion with the Sponsor.

2. Study participant and/or parent or guardian is able to communicate well with the investigator, to understand and comply with the requirements of the study, and to understand and sign the written informed consent/assent. The patient must assent/consent to participate in the trial.
3. Female participants of child-bearing potential must agree to use contraception as outlined in the protocol. Female participants of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation), postmenopausal for at least 12 months (and confirmed with a screening FSH level in the postmenopausal lab range), or have delayed pubertal development and failure to have achieved menarche, do not require contraception during the study. Any female participant in this latter category of having failed to reach menarche upon study entry and who now suspects this status may have changed should promptly inform the investigator and undergo pregnancy testing. All patients must agree to follow requirements for contraception outlined in the protocol.

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), determined as part of a screening comprehensive skin evaluation performed by a qualified dermatologist. Any concerning lesions identified during the screening period 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.
3. Patient is, in the opinion of the Study Investigator, not suitable to participate in the study. In addition, any patient who experiences a gap in treatment of at least one month between completing the Index study and Screening for this study, should have the following exclusion criteria evaluated:
4. Current, clinically significant disease, if severe enough to interfere with the study and/or would confound the results. Any such patients should be discussed with the Sponsor prior to inclusion
5. Diagnosis of schizophrenia, bipolar disorder, personality disorder or other Diagnostic and Statistical Manual of Mental Disorders (DSM-III) disorders that the investigator believes will interfere significantly with study compliance.
6. A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15.
7. Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS). Any lifetime history of a suicide attempt, or any suicidal behavior in the last month. Note: Patients who are unable to complete the PHQ-9 or C-SSRS due to significant neurocognitive defects may be enrolled in the study, as long as in the opinion of the Primary Investigator there are no clinical signs or symptoms of suicidal behavior.
8. History of significant liver disease or liver injury, or a current liver assessment due to abnormal liver tests (as indicated by abnormal liver function tests, alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase, or serum bilirubin >1.5× the upper limit of normal [ULN] for any of these tests) for an etiology other than nonalcoholic fatty liver disease (NAFLD). Thus, any underlying etiology besides NAFLD, including diagnosed non-alcoholic steatohepatitis (NASH), other causes of hepatitis, or history of hepatic cirrhosis is exclusionary, but the presence of NAFLD is not be exclusionary.
9. Moderate to severe renal dysfunction as defined by a glomerular filtration rate (GFR) <30 mL/min.
10. History or close family history (parents or siblings) of skin cancer or melanoma (not including non-invasive/infiltrative basal or squamous cell lesion), or patient history of ocular-cutaneous albinism.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Olga Ohayon; 8572644289; oohayon@rhythmtx.com

• Listed Location Countries: Canada, Germany, Netherlands, United Kingdom, United States

Administrative Information

• NCT Number: NCT03651765
• Other Study ID Numbers: RM-493-022
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Rhythm Pharmaceuticals, Inc.
• Study Sponsor: Rhythm Pharmaceuticals, Inc.
• Collaborators: Not Provided

Investigators

• Study Chair: Murray Stewart, MD; Rhythm Pharmaceuticals, Inc.

• PRS Account: Rhythm Pharmaceuticals, Inc.
• Verification Date: February 2021