Setmelanotide Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity
Study Details
Study Description
Brief Summary
The purpose of the study is to determine the effect of setmelanotide (RM-493) on weight, hunger assessments and other factors in patients with rare genetic disorders of obesity.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2/Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Setmelanotide Setmelanotide subcutaneous injection once daily |
Drug: Setmelanotide
RM-493 once daily subcutaneous injection
Other Names:
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Outcome Measures
Primary Outcome Measures
- Effect of Setmelanotide on Body Weight Reduction [1 year]
The proportion of patients in each subgroup of RGDO who achieve at least 5% body weight reduction from baseline, at ~3 months treatment with setmelanotide.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients with the following genotypes and/or clinical assessment:
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POMC/PCSK1/LEPR heterozygous - not currently enrolling new patients
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POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity
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POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity - not currently enrolling new patients
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Smith-Magenis Syndrome (SMS)
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SH2B1 deficiency obesity - not currently enrolling new patients
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Chromosomal rearrangement of the 16p11.2 locus causing obesity - not currently enrolling new patients
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CPE compound heterozygous or homozygous deficiency obesity
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Leptin deficiency obesity with loss of response to metreleptin
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SRC1 deficiency obesity - not currently enrolling new patients
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MC4R deficiency obesity - not currently enrolling new patients
Note: The specific genotype for all patients must be reviewed by the Sponsor prior to study enrollment to confirm that the patient meets Inclusion Criterion #1. In addition, enrollment of patients in some subgroups may be prioritized by the Sponsor in order to ensure enrollment of patients with (1) well described, loss-of-function genetic mutations, (2) a variety of genetic variants, or (3) genetic variants likely to respond to setmelanotide.
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Age 6 years and above.
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Obese, defined as Body Mass Index (BMI) ≥ 30 kg/m2 for patients ≥16 years of age or BMI≥ 95th percentile for age and gender for patients 6 up to 16 years of age.
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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 is able to understand and sign the written informed consent/assent.
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Female participants of child-bearing potential must be confirmed non-pregnant, and 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), post-menopausal for at least 12 months (and confirmed with a screening Follicle-Stimulating Hormone [FSH] level in the post-menopausal lab range), and failure to have achieved menarche, do not require contraception during the study.
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Male participants with female partners of childbearing potential must agree to a doublebarrier method if they become sexually active during the study. Male patients must not donate sperm during and for 90 days following their participation in the study.
Exclusion Criteria:
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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.
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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). Note:Glucagon-like peptide-1 (GLP-1) receptor agonists may be used up to the dose approved for the treatment of diabetes mellitus (e.g., liraglutide up to a daily dose of 1.8 mg) as long as (1) is it not being prescribed for the treatment of obesity, (2) the dose has been stable for at least three months prior to enrollment, (3) the patient has not experienced weight loss during the previous three months, AND (4) the patient intends to keep the dose stable throughout the course of the study.
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Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in >10% weight loss durably maintained from the baseline pre-operative weight with no evidence of weight regain. Specifically, patients may be considered if surgery was not successful, or resulted in <10% weight loss compared to pre-operative baseline weight or clear evidence of weight regain after an initial response to bariatric surgery. All patients with a history of bariatric surgery must be discussed with and receive approval from the Sponsor prior to enrollment.
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Diagnosis of schizophrenia, bipolar disorder, personality disorder or other psychiatric disorder(s) that the Investigator believes will interfere significantly with study compliance.
Neurocognitive disorders affecting ability to consent will not be disqualifying as long as an appropriate guardian able to give consent has been appointed.
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A PHQ-9 score of ≥ 15 or any suicidal ideation of type 4 or 5 on the C-SSRS during Screening, 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 allowed to enroll in the study, as long as in the opinion of the Primary Investigator there are no clinical signs or symptoms of suicidal behavior.
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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 the Sponsor to determine eligibility.
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HbA1c >9.0% at Screening
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History of significant liver disease or abnormal liver tests on Screening (i.e. > 1.5 x upper limit of normal [ULN] for alanine transaminase [ALT], aspartate transaminase [AST], alkaline phosphatase, or serum bilirubin). Note: Patients entering the study with SRC1 haploinsufficiency obesity must be evaluated during the Screening Period for hepatic fibrosis by appropriate imaging techniques (e.g., transient elastography or magnetic resonance elastography). Any patient with moderate or greater fibrosis (e.g., the equivalent of a METAVIR score ≥ 2) will be excluded from the study. Note: A patient with a diagnosis of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) may be allowed to enroll in the study, after consultation with the Sponsor. Other significant liver disease, such as cirrhosis, are exclusionary.
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Glomerular filtration rate (GFR) <30 mL/min at Screening.
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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.
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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 a qualified dermatologist during Screening.
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.
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Patient is, in the opinion of the Study Investigator, not suitable to participate in the study.
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Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
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Patients previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
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Significant hypersensitivity to any excipient in the study drug.
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Inability to comply with QD injection regimen.
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Females who are breastfeeding or nursing.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Synexus Clinical Research US, Inc. - Simon Williamson Clinic, PC | Birmingham | Alabama | United States | 35211 |
2 | Synexus Clinical Research US, Inc. - Phoenix Southeast | Chandler | Arizona | United States | 85224 |
3 | Synexus Clinical Research US, Inc. - Central Arizona Medical Associates, PC | Mesa | Arizona | United States | 85206 |
4 | Honor Health Research Institute | Scottsdale | Arizona | United States | 85258 |
5 | Axis Clinical Trials-Downtown | Los Angeles | California | United States | 90017 |
6 | Axis Clinical Trials Headquarters | Los Angeles | California | United States | 90036 |
7 | San Diego Wake Research | San Diego | California | United States | 92108 |
8 | Anschutz Health and Wellness Center University of Colorado Anschutz Medical Campus | Aurora | Colorado | United States | 80045 |
9 | Division of Endocrinology and Diabetes Children's National Hospital | Washington | District of Columbia | United States | 20010 |
10 | University of Florida College of Medicine | Gainesville | Florida | United States | 32610 |
11 | AXIS South Florida Clinical Trials | Hialeah | Florida | United States | 33016 |
12 | Florida Hospital | Orlando | Florida | United States | 32804 |
13 | Synexus Clinical Research US, Inc. - St. Petersburg | Pinellas Park | Florida | United States | 33781 |
14 | Synexus Clinical Research US, Inc. - Chicago | Chicago | Illinois | United States | 60602 |
15 | Maine Medical Partners | Portland | Maine | United States | 04102 |
16 | NIH Hatfield Clinical Research Center | Bethesda | Maryland | United States | 20892 |
17 | Baystate Medical Center | Springfield | Massachusetts | United States | 01107 |
18 | University of Michigan Medicine | Ann Arbor | Michigan | United States | 48105 |
19 | Precision Medicine for Obesity Research: Gastroenterology & Hepatology Mayo Clinic | Rochester | Minnesota | United States | 55905 |
20 | Washington University St. Louis | Saint Louis | Missouri | United States | 63110 |
21 | Impact Clinical Trials | Las Vegas | Nevada | United States | 89106 |
22 | AXIS New York Clinical Trials | Brooklyn | New York | United States | 11201 |
23 | University at Buffalo | Buffalo | New York | United States | 14203 |
24 | AXIS Clinical Trials | New York | New York | United States | 10022 |
25 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10025 |
26 | Columbia University | New York | New York | United States | 10032 |
27 | Duke University Medical Center | Durham | North Carolina | United States | 27705 |
28 | Wake Research Inc. | Raleigh | North Carolina | United States | 27612 |
29 | Synexus Clinical Research US, Inc. - Akron | Akron | Ohio | United States | 44311 |
30 | Synexus Clinical Research US, Inc. - Cincinnati | Cincinnati | Ohio | United States | 45236 |
31 | Synexus Clinical Research US, Inc. - Columbus | Columbus | Ohio | United States | 43016 |
32 | Obesity Institute, Geisinger Clinic | Danville | Pennsylvania | United States | 17822 |
33 | Childrens Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
34 | Synexus Clinical Research US, Inc. - Primary Care Associates, PC | Anderson | South Carolina | United States | 29621 |
35 | Wake Research TN | Chattanooga | Tennessee | United States | 37421 |
36 | Le Bonheur Children's Hospital | Memphis | Tennessee | United States | 38103 |
37 | Vanderbilt University School of Medicine | Nashville | Tennessee | United States | 37212-3157 |
38 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
39 | Synexus Clinical Research US, Inc. - Plano | Plano | Texas | United States | 75093 |
40 | Synexus Clinical Research US, Inc. - San Antonio | San Antonio | Texas | United States | 78229 |
41 | University of Utah | Salt Lake City | Utah | United States | 84132 |
42 | Seattle Children's Research Institute | Seattle | Washington | United States | 98101 |
43 | Marshfield Clinic Research Institute | Marshfield | Wisconsin | United States | 54449 |
44 | University of Alberta | Edmonton | Canada | T6G 2E1 | |
45 | Hopital Trousseau - Nutrition et Gastroentérologie | Paris | France | 75012 | |
46 | Service de pédiatrie CHU de la Réunion - Hôpital Félix Guyon | Saint-Denis | France | 97405 | |
47 | Charité Berlin | Berlin | Germany | 13354 | |
48 | University of Leipzig | Leipzig | Germany | 04103 | |
49 | University of Ulm | Ulm | Germany | 89075 | |
50 | University General Hospital of Patras | Río | Patras | Greece | 26504 |
51 | Edmond and Lily Safra Children's Hospital | Ramat Gan | Israel | 52621 | |
52 | Erasmus MC | Rotterdam | Netherlands | 3015 CE | |
53 | Hospital Infantil Universitario Niño Jesús | Madrid | Spain | 65 28009 | |
54 | University Hospitals Birmingham NHS Foundation Trust | Birmingham | United Kingdom | B15 2TH | |
55 | Addenbrooke's Hospital | Cambridge | United Kingdom | CB2 0QQ | |
56 | Hammersmith Hospital | London | United Kingdom | W12 0NN | |
57 | Hammersmith Hospital | London | United Kingdom |
Sponsors and Collaborators
- Rhythm Pharmaceuticals, Inc.
Investigators
- Study Chair: Murray Stewart, BM/DM, Rhythm Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RM-493-014