Setmelanotide Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity

Sponsor
Rhythm Pharmaceuticals, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03013543
Collaborator
(none)
150
57
1
59
2.6
0

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
150 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity
Actual Study Start Date :
Jan 1, 2017
Anticipated Primary Completion Date :
Nov 1, 2021
Anticipated Study Completion Date :
Dec 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Setmelanotide

Setmelanotide subcutaneous injection once daily

Drug: Setmelanotide
RM-493 once daily subcutaneous injection
Other Names:
  • RM-493
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    Ages Eligible for Study:
    6 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Patients with the following genotypes and/or clinical assessment:

    2. POMC/PCSK1/LEPR heterozygous - not currently enrolling new patients

    3. POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity

    4. POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity - not currently enrolling new patients

    5. Smith-Magenis Syndrome (SMS)

    6. SH2B1 deficiency obesity - not currently enrolling new patients

    7. Chromosomal rearrangement of the 16p11.2 locus causing obesity - not currently enrolling new patients

    8. CPE compound heterozygous or homozygous deficiency obesity

    9. Leptin deficiency obesity with loss of response to metreleptin

    10. SRC1 deficiency obesity - not currently enrolling new patients

    11. 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.

    1. Age 6 years and above.

    2. 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.

    3. 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.

    4. 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.

    5. 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:
    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 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.

    3. 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.

    4. 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.

    1. 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.

    2. 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.

    3. HbA1c >9.0% at Screening

    4. 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.

    5. Glomerular filtration rate (GFR) <30 mL/min at Screening.

    6. 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.

    7. 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.

    1. Patient is, in the opinion of the Study Investigator, not suitable to participate in the study.

    2. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.

    3. Patients previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.

    4. Significant hypersensitivity to any excipient in the study drug.

    5. Inability to comply with QD injection regimen.

    6. Females who are breastfeeding or nursing.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    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.
    Responsible Party:
    Rhythm Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT03013543
    Other Study ID Numbers:
    • RM-493-014
    First Posted:
    Jan 6, 2017
    Last Update Posted:
    Jul 16, 2021
    Last Verified:
    Jul 1, 2021

    Study Results

    No Results Posted as of Jul 16, 2021