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

Conditions:Obesity Weight Loss, Women's Studies
Therapuetic Areas:Endocrinology, Reproductive
Age Range:12 - Any
Start Date:January 2017
End Date:August 2021
Contact:Sarah Pilley

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Setmelanotide (RM-493) Phase 2 Treatment Trial in Patients With Rare Genetic Disorders of Obesity

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,
including POMC deficiency, LepR deficiency, Bardet-Biedl syndrome and Alström syndrome.

Inclusion Criteria:

1. Rare genetic disease patients genetically confirmed diagnoses (may be confirmed by
test at Screening) of:

1. Homozygous or compound heterozygous (different gene mutation on both alleles)
LEPR mutations

2. Heterozygous POMC mutations

3. POMC hypermethylation (epigenetic) variants (>51.92 % POMC methylation intensity
at the specific analyzed POMC region)

4. Bardet-Biedl Syndrome (BBS)

5. Alström Syndrome

6. LEPR Heterozygous Deficiency Obesity

7. Bi-allelic, homozygous or compound heterozygous (a different gene mutation on
each allele) genetic status for either the POMC, PCSK1, or LEPR genes, with the
loss-of-function (LOF) variant for each allele conferring a severe obesity

8. Smith-Magenis Syndrome (SMS)

2. Age 12 years and above.

3. If adult age ≥18 years, obesity with body mass index (BMI) ≥ 30 kg/m2; if age 12 and
above, obesity with weight > 97th percentile for age and sex on growth chart

4. 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 be able
to understand and sign the written informed consent/assent.

5. 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 FSH level in the post-menopausal lab range), or
delayed pubertal development and failure to have achieved menarche, do not require
contraception during the study.

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 patients
must not donate sperm during and for 90 days following their participation in the

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. Patients may be reconsidered approximately 1 month after cessation of
such intensive regimens.

2. Recent (within 1 month) participation in another clinical trial that would confound
the results of this study.

3. 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 Rhythm prior to

4. 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. Neurocognitive disorders
affecting ability to consent will not be disqualifying as long as an appropriate
guardian able to give consent has been appointed.

5. A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 in subjects with no significant
neurocognitive deficits.

6. Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale
(C-SSRS). Any lifetime history of a suicide attempt, or any suicidal behavior in the
last month, again in patients without evidence of significant neurocognitive

7. Current, clinically significant pulmonary, cardiac, or oncologic disease, if these
were 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.

8. History of significant liver disease or liver injury, or current liver assessment for
a cause of abnormal liver tests [as indicated by abnormal liver function tests,
alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, or
serum bilirubin (> 1.5 x upper limit of normal (ULN) for any of these tests)] for an
etiology other than non-alcoholic 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 will be exclusionary, but
the presence of NAFLD would not be exclusionary.

9. History or presence of impaired renal function as indicated by clinically significant
abnormal creatinine, blood urea nitrogen (BUN), or urinary constituents (e.g.,
albuminuria) or moderate to severe renal dysfunction as defined by the Cockroft Gault
equation < 30 mL/min (Appendix 0).

10. History or close family history (parents or siblings) of skin cancer or melanoma, or
patient history of ocular-cutaneous albinism.

11. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions,
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.

12. Volunteer is, in the opinion of the Study Investigator, not suitable to participate in
the study.

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

14. Significant hypersensitivity to study drug.

15. Inability to comply with QD injection regimen.

16. Females who are breastfeeding or nursing.

Inclusion criteria for extensions after 3 months of treatment:

1. Patient completes the initial ~3 months of treatment period without evidence of severe
or clinically relevant adverse events, changes in vital signs, or changes in safety
laboratories or ECGs

2. Patient loses ~5 kg (or 5% if baseline body weight < 100 kg) of weight over the
treatment period.
We found this trial at
12605 East 16th Avenue
Aurora, Colorado 80045
Principal Investigator: Neda Rasouli, MD
Phone: 720-848-5596
University of Colorado Hospital, Site Top medical professionals, superior medicine and progressive change make University...
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Principal Investigator: Christopher Still, MD
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Principal Investigator: Jennifer Miller, MD
Phone: 352-294-5280
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Principal Investigator: Constance Brown
Phone: 702-889-0061
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Los Angeles, California 90036
Principal Investigator: Lydie Hazan
Phone: 310-289-8242
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Los Angeles, California
Principal Investigator: Patrick Clark
Phone: 213-484-0180
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Principal Investigator: Robert M Haws, MD
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Principal Investigator: Ashley Shoemaker
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Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai is...
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