Setmelanotide (RM-493) trial in Bardet-Biedl Syndrome (BBS) and AlstrC6m syndrome (AS) Patients with Moderate to Severe Obesity
- Conditions
- Obesity and hyperphagia in patients with Bardet-Biedl Syndrome or AlstrC6m syndromeTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-004058-11-ES
- Lead Sponsor
- Rhythm Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 52
1. BBS clinical diagnosis as per Beales, 1999 (with either 4 primary features or 3 primary and 2 secondary features, as described below):
- Primary Diagnostic Criteria
• Rod cone dystrophy
• Learning disabilities
• Polydactyly
• Hypogonadism in males
• Obesity
• Renal anomalies
- Secondary Diagnostic Criteria:
• Speech disorder/delay
• Mild spasticity (especially lower limbs)
• Strabismus/cataracts/astigmatism
• Diabetes mellitus
• Brachydactyly/syndactyly
• Dental crowding/hypodontia/small roots/high arched palate
• Developmental delay
• Left ventricular hypertrophy/congenital heart disease
• Polyuria/polydipsia (nephrogenic diabetes insipidus)
• Hepatic fibrosis
• Ataxia/poor coordination
Or AS diagnosis as per Marshall, 2007 (using major and minor age adjusted criteria, as described below).
For patients 6 to b$14 years of age - Minimum Required: 2 major criteria or 1 major and 3 minor criteria, as follow:
- Major Diagnostic Criteria
• Mutation of ALMS1 and/or family history of AS
• Vision (nystagmus, photophobia, diminished acuity, if old enough for testing: cone dystrophy by ERG)
- Minor Diagnostic Criteria
• Obesity and/or insulin resistance and/or T2DM
• History of DCM/CHF
• Hearing loss
• Hepatic dysfunction
• Renal failure
• Advanced bone age
For patients b%15 years of age - Minimum Required: 2 major and 2 minor criteria or 1 major and 4 minor criteria, as listed below:
- Major Diagnostic Criteria:
• Mutation of ALMS1 and/or family history of AS
• Vision (history of nystagmus in infancy/childhood, legal blindness, cone and rod dystrophy by ERG)
- Minor Diagnostic Criteria:
• Obesity and/or insulin resistance and/or T2DM
• History of DCM/CHF
• Hearing loss
• Hepatic dysfunction
• Renal failure
• Short stature
• Males: hypogonadism
• Females: irregular menses
Note: at least 90% of patients with BBS and 100% of patients with AS must have genetically confirmed diagnosis at the time of enrollment
• A genetically confirmed diagnosis of BBS is defined as a homozygous or compound heterozygous loss-of-function mutation in BBS genes; patients without a genetically confirmed BBS diagnosis must be reviewed with the Sponsor medical monitor prior to enrollment.
• A genetically confirmed diagnosis of AS is defined as a homozygous or compound heterozygous loss-of-function mutation in the ALMS1 gene.
Once 10% of patients without a confirmed BBS diagnosis have been enrolled in the study, sites will be notified that only genetically confirmed BBS patients may be enrolled.
2. b%6 years of age.
3. Obese, defined as BMI b%30 kg/m2 for patients b%16 years of age or weight >97th percentile for age and sex on growth chart assessment for patients 6 to 15 years of age.
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 is 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 follicle stimulating hormone (FSH) level in the post-menopausal lab range), orfailure to have progressed to Tanner Stage V and/or failure to have achieved mena
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. These patients may be reconsidered approximately 1 month after cessation of such intensive regimens.
2. Current or prior (within prior 2 months) use of any medication, including those approved to treat obesity, that could impact the efficacy results of this study (eg, orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion, liraglutide). Patients on a stable dose and regimen (for at least 2 months) of medication to treat attention deficit hyperactivity disorder (ADHD) may be enrolled in the study as long as they agree to remain on the same dose and regimen during the 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, resulted in <10% weight loss compared to pre-operative baseline weight, or there is 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 Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-V) 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. In patients with no significant neurocognitive deficits:
• A PHQ-9 score of b%15 and/or
• Any suicidal ideation of type 4 or 5 on the C-SSRS, any lifetime history of a suicide attempt, or any suicidal behavior in the last month.
6. 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.
7. 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 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 is exclusionary, but the presence of NAFLD is not be exclusionary. 8. Moderate to severe renal dysfunction defined as <30 mL/min (Appendix
11.6).
9. History or close family history (parents or siblings) of skin cancer or melanoma (excluding non-invasive basal or squamous cell lesion), or patient history of ocular-cutaneous albinism.
10. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion), determined as part of comprehensive skin evaluation performed by a qualified dermatologist during screening. Any concerning lesions identified during the screening period will be biopsied and results must be known to be benign prior to enrollment. I
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method