ong Term Extension Trial of setmelanotide for patients who havecompleted a trial of Setmelanotide for the treatment of obesity associated with genetic defects

Phase 1

• Conditions: Patients with obesity caused by genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway. Human Genetics studies have identified several diseases that are the result of genetic defects affecting the MC4R pathway, for example:•POMC deficiency obesity due to mutations in the POMC gene•PCSK1 deficiency due to mutations in the PCSK1 gene•LEPR deficiency obesity due to mutations in the LEPR gene•Bardet-Biedl syndrome•Alström syndrome; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2017-005006-35-NL
• Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-04-17
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 109

Inclusion Criteria

1. Patients aged 2 or older (or aged >2 years as per local regulations; only patients aged 12 years or older may be enrolled in the trial in Greece; only patients 6 years or older may be enrolled in the trial in Germany) who have completed participation in a previous setmelanotide clinical trial.

2. If patient received setmelanotide on an open-label basis in a previous setmelanotide clinical trial, patient demonstrated adequate safety and meaningful clinical benefit (efficacy) in the previous setmelanotide trial. Meaningful clinical benefit is defined as follows:
• Patients 18 years of age or younger that have completed participation on active drug and demonstrated adequate safety and at least 3% BMI reduction or reduction in BMI Z-score of 0.2 compared to baseline.
• Patients over 18 years of age should show reduction of 3% BMI compared to baseline. If the patient received trial drug in a double-blind basis in the previous placebo-controlled clinical trial, patient tolerated trial drug in the previous clinical trial.

3. Patient and/or parent or guardian is able to communicate well with the Investigator, to understand and comply with the requirements of the trial, and to understand and sign the written informed consent/assent. The patient must consent/assent to participate in the trial.

4. Patient must meet one of the following requirements regarding contraception:
• If a female of childbearing potential, defined as fertile, following menarche and until becoming post- menopausal unless permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral
oophorectomy), must use a highly effective form of contraception as outlined in Section 6.2.1.
• If a female of non-childbearing potential, defined as permanently sterile (status post hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or post- menopausal for at least 12 months (and confirmed with a screening follicle-stimulating hormone (FSH) level in the post-menopausal laboratory range), contraception is not required during the trial.
• Younger female patients who have not reached menarche upon trial entry will be assessed for Tanner staging and at first menarche will be required to comply with contraception requirements and pregnancy
testing as outlined in the protocol.
• If a male with female partner(s) of childbearing potential, must agree to a double barrier method if they become sexually active during the trial. Furthermore, male patients must not donate sperm during and for 90 days following their participation in the trial.
Are the trial subjects under 18? yes
Number of subjects for this age range: 300
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 101
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

Exclusion Criteria:
1. Pregnant and/or breastfeeding women
2. Significant dermatologic findings relating to melanoma or premelanoma 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 trial.
3. Patient is, in the opinion of the Study Investigator, not suitable to participate in the trial.
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 enrollment in the trial
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 trial 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 (C-SSRS). Any lifetime history of a suicide attempt, or any suicidal behavior since the last visit in the index study
Note: Patients who are unable to complete the PHQ-9 or C-SSRS due to significant neurocognitive defects may be enrolled in the trial, 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. Severe renal dysfunction as defined by a glomerular filtration rate (GFR) <30 mL/min/1.73 m2 in patients >12 years of age (see appendix 11.5).

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 ocularcutaneous albinism.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified