E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | 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 | |
E.1.1.1 | Medical condition in easily understood language | Obesity caused by rare genetic defects in patients causing extreme hunger. | |
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 | E.1.2 | Level | PT | E.1.2 | Classification code | 10084105 | E.1.2 | Term | Leptin receptor deficiency | E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders | |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 | E.1.2 | Level | PT | E.1.2 | Classification code | 10083937 | E.1.2 | Term | Pro-opiomelanocortin deficiency | E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders | |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 | E.1.2 | Level | LLT | E.1.2 | Classification code | 10048680 | E.1.2 | Term | Bardet-Biedl syndrome | E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders | |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial | To evaluate the effect of setmelanotide on weight in pediatric patients aged 2 to <6 years with obesity due to either (1) biallelic variants of the POMC, PCSK1 or LEPR genes or (2) Bardet-Biedl Syndrome (BBS) by determining if they meet a “responder” definition for change in body weight. | |
E.2.2 | Secondary objectives of the trial | Secondary: To evaluate the effect of setmelanotide on weight in pediatric patients aged 2 to <6 years with obesity due to either (1) biallelic variants of the POMC, PCSK1 or LEPR genes or (2) BBS using additional measures of changes in body weight. To evaluate the safety and tolerability of setmelanotide in pediatric patients aged 2 to <6 years with obesity due to either (1) biallelic variants of the POMC, PCSK1 or LEPR genes or (2) BBS. Exploratory: To evaluate the effect of setmelanotide on (1) metabolic parameters, (2) waist circumference, (3) pharmacokinetics and (4) quality of life and care taker burden in pediatric patients between the ages of 2 to <6 years old with obesity due to either (1) biallelic variants of the POMC, PCSK1 or LEPR genes or (2) BBS. | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | 1. Patients must have obesity due to either: a. POMC, PCSK1, or LEPR deficiency, confirmed by genetic testing demonstrating biallelic variants that are interpreted as pathogenic, likely pathogenic, or of undetermined significance (VUS) by the American College of Medical Genetics and Genomics (ACMG) criteria, or b. BBS as defined by both (1) the Beales Criteria, 1999 (Beales 1999 [Appendix 16.1]) AND (2) genetic confirmation of homozygous or compound heterozygous loss-of-function mutation in BBS genes. 2. Age between 2 to <6 years at the time of informed consent are eligible for the study. 3. Obese, defined as body mass index (BMI) ≥97th percentile for age and gender AND body weight of at least 20 kg at the time of enrollment 4. Parent or guardian of study participant is able to communicate well with the PI, to understand and comply with the requirements of the study (including once daily (QD) injection regimen and all other study procedures) and is able to understand and sign the written consent. | |
E.4 | Principal exclusion criteria | 1. HbA1c >9.0% at screening 2. History of significant liver disease other than non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). 3. Glomerular filtration rate (GFR) <60 mL/min 4. History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism. 5. 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 the PI during screening. Any concerning lesions identified during screening will be biopsied and results known to be benign prior to enrollment. 6. Patient is, in the opinion of the Study PI, not suitable to participate in the study. 7. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing. 8. Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide. 9. Significant hypersensitivity to any excipient in the study drug. 10. Inadequate hepatic function as evidenced by elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) values >5x Upper limit of normal (ULN). | |
E.5 End points |
E.5.1 | Primary end point(s) | The response rate to setmelanotide, with a “responder” defined as a decrease from baseline in the patient’s BMI z-score of ≥0.2. | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | Patient age, height and weight will be recorded at each patient visit starting screening, enrollment, week 2, 4, 6, 8, 12, 16, 20, 28, 36, 44 and 52. | |
E.5.2 | Secondary end point(s) | Secondary: The change in percent of the 95th percentile of body mass index (BMI), the actual and percent change in weight and the change in BMI and change in BMI-z score from baseline to the end of study will be summarized. Frequency and severity of AEs, vital signs, and change from baseline in bone age, Ages & Stages Questionnaires, Third Edition (ASQ®-3) and laboratory evaluations. Exploratory: The change from baseline in metabolic parameters (as measured by the fasting lipid profile and change in hemoglobin A1c), change in waist circumference from baseline, pharmacokinetic parameters, and change in caregiver burden (as measured by the Zarit Burden Interview instrument) and quality of life (as measured by the Work Productivity and Activity Impairment, PROMIS Global Health - Parent Proxy and Caregivers instruments) will be summarized. | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | End points are assessed from baseline to end of treatment. | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 | The trial involves single site in the Member State concerned | Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | Australia | Netherlands | United Kingdom | United States | |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |