Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2021-002855-12
    Sponsor's Protocol Code Number:RM-493-034
    National Competent Authority:Greece - EOF
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-12-07
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGreece - EOF
    A.2EudraCT number2021-002855-12
    A.3Full title of the trial
    A 2-Stage (Open-Label Followed by Randomized Double-Blind, Placebo-Controlled Stage), Phase 2 Trial of Setmelanotide in Patients with Specific Gene Variants in the Melanocortin-4 Receptor Pathway
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of setmelanotide in patients with obesity with specific genetic defects
    A.3.2Name or abbreviated title of the trial where available
    Setmelanotide in patients with specific gene defects
    A.4.1Sponsor's protocol code numberRM-493-034
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04963231
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation PlanP/215/2021
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorRhythm Pharmaceuticals Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportRhythm Pharmaceuticals Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationRhythm Pharmaceuticals Inc.
    B.5.2Functional name of contact pointClinical Operations
    B.5.3 Address:
    B.5.3.1Street Address222 Berkeley Street, Suite 1200
    B.5.3.2Town/ cityBoston
    B.5.3.3Post codeMA02116
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 857 264 4280
    B.5.5Fax number+1 857 264 4299
    B.5.6E-mailoohayon@rhythmtx.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Imcivree
    D.2.1.1.2Name of the Marketing Authorisation holderRhythm Pharmaceuticals Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/16/1703, EU/3/18/2101
    D.3 Description of the IMP
    D.3.1Product nameSetmelanotide
    D.3.2Product code RM-493
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSetmelanotide
    D.3.9.1CAS number 920014-72-8
    D.3.9.2Current sponsor codeRM-493
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Specific Gene Defects in the Melanocortin-4 Receptor Pathway, responsible for improper functions of certain
    messenger materials in the body. E.g Melanocyte-Stimulating Hormone (MSH)
    E.1.1.1Medical condition in easily understood language
    Improper function of certain messenger materials in the body that control body weight and hunger in people
    E.1.1.2Therapeutic area Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the proportion of patients with obesity with genetic variants in a specific gene in the melanocortin-4 receptor (MC4R) pathway who achieve a clinically meaningful reduction in body weight in response to setmelanotide at the end of open-label treatment
    E.2.2Secondary objectives of the trial
    To evaluate change in weight parameters and hunger in response to setmelanotide in patients with genetic variants in a specific gene in the MC4R pathway at the end of open-label treatment
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patients must have a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity.
    Note: Genetic testing requirements and a list of genes which have variants that are eligible for enrollment into the trial are provided in Appendix 1.
    2. Patients between the ages of 6 and 65, inclusive, at the time of signing Informed Consent or Assent.
    3. Patients with obesity, defined as BMI ≥40 kg/m2 for patients ≥18 years of age or BMI ≥97th percentile for age and gender for patients 6 to <18 years of age based on the United States (US) Centers for Disease Control and Prevention criteria.
    4. Patient and/or parent or guardian is able to communicate well with the Investigator, to understand and comply with the requirements of the trial (including the once daily [QD] injection regimen and all other trial procedures) and is able to understand and sign the written informed consent/assent. Patients who are unable to comply with all trial procedures due to cognitive limitations or any other reason should not be enrolled.
    5. Patient must meet one of the following requirements:
    Female participants of childbearing potential, defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), must be confirmed non-pregnant and agree to use a highly effective form of contraception throughout the trial and for 90 days following the trial.
    Highly effective forms of contraception are detailed below and in Section 8.9.7:
    • Combined (estrogen and progestin) hormonal contraception associated with inhibition of ovulation (i.e., oral, intravaginal, or transdermal)
    • Progestin-only hormonal contraception associated with inhibition of ovulation (oral, implantable, or injectable)
    • Intrauterine device (IUD)
    • Intrauterine hormone-releasing system
    • Bilateral tubal occlusion
    • Vasectomy/vasectomized partner (provided that the vasectomized partner is the sole sexual partner of the female participant, and the vasectomized partner has received medical assessment of surgical success)
    • Sexual abstinence, only if it is the preferred and usual lifestyle of the patient
    Female participants 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 level in the post-menopausal lab range) and do not require contraception during the trial.
    Younger female patients who have not achieved sexual maturity at trial entry will be assessed for Tanner staging and required to comply with contraception requirements at first menarche.
    Male participants with female partners of childbearing potential must agree to use a highly effective method contraception if they become sexually active during the trial or within 90 days following their participation in the trial. Male patients must also not donate sperm during and for 90 days following their participation in the trial.
    6. Symptoms or behaviors of hyperphagia persistent during the patient’s life, including manifestations in childhood, as determined by the Investigator at screening.
    E.4Principal exclusion criteria
    1. Patients with the following genetic variants: biallelic Bardet-Biedl Syndrome (BBS); biallelic Alström Syndrome 1 (ALMS1); homozygous, heterozygous, or compound heterozygous variants in MC4R, pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), leptin receptor (LEPR), nuclear receptor coactivator 1 (NCOA1; steroid receptor coactivator-1 [SRC1]) or SRC homology 2 B adapter protein 1 (SH2B1) genes as well as 16p11.2 chromosomal deletions that include the SH2B1 gene.
    2. Weight loss >2% in the previous 3 months.
    Patients will not be excluded for using regimens for weight maintenance or to prevent weight gain, such as dietary and/or exercise regimens, or medications, supplements or herbal treatments (e.g., orlistat, lorcaserin, phentermine, topiramate, naltrexone, bupropion, glucagon-like peptide-1 [GLP-1] receptor agonists, etc.), provided:
    • the regimen and/or dose has been stable for at least 3 months prior to randomization
    • the patient has not experienced weight loss >2% during the previous 3 months, AND
    • the patient intends to keep the regimen and/or dose stable throughout the course of the trial.
    3. Bariatric surgery or procedure (e.g., gastric bypass/band/sleeve, duodenal switch, gastric balloon, intestinal barrier, etc.) within the last 6 months. All patients with a history of bariatric surgery or procedures must be discussed with, and receive approval from, the Sponsor prior to enrollment.
    4. Documented diagnosis of current unstable major psychiatric disorder(s) (e.g., major depressive disorder, bipolar disorder, schizophrenia, etc.) or documented worsening psychiatric condition that required changes in treatment regimen within the previous 2 years, or other psychiatric related risks that the Investigator believes may interfere with trial compliance or patient safety.
    5. Clinically significant depression or suicidality, as defined by: any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) during Screening, any suicide attempt during the patient’s lifetime, any suicidal behavior in the last month, or a Patient Health Questionnaire-9 (PHQ-9) score of ≥15 during Screening process.
    Note: Patients who are unable to complete the PHQ-9 or C-SSRS due to significant neurocognitive impairment may be enrolled in the trial provided that there are no clinical signs or symptoms of significant depression or suicidal behavior in the opinion of the Investigator.
    6. Current, clinically significant pulmonary, cardiac, endocrine/metabolic, hepatic, or oncologic disease considered severe enough to interfere with the trial and/or confound the results. Any patient with a potentially clinically significant disease should be reviewed with the Sponsor to determine eligibility.
    7. Significant features of, or meeting the diagnostic criteria for, a genetic syndrome that is associated with obesity.
    Note: Although some of the genetic variants that are eligible to be enrolled into this trial are associated with specific syndromes, the intent of this trial is not to enroll children with significant cognitive impairment or other significant co-morbidities. Patients with eligible genetic variants, but who otherwise do not exhibit the syndrome, are eligible for enrollment.
    8. Glycated hemoglobin (HbA1C) >10.0% at Screening.
    9. History of significant liver disease other than non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). Patients with NAFLD or NASH will not be excluded based on this criterion
    10. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 at Screening. In patients ≥18 years of age the Modification of Diet in Renal Disease (MDRD) Equation should be used to calculate eGFR. In patients <18 years of age, the Bedside Schwartz Equation should be used for calculation of GFR.
    11. History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism.
    Note: If the type of skin cancer in patient’s or close family history is not known, then the patient should not be enrolled into the trial.
    12. 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 Investigator during Screening. If any concerning lesions are identified during Screening, the patient should be referred to a dermatologist. Any concerning lesions identified during Screening 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.
    13. Patient is, in the opinion of the Investigator, not suitable to participate in the trial.
    14. Participation in any clinical trial with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first day of dosing.
    E.5 End points
    E.5.1Primary end point(s)
    The proportion of patients by genotype who demonstrate a significant clinically meaningful response (defined below) to setmelanotide at the end of Stage 1:
    − For all patients: achieving a ≥5% reduction in BMI from Baseline
    E.5.1.1Timepoint(s) of evaluation of this end point
    16 weeks
    E.5.2Secondary end point(s)
    • Mean change and percent change in BMI from Baseline to end of Stage 1 in all patients and patients ≥18 years old, per gene
    • Mean change and percent change in body weight from Baseline to end of Stage 1 in patients ≥18 years old, per gene
    • Mean change in BMI Z-score from Baseline to end of Stage 1 in patients <18 years old, per gene
    • Mean percent change in the weekly average of the daily maximal hunger score from Baseline to end of Stage 1 in patients ≥12 years old, per gene
    • The proportion of patients ≥12 years old, per gene, who achieve a ≥2-point reduction (improvement) from Baseline to end of Stage 1 in the weekly average of the daily maximal hunger score.
    E.5.2.1Timepoint(s) of evaluation of this end point
    16 weeks
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA14
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Germany
    Greece
    Israel
    Netherlands
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 50
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 19
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 30
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 115
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    minors
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 48
    F.4.2.2In the whole clinical trial 165
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patients who respond to setmelanotide may be offered the option of enrolling into a Long-Term Extension study
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-02-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-03-17
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 17:29:54 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA