<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03032172</url>
  </required_header>
  <id_info>
    <org_study_id>BP39054</org_study_id>
    <secondary_id>2016-004184-39</secondary_id>
    <nct_id>NCT03032172</nct_id>
  </id_info>
  <brief_title>A Study of Risdiplam (RO7034067) in Adult and Pediatric Participants With Spinal Muscular Atrophy</brief_title>
  <acronym>Jewelfish</acronym>
  <official_title>An Open-Label Study to Investigate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Risdiplam (RO7034067) in Adult and Pediatric Patients With Spinal Muscular Atrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, exploratory, non-comparative, and open-label study to investigate the&#xD;
      safety, tolerability, PK, and PK/PD relationship of risdiplam in adults, children and infants&#xD;
      with Spinal Muscular Atrophy (SMA) previously enrolled in Study BP29420 (Moonfish) with the&#xD;
      splicing modifier RO6885247 or previously treated with nusinersen, olesoxime or AVXS-101.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 3, 2017</start_date>
  <completion_date type="Anticipated">December 27, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 27, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Scale, V 4.0</measure>
    <time_frame>Baseline up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Emergence or Worsening of Symptoms As Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) (Adult Version for Adults and Adolescents, Pediatric Version for Patients Aged 6-11 Years)</measure>
    <time_frame>Baseline up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Protocol Defined Clinically Significant Changes in Ophthalmological Assessments</measure>
    <time_frame>Baseline up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Protocol Defined Clinically Significant Changes in Neurological Assessments</measure>
    <time_frame>Baseline up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tanner Staging Among all Participants Aged From 9 to 17 Years</measure>
    <time_frame>Baseline up to 5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Plasma Concentration of Risdiplam</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Risdiplam</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration Versus Curve (AUC) of Risdiplam</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Concentration of Risdiplam at the End of Dosing Interval (Ctrough)</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Plasma Concentration of Risdiplam Metabolite</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of Risdiplam Metabolite</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC of Risdiplam Metabolite</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Ctrough of Risdiplam Metabolite</measure>
    <time_frame>Up to 2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>SMN messenger Ribonucleic Acid (mRNA) Level in Blood</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SMN Protein Levels in Blood</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">174</enrollment>
  <condition>Spinal Muscular Atrophy</condition>
  <arm_group>
    <arm_group_label>Risdiplam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive multiple doses of risdiplam orally once daily for 24 months. After 24-month treatment, participants will be offered the opportunity to enter the open-label extension (OLE) phase.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Risdiplam</intervention_name>
    <description>Risdiplam will be administered orally once daily.</description>
    <arm_group_label>Risdiplam</arm_group_label>
    <other_name>RO7034067</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of 5q-autosomal recessive SMA&#xD;
&#xD;
          -  Previous enrollment in Study BP29420 (Moonfish) with the splicing modifier RO6885247&#xD;
             or previous treatment with any of the following: 1.) Nusinersen (defined as having&#xD;
             received &gt;= 4 doses of nusinersen, provided that the last dose was received &gt;= 90 days&#xD;
             prior to screening) or 2.) Olesoxime (provided that the last dose was received &lt;= 12&#xD;
             months and &gt;= 90 days prior to screening) or 3.) AVXS-101 (provided that the time of&#xD;
             treatment was &gt;= 12 months prior to screening)&#xD;
&#xD;
          -  Adequately recovered from any acute illness at the time of screening and considered&#xD;
             well enough to participate in the opinion of the Investigator&#xD;
&#xD;
          -  For women of childbearing potential: negative blood pregnancy test at screening,&#xD;
             agreement to remain abstinent (refrain from heterosexual intercourse) or use&#xD;
             contraceptive measures, and agreement to refrain from donating eggs for at least 28&#xD;
             days after the final dose of study drug&#xD;
&#xD;
          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use&#xD;
             contraceptive measures and agreement to refrain from donating sperm&#xD;
&#xD;
          -  For participants aged 2 years or younger at screening: 1.) Parent or caregiver of&#xD;
             participant is willing to consider nasogastric, naso-jejunal or gastrostomy tube&#xD;
             placement, as recommended by the Investigator, during the study to maintain safe&#xD;
             hydration, nutrition and treatment delivery; 2.) Parent or caregiver of participant is&#xD;
             willing to consider the use of non-invasive ventilation, as recommended by the&#xD;
             Investigator during the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to meet study requirements&#xD;
&#xD;
          -  Concomitant participation in any investigational drug or device study&#xD;
&#xD;
          -  With the exception of studies of olesoxime, AVXS-101, or nusinersen: Previous&#xD;
             participation in any investigational drug or device study within 90 days prior to&#xD;
             screening, or 5 half-lives of the drug, whichever is longer&#xD;
&#xD;
          -  Any history of gene or cell therapy, with the exception of AVXS-101&#xD;
&#xD;
          -  Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system&#xD;
             diseases as considered to be clinically significant by the Investigator&#xD;
&#xD;
          -  Inadequate venous or capillary blood access for the study procedures, in the opinion&#xD;
             of the Investigator&#xD;
&#xD;
          -  For patients aged &lt; 2 years, hospitalization for a pulmonary event within 2 months&#xD;
             prior to screening and pulmonary function not fully recovered at the time of screening&#xD;
&#xD;
          -  Lactating women&#xD;
&#xD;
          -  Suspicion of regular consumption of drugs of abuse&#xD;
&#xD;
          -  For adults and adolescents only, positive urine test for drugs of abuse or alcohol at&#xD;
             screening or Day -1 visit&#xD;
&#xD;
          -  Presence of clinically significant electrocardiogram (ECG) abnormalities before study&#xD;
             drug administration from average of triplicate measurement or cardiovascular disease&#xD;
&#xD;
          -  History of malignancy if not considered cured&#xD;
&#xD;
          -  For participants aged &gt; 6 years, significant risk for suicidal behavior, in the&#xD;
             opinion of the Investigator as assessed by the Columbia-Suicide Severity Rating Scale&#xD;
             (C-SSRS)&#xD;
&#xD;
          -  Any major illness within one month before the screening examination or any febrile&#xD;
             illness within one week prior to screening and up to first dose administration&#xD;
&#xD;
          -  Recently initiated treatment for spinal muscular atrophy (within &lt;6 weeks prior to&#xD;
             enrollment) with oral salbutamol or another beta 2-adrenergic agonist taken orally&#xD;
&#xD;
          -  Any prior use of chloroquine, hydroxychloroquine, retigabin, vigabatrin or&#xD;
             thioridazine, is not allowed&#xD;
&#xD;
          -  Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to risdiplam&#xD;
             or to the constituents of its formulation&#xD;
&#xD;
          -  Concomitant disease or condition that could interfere with, or treatment of which&#xD;
             might interfere with, the conduct of the study, or that would, in the opinion of the&#xD;
             Investigator, pose an unacceptable risk to the participant in this study&#xD;
&#xD;
          -  Recent history (less than one year) of ophthalmological diseases&#xD;
&#xD;
          -  Any prior use of an inhibitor or inducer of FMO1 or FMO3 taken within 2 weeks (or&#xD;
             within 5 elimination half-lives, whichever is longer) prior to dosing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemours Children's Hospital</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32827</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Childrens Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center; The Neurological Institute of New York</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Femme Mere Enfant; Medecine Physique et Readaptation Pediatrique ? L?ESCALE</name>
      <address>
        <city>Bron</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Roger Salengro</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU de Montpellier, Hopital Gui de Chauliac; Service de Neuropediatrie</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Necker-Enfants Malades; Service de neuropédiatrie</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital des Enfants; Unite de Neurologie Pediatrique</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Essen; Klinik für Kinderheilkunde I</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Freiburg; Klinik für Neuropädiatrie und Muskelerkrankungen</name>
      <address>
        <city>Freiburg</city>
        <zip>79106</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Ospedale Pediatrico Bambino Gesù; U.O. Malattie Neuromuscolari e Neurodegenerative</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00165</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Agostino Gemelli; Dipartimento di Neuropsichiatria Infantile</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto Giannina Gaslini; U.O.S.D. Centro di Miologia e Patologie Neurodegenerative</name>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16147</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Unità Operativa Complessa di Neurologia</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UOSD Malattie Neurodegenerative</name>
      <address>
        <city>Messina</city>
        <state>Sicilia</state>
        <zip>98125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMC Utrecht; Polkliniek Neuromusculaire ziekten</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie</name>
      <address>
        <city>Warszawa</city>
        <zip>02-097</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitäts-Kinderspital (UKBB) Neuropädiatrie</name>
      <address>
        <city>Basel</city>
        <zip>4005</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Birmingham Heartlands Hospital</name>
      <address>
        <city>Birmingham</city>
        <zip>B9 5SS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCL Institute of Child Health &amp; Great Ormond Street Hospital for Children</name>
      <address>
        <city>London</city>
        <zip>WC1N 1EH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Newcastle upon Tyne Hospitals NHS Foundation Trust</name>
      <address>
        <city>Newcastle upon Tyne</city>
        <zip>NE7 7DN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Switzerland</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://roche-sma-clinicaltrials.com</url>
    <description>roche-sma-clinicaltrials.com provides information about the Roche Jewelfish clinical trial NCT03032172 and molecule being investigated in SMA.</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>July 19, 2023</last_update_submitted>
  <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Atrophy</mesh_term>
    <mesh_term>Muscular Atrophy, Spinal</mesh_term>
    <mesh_term>Atrophy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Risdiplam</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03032172
org study id: BP39054
secondary id: 2016-004184-39
nct id: NCT03032172
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a multi-center, exploratory, non-comparative, and open-label study to investigate the
      safety, tolerability, PK, and PK/PD relationship of risdiplam in adults, children and infants
      with Spinal Muscular Atrophy (SMA) previously enrolled in Study BP29420 (Moonfish) with the
      splicing modifier RO6885247 or previously treated with nusinersen, olesoxime or AVXS-101.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Scale, V 4.0
time frame: Baseline up to 5 years
measure: Percentage of Participants With Emergence or Worsening of Symptoms As Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) (Adult Version for Adults and Adolescents, Pediatric Version for Patients Aged 6-11 Years)
time frame: Baseline up to 5 years
measure: Percentage of Participants With Protocol Defined Clinically Significant Changes in Ophthalmological Assessments
time frame: Baseline up to 5 years
measure: Percentage of Participants With Protocol Defined Clinically Significant Changes in Neurological Assessments
time frame: Baseline up to 5 years
measure: Tanner Staging Among all Participants Aged From 9 to 17 Years
time frame: Baseline up to 5 years
measure: Mean Plasma Concentration of Risdiplam
time frame: Up to 2 years
measure: Maximum Plasma Concentration (Cmax) of Risdiplam
time frame: Up to 2 years
measure: Area Under the Plasma Concentration Versus Curve (AUC) of Risdiplam
time frame: Up to 2 years
measure: Concentration of Risdiplam at the End of Dosing Interval (Ctrough)
time frame: Up to 2 years
measure: Mean Plasma Concentration of Risdiplam Metabolite
time frame: Up to 2 years
measure: Cmax of Risdiplam Metabolite
time frame: Up to 2 years
measure: AUC of Risdiplam Metabolite
time frame: Up to 2 years
measure: Ctrough of Risdiplam Metabolite
time frame: Up to 2 years
measure: SMN messenger Ribonucleic Acid (mRNA) Level in Blood
time frame: Up to 2 years
measure: SMN Protein Levels in Blood
time frame: Up to 2 years
arm group label: Risdiplam
arm group type: Experimental
description: Participants will receive multiple doses of risdiplam orally once daily for 24 months. After 24-month treatment, participants will be offered the opportunity to enter the open-label extension (OLE) phase.
intervention type: Drug
intervention name: Risdiplam
description: Risdiplam will be administered orally once daily.
arm group label: Risdiplam
other name: RO7034067
criteria: 
gender: All
minimum age: 6 Months
maximum age: 60 Years
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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facility: 
country: Belgium
country: France
country: Germany
country: Italy
country: Netherlands
country: Poland
country: Switzerland
country: United Kingdom
country: United States
url: http://roche-sma-clinicaltrials.com
description: roche-sma-clinicaltrials.com provides information about the Roche Jewelfish clinical trial NCT03032172 and molecule being investigated in SMA.
responsible party type: Sponsor
mesh term: Muscular Atrophy
mesh term: Muscular Atrophy, Spinal
mesh term: Atrophy
mesh term: Risdiplam
sharing ipd: Yes
ipd description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).