Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study of AG-881 in Subjects With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation
3 other identifiers
interventional
331
11 countries
84
Brief Summary
Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of vorasidenib to placebo in participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment. Participants will be required to have central confirmation of IDH mutation status prior to randomization. Approximately 340 participants are planned to be randomized 1:1 to receive orally administered vorasidenib 40 mg QD or placebo.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2020
Longer than P75 for phase_3
84 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 11, 2019
CompletedFirst Posted
Study publicly available on registry
November 15, 2019
CompletedStudy Start
First participant enrolled
January 5, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 6, 2022
CompletedResults Posted
Study results publicly available
November 24, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2028
ExpectedApril 3, 2025
April 1, 2025
2.7 years
November 11, 2019
September 5, 2023
April 1, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-Free Survival (PFS)
PFS is defined as the time from date of randomization to date of first documented radiographic PD (as assessed by the blinded independent review committee (BIRC) per modified Response Assessment for Neuro-oncology for Low-Grade Gliomas or date of death due to any cause, whichever occurs earlier.
Up to approximately 30 months
Secondary Outcomes (11)
Time to Next Intervention (TTNI)
Up to approximately 3 years
Tumor Growth Rate (TGR)
every 6 months, up to 2 years and 9 months
Objective Response (OR) as Assessed by the Blinded Independent Review Committee (BIRC)
approximatively 30 months
Complete Response (CR) and Partial Response (PR) by BIRC
Approximatively 30 months
Time to Response (TTR) by BIRC
Approximatively 30 months
- +6 more secondary outcomes
Study Arms (2)
Vorasidenib
EXPERIMENTALVorasidenib 40 mg, continuous daily dosing.
Matching Placebo
PLACEBO COMPARATORMatching placebo 40 mg, continuous daily dosing.
Interventions
Eligibility Criteria
You may qualify if:
- Be at least 12 years of age and weigh at least 40 kg.
- Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria.
- Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, gross-total resection), with the most recent surgery having occurred at least 1 year (-1 month) and not more than 5 years (+3 months) before the date of randomization, and no other prior anticancer therapy, including chemotherapy and radiotherapy and not be in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator.
- Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2 (IDH2 R172K/M/W/S/G mutation variants tested) gene mutation status disease by central laboratory testing during the Prescreening period and available 1p19q status by local testing (eg, fluorescence in situ hybridization \[FISH\], comparative genomic hybridization \[CGH\] array, sequencing) using an accredited laboratory.
- Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC.
- Have a Karnofsky Performance Scale (KPS) score (for participants ≥16 years of age) or Lansky Play Performance Scale (LPPS) score (for participants \<16 years of age) of ≥80%.
You may not qualify if:
- Have had any prior anticancer therapy other than surgery (biopsy, sub-total resection, gross-total resection) for treatment of glioma including systemic chemotherapy, radiotherapy, vaccines, small-molecules, IDH inhibitors, investigational agents, laser ablation, etc.
- Have features assessed as high-risk by the Investigator, including brainstem involvement either as primary location or by tumor extension, clinically relevant functional or neurocognitive deficits due to the tumor in the opinion of the Investigator (deficits resulting from surgery are allowed), or uncontrolled seizures (defined as persistent seizures interfering with activities of daily life AND failed 3 lines of antiepileptic drug regimens including at least 1 combination regimen).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (84)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
City of Hope
Duarte, California, 91010, United States
University of California San Diego
La Jolla, California, 92093, United States
UCLA Oncology Center
Los Angeles, California, 90095, United States
University of California Irvine - Hospital
Orange, California, 92868, United States
University of California San Francisco
San Francisco, California, 94143, United States
Stanford Cancer Center
Stanford, California, 94305, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, 80045, United States
Yale University, Yale Cancer Center
New Haven, Connecticut, 06510, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
Sylvester Comprehensive Cancer Center - University of Miami Hospital and Clinics
Miami, Florida, 33136, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago
Chicago, Illinois, 60637, United States
Indiana University Medical Center
Indianapolis, Indiana, 46202, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Maine Medical Partners Neurology
Scarborough, Maine, 04074, United States
John Hopkins Cancer Center
Baltimore, Maryland, 21231, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Metro Minnesota Community Oncology
Minneapolis, Minnesota, 55416, United States
Mayo Comprehensive Cancer
Rochester, Minnesota, 55905, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Tennessee Oncology
Nashville, Tennessee, 37203, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
The University of Utah, Huntsman Cancer Hospital
Salt Lake City, Utah, 84112, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
BC Cancer Agency
Vancouver, British Columbia, V5Z 4E6, Canada
London Health Sciences Centre
London, Ontario, N6A 5W9, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Hospital
Toronto, Ontario, Canada
McGill University Health Center
Montreal, Quebec, H3A 2B4, Canada
Centre Hospitalier Universitaire de Lille
Lille, 59037, France
Hôpital Pierre Wertheimer
Lyon, 69394, France
Hopitaux de La Timone
Marseille, 13385, France
Hospitalier Pitié Salpétrière
Paris, 75013, France
Universitätsklinikum Essen
Essen, 45122, Germany
Universitätsklinikum Hamburg Eppendorf
Hamburg, 20246, Germany
Universitätsklinikum Heidelberg
Heidelberg, 69120, Germany
Klinikum Mannheim Universitätsklinikum
Mannheim, 68135, Germany
Hadassah Medical Center
Jerusalem, 91120, Israel
Rabin Medical Center
Petah Tikva, 49100, Israel
Chaim Sheba Medical Center
Ramat Gan, 52621, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906, Israel
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Turin, Piedmont, 10126, Italy
Ospedale Bellaria
Bologna, 40139, Italy
Istituto Oncologico Veneto - I.R.C.C.S.
Padua, 35128, Italy
Istituto Nazionale Tumori Regina Elena
Roma, 144, Italy
Istituto Clinico Humanitas
Rozzano, 20089, Italy
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8560, Japan
Fujita Health University Hospital
Toyoake, Aichi-ken, 470-1192, Japan
Hiroshima University Hospital
Minami-Ku, Hiroshima, 734-8551, Japan
The University of Tokyo Hospital
Bunkyō-Ku, Tokyo, 113-8655, Japan
National Cancer Center Hospital
Chuo Ku, Tokyo, 104-0045, Japan
Kumamoto University Hospital
Kumamoto, 860-8556, Japan
University Hospital, Kyoto Prefectural University of Medicine
Kyoto, 602-8566, Japan
Kyoto University Hospital
Kyoto, 606-8507, Japan
Okayama University Hospital
Okayama, 700-8558, Japan
Haaglanden MC, Antoniushove
Leidschendam, South Holland, 2262 BA, Netherlands
Erasmus Medical Center
Rotterdam, 3015 GD, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
Hospital Universitario Vall d'Hebrón
Barcelona, 08035, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hôpitaux Universitaire de Genève
Geneva, 1211, Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, 1011, Switzerland
Universitätsspital Zürich
Zurich, 8006, Switzerland
Freeman Hospital
Newcastle upon Tyne, England, NE7 7DN, United Kingdom
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT, United Kingdom
Western General Hospital Edinburgh - PPDS
Edinburgh, EH4 2XY, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Related Publications (2)
Mellinghoff IK, van den Bent MJ, Blumenthal DT, Touat M, Peters KB, Clarke J, Mendez J, Yust-Katz S, Welsh L, Mason WP, Ducray F, Umemura Y, Nabors B, Holdhoff M, Hottinger AF, Arakawa Y, Sepulveda JM, Wick W, Soffietti R, Perry JR, Giglio P, de la Fuente M, Maher EA, Schoenfeld S, Zhao D, Pandya SS, Steelman L, Hassan I, Wen PY, Cloughesy TF; INDIGO Trial Investigators. Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med. 2023 Aug 17;389(7):589-601. doi: 10.1056/NEJMoa2304194. Epub 2023 Jun 4.
PMID: 37272516RESULTCloughesy TF, van den Bent MJ, Touat M, Blumenthal DT, Peters KB, Ellingson BM, Clarke JL, Mendez J, Yust-Katz S, Welsh L, Mason WP, Ducray F, Umemura Y, Nabors B, Holdhoff M, Hottinger AF, Arakawa Y, Sepulveda JM, Wick W, Soffietti R, Perry J, Giglio P, de la Fuente M, Maher E, Bottomley A, Tron AE, Yi D, Zhao D, Pandya SS, Steelman L, Hassan I, Wen PY, Mellinghoff IK; INDIGO trial investigators. Vorasidenib in IDH1-mutant or IDH2-mutant low-grade glioma (INDIGO): secondary and exploratory endpoints from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2025 Dec;26(12):1665-1675. doi: 10.1016/S1470-2045(25)00472-3. Epub 2025 Oct 29.
PMID: 41175888DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Studies Department
- Organization
- Institut de Recherches Internationales Servier (I.R.I.S.)
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 11, 2019
First Posted
November 15, 2019
Study Start
January 5, 2020
Primary Completion
September 6, 2022
Study Completion (Estimated)
May 1, 2028
Last Updated
April 3, 2025
Results First Posted
November 24, 2023
Record last verified: 2025-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- After Marketing Authorisation in EEA or US if the study is used for the approval.
- Access Criteria
- Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.