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Grade 2 GliomaPhase 3NCT04164901

Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)

A Phase 3 study testing Vorasidenib in people with Grade 2 Glioma and Residual Glioma, run by Institut de Recherches Internationales Servier at 84 sites in 11 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Grade 2 Glioma, Residual Glioma, Recurrent Glioma
What is being tested?
Vorasidenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
331 participants
Where
84 sitesin 11 countries
Study dates
5 Jan 2020to May 2028
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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%.

Who cannot join

  • 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).

Trial locations and contacts

84 sites in 11 countries.

84 sites in 11 countries

United States40 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Colorado Hospital - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • John Hopkins Cancer Center

    Baltimore, Maryland, 21231

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago

    Chicago, Illinois, 60637

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • City of Hope

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University Medical Center

    Indianapolis, Indiana, 46202

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • University of California San Diego

    La Jolla, California, 92093

  • University of Kentucky

    Lexington, Kentucky, 40536

  • UCLA Oncology Center

    Los Angeles, California, 90095

  • Sylvester Comprehensive Cancer Center - University of Miami Hospital and Clinics

    Miami, Florida, 33136

  • Metro Minnesota Community Oncology

    Minneapolis, Minnesota, 55416

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Yale University, Yale Cancer Center

    New Haven, Connecticut, 06510

  • Columbia University Medical Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of California Irvine - Hospital

    Orange, California, 92868

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • University of Pittsburgh Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Mayo Comprehensive Cancer

    Rochester, Minnesota, 55905

  • The University of Utah, Huntsman Cancer Hospital

    Salt Lake City, Utah, 84112

  • University of California San Francisco

    San Francisco, California, 94143

  • Maine Medical Partners Neurology

    Scarborough, Maine, 04074

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford Cancer Center

    Stanford, California, 94305

Other trials in United States

Japan9 sites

  • The University of Tokyo Hospital

    Bunkyō-Ku, Tokyo, 113-8655

  • National Cancer Center Hospital

    Chuo Ku, Tokyo, 104-0045

  • Kumamoto University Hospital

    Kumamoto, 860-8556

  • University Hospital, Kyoto Prefectural University of Medicine

    Kyoto, 602-8566

  • Kyoto University Hospital

    Kyoto, 606-8507

  • Hiroshima University Hospital

    Minami-Ku, Hiroshima, 734-8551

  • Nagoya University Hospital

    Nagoya, Aichi-ken, 466-8560

  • Okayama University Hospital

    Okayama, 700-8558

  • Fujita Health University Hospital

    Toyoake, Aichi-ken, 470-1192

Other trials in Japan

Canada5 sites

  • London Health Sciences Centre

    London, Ontario, N6A 5W9

  • McGill University Health Center

    Montreal, Quebec, H3A 2B4

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • Princess Margaret Hospital

    Toronto, Ontario

  • BC Cancer Agency

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Italy5 sites

  • Ospedale Bellaria

    Bologna, 40139

  • Istituto Oncologico Veneto - I.R.C.C.S.

    Padua, 35128

  • Istituto Nazionale Tumori Regina Elena

    Roma, 144

  • Istituto Clinico Humanitas

    Rozzano, 20089

  • Azienda Ospedaliera Città della Salute e della Scienza di Torino

    Turin, Piedmont, 10126

Other trials in Italy

France4 sites

  • Centre Hospitalier Universitaire de Lille

    Lille, 59037

  • Hôpital Pierre Wertheimer

    Lyon, 69394

  • Hopitaux de La Timone

    Marseille, 13385

  • Hospitalier Pitié Salpétrière

    Paris, 75013

Other trials in France

Germany4 sites

  • Universitätsklinikum Essen

    Essen, 45122

  • Universitätsklinikum Hamburg Eppendorf

    Hamburg, 20246

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • Klinikum Mannheim Universitätsklinikum

    Mannheim, 68135

Other trials in Germany

Israel4 sites

  • Hadassah Medical Center

    Jerusalem, 91120

  • Rabin Medical Center

    Petah Tikva, 49100

  • Chaim Sheba Medical Center

    Ramat Gan, 52621

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 6423906

Other trials in Israel

United Kingdom4 sites

  • Western General Hospital Edinburgh - PPDS

    Edinburgh, EH4 2XY

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • Freeman Hospital

    Newcastle upon Tyne, England, NE7 7DN

  • The Royal Marsden NHS Foundation Trust

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Netherlands3 sites

  • Haaglanden MC, Antoniushove

    Leidschendam, South Holland, 2262 BA

  • Erasmus Medical Center

    Rotterdam, 3015 GD

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

Spain3 sites

  • Hospital Universitario Vall d'Hebrón

    Barcelona, 08035

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

Other trials in Spain

Switzerland3 sites

  • Hôpitaux Universitaire de Genève

    Geneva, 1211

  • Centre Hospitalier Universitaire Vaudois

    Lausanne, 1011

  • Universitätsspital Zürich

    Zurich, 8006

Other trials in Switzerland

About this study

Official title: 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

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.

Being tested
Vorasidenib, Matching Placebo
Keywords
AG-881
Medical subject headings
Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VorasidenibDrug

    Also called AG-881

    Vorasidenib oral film-coated tablets

  • Matching PlaceboDrug

    Matching Placebo oral tablets

Study groups in NCT04164901
Study groupRoleWhat they receive
VorasidenibExperimentalVorasidenib 40 mg, continuous daily dosing.
Receives: Drug: Vorasidenib
Matching PlaceboPlacebo comparatorMatching placebo 40 mg, continuous daily dosing.
Receives: Drug: Matching Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to approximately 30 months

Secondary outcomes (11)

  1. Time to Next Intervention (TTNI)

    TTNI is defined as the time from randomization to the initiation of the first subsequent anticancer therapy (including vorasidenib, for subjects randomized to placebo who subsequently cross over) or death due to any cause.

    Measured: Up to approximately 3 years

  2. Tumor Growth Rate (TGR)

    Calculated as the mean of the percentage change in tumor volume every 6 months

    Measured: every 6 months, up to 2 years and 9 months

  3. Objective Response (OR) as Assessed by the Blinded Independent Review Committee (BIRC)

    OR is defined as a best overall response (BOR) of Complete Response, Partial Rresponse, or minor Response as assessed by the BIRC per the modified Response Assessment in Neuro-oncology for Low-grade Gliomas (RANO-LGG).

    Measured: approximatively 30 months

  4. Complete Response (CR) and Partial Response (PR) by BIRC

    CR and PR is defined as a BOR of CR or PR as assessed by BIRC per the modified RANO-LGG

    Measured: Approximatively 30 months

  5. Time to Response (TTR) by BIRC

    TTR is defined as the time from the date of randomization to the date of first documented CR, PR, or mR by BIRC per the modified RANO-LGG

    Measured: Approximatively 30 months

  6. Time to CR+PR by BIRC

    Time to CR+PR is defined as defined as the time from the date of randomization to the date of first documented CR or PR for subjects with CR or PR per the modified RANO-LGG (by BIRC)

    Measured: Approximatively 30 months

  7. Duration of Response (DoR)

    DoR is defined as the time from the date of first documented CR, PR, or mR to the date of death due to any cause or date of first documented radiographic Prgressive Disease, whichever occurred earlier

    Measured: Approximatively 30 months

  8. Duration of CR+PR

    Duration of CR+PR is defined as the time from the date of first documented CR or PR to the date of death due to any cause or first documented radiographic PD, whichever occurred earlier

    Measured: Approximatively 30 months

  9. Overall Survival (OS)

    OS wad defined as the time from the date of randomization to the date of death due to any cause or data cutoff.

    Measured: Approximatively 30 months

  10. Progression-Free Survival (PFS) by the Investigator

    PFS as assessed by the Investigator per the modified RANO-LGG

    Measured: Approximatively 30 months

  11. Health-Related Quality of Life (FACT-Br)

    Health-Related Quality of Life (HRQoL) Functional Assessment of Cancer Therapy-Brain (FACT-Br) is a 50-item measure comprising the following subscales: Physical Well-Being, Functional Well-Being, Emotional Well-Being, and Social Well-Being subscales from the FACT-General (FACT-G), with the addition of a 23-item brain tumor-specific subscale. These subscales are summed to provide a total score. The total score is given at the end of treatment and total scores range from 0 to 200. Higher scores indicate a better HRQoL

    Measured: Approximatively 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Nov 2019
  2. Study start5 Jan 2020
  3. Primary completion6 Sep 2022
  4. Study completionMay 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants randomized in a 1:1 allocation (vorasidenib vs Placebo)
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
331 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04164901
Sponsor's protocol ID
AG881-C-004
Other IDs
2019-002481-13, 2024-512961-15-00, 2019
Status last verified
Apr 2025
First submitted
11 Nov 2019
Last updated
3 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 37272516

  • Cloughesy 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.

    PubMed 41175888

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Vorasidenib in people with Grade 2 Glioma and Residual Glioma, run by Institut de Recherches Internationales Servier at 84 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 3 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 84 sites in United States, Japan, Canada, Italy, France and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: Up to approximately 30 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04164901, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2025.

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