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

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ClinicalTrials.gov Identifier: NCT04164901

Recruitment Status : Active, not recruiting

First Posted : November 15, 2019

Last Update Posted : May 17, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Servier ( Institut de Recherches Internationales Servier )

Tracking Information

First Submitted Date ^ICMJE

November 11, 2019

First Posted Date ^ICMJE

November 15, 2019

Last Update Posted Date

May 17, 2022

Actual Study Start Date ^ICMJE

January 5, 2020

Estimated Primary Completion Date

October 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Progression-Free Survival (PFS) [ Time Frame: Up to approximately 30 months ]

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

Time to Next Intervention [ Time Frame: Up to approximately 5 years ]
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 30 months ]
Tumor Growth Rate as Assessed by Volume per the Blinded Independent Review Committee (BIRC) [ Time Frame: Up to approximately 30 months ]
Objective Response as Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
Complete Response (CR) + Partial Response (PR) with Response Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
Time to Response with Response Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
Time to CR + PR with Response Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
Duration of Response with Response Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
Duration of CR + PR with Response Assessed per the BIRC and Investigator [ Time Frame: Up to approximately 30 months ]
Overall Survival [ Time Frame: Up to approximately 5 years ]
Health-Related Quality of Life as Measured by Functional Assessment of Cancer Therapy-Brain Questionnaire (FACT-Br) [ Time Frame: Up to approximately 30 months ]
The FACT-Br is a participant-reported measure designed to assess the quality of life for participants with brain tumors. The FACT-Br is a measure comprising the following subscales: Physical Well-Being, Functional Well-Being, Emotional Well-Being, and Social Well-Being subscales from the FACT-G, with the addition of a brain tumor- specific subscale.
Progression-Free Survival (PFS) as Assessed by the Investigator [ Time Frame: Up to approximately 30 months ]
Pharmacokinetics: Plasma Concentrations of Vorasidenib Collected at Specified Time Points [ Time Frame: Days 1 and 15 of Cycle 1(predose and multiple timepoints up to 4 hours postdose), Day 1 of Cycle 2(predose and multiple time points up to 4 hours postdose), Predose on Day 1 of every cycle thereafter(each cycle is 28 days), and within 7 days of last dose ]
Pharmacokinetics: Plasma Concentrations of Metabolite, AGI-69460, Collected at Specified Time Points [ Time Frame: Days 1 and 15 of Cycle 1(predose and multiple timepoints up to 4 hours postdose), Day 1 of Cycle 2(predose and multiple time points up to 4 hours postdose), Predose on Day 1 of every cycle thereafter(each cycle is 28 days), and within 7 days of last dose ]

Original Secondary Outcome Measures ^ICMJE

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to approximately 30 months ]
Tumor Growth Rate as Assessed by Volume [ Time Frame: Up to approximately 30 months ]
Time to Next Intervention [ Time Frame: Up to approximately 5 years ]
Objective Response Rate [ Time Frame: Up to approximately 30 months ]
Time to Response [ Time Frame: Up to approximately 30 months ]
Duration of Response [ Time Frame: Up to approximately 30 months ]
Overall Survival [ Time Frame: Up to approximately 5 years ]
Health-Related Quality of Life as Measured by Functional Assessment of Cancer Therapy-Brain Questionnaire (FACT-Br) [ Time Frame: Up to approximately 30 months ]
The FACT-Br is a participant-reported measure designed to assess the quality of life for participants with brain tumors. The FACT-Br is a measure comprising the following subscales: Physical Well-Being, Functional Well-Being, Emotional Well-Being, and Social Well-Being subscales from the FACT-G, with the addition of a brain tumor- specific subscale.
Progression-Free Survival (PFS) as Assessed by the Investigator [ Time Frame: Up to approximately 30 months ]
Maximum Observed Serum Concentration (Cmax) of AG-881 [ Time Frame: Days 1 and 15 of Cycle 1(predose and multiple timepoints up to 4 hours postdose), Day 1 of Cycle 2(predose and multiple time points up to 4 hours postdose), Predose on Day 1 of every cycle thereafter(each cycle is 28 days), and within 7 days of last dose ]
Area Under Concentration Time Curve from Time 0 to Tau (AUC0-tau) of AG-881 [ Time Frame: Days 1 and 15 of Cycle 1(predose and multiple timepoints up to 4 hours postdose), Day 1 of Cycle 2(predose and multiple time points up to 4 hours postdose), Predose on Day 1 of every cycle thereafter(each cycle is 28 days), and within 7 days of last dose ]
Time to Reach Maximum Serum Concentration (Tmax) of AG-881 [ Time Frame: Days 1 and 15 of Cycle 1(predose and multiple timepoints up to 4 hours postdose), Day 1 of Cycle 2(predose and multiple time points up to 4 hours postdose), Predose on Day 1 of every cycle thereafter(each cycle is 28 days), and within 7 days of last dose ]

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants randomized in a 1:1 allocation (vorasidenib vs Placebo)

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

Grade 2 Glioma
Residual Glioma
Recurrent Glioma

Intervention ^ICMJE

Drug: Vorasidenib
Vorasidenib oral film-coated tablets

Other Name: AG-881
Drug: Matching Placebo
Matching Placebo oral tablets

Study Arms ^ICMJE

Experimental: Vorasidenib
Vorasidenib 40 mg, continuous daily dosing.

Intervention: Drug: Vorasidenib
Placebo Comparator: Matching Placebo
Matching placebo 40 mg, continuous daily dosing. Participants who experience centrally-confirmed radiographic disease progression and who were receiving placebo will have the option to cross-over to vorasidenib, provided certain criteria are met.

Intervention: Drug: Matching Placebo

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Estimated Enrollment ^ICMJE

340

Original Estimated Enrollment ^ICMJE

366

Estimated Study Completion Date ^ICMJE

August 2027

Estimated Primary Completion Date

October 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Key Inclusion Criteria:

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%.

Key Exclusion Criteria:

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).

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

12 Years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Canada, France, Germany, Israel, Italy, Netherlands, Spain, Switzerland, United Kingdom, United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04164901

Other Study ID Numbers ^ICMJE

AG881-C-004
2019-002481-13 ( EudraCT Number )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	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.
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
Supporting Materials:	Informed Consent Form (ICF)
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.
URL:	https://clinicaltrials.servier.com/