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 |
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Recruitment Status :
Active, not recruiting
First Posted : November 15, 2019
Last Update Posted : May 17, 2022
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Sponsor:
Institut de Recherches Internationales Servier
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Grade 2 Glioma Residual Glioma Recurrent Glioma | Drug: Vorasidenib Drug: Matching Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 340 participants |
| 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 |
| 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 |
| Actual Study Start Date : | January 5, 2020 |
| Estimated Primary Completion Date : | October 2024 |
| Estimated Study Completion Date : | August 2027 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Vorasidenib
Vorasidenib 40 mg, continuous daily dosing.
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Drug: Vorasidenib
Vorasidenib oral film-coated tablets
Other Name: AG-881 |
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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.
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Drug: Matching Placebo
Matching Placebo oral tablets |
Primary Outcome Measures :
- Progression-Free Survival (PFS) [ Time Frame: Up to approximately 30 months ]
Secondary Outcome Measures :
- 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 ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 12 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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).
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04164901
Locations
Show 77 study locations
Sponsors and Collaborators
Institut de Recherches Internationales Servier
Study Data/Documents:
Individual Participant Data Set
| Responsible Party: | Institut de Recherches Internationales Servier |
| ClinicalTrials.gov Identifier: | NCT04164901 |
| Other Study ID Numbers: |
AG881-C-004 2019-002481-13 ( EudraCT Number ) |
| First Posted: | November 15, 2019 Key Record Dates |
| Last Update Posted: | May 17, 2022 |
| Last Verified: | May 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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:
In addition, access can be requested for all interventional clinical studies in patients:
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| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) 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/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Servier ( Institut de Recherches Internationales Servier ):
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AG-881 |
Additional relevant MeSH terms:
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Glioma Recurrence Disease Attributes Pathologic Processes Neoplasms, Neuroepithelial Neuroectodermal Tumors |
Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |