AGIOS AG881-C-004
Research type
Research Study
Full 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
IRAS ID
1003209
Contact name
Catherine McBain
Contact email
Sponsor organisation
Agios Pharmaceuticals, Inc
Eudract number
2019-002481-13
Clinicaltrials.gov Identifier
Research summary
AG881-C-004 is a clinical research study that is designed to evaluate the safety and
efficacy (usefulness) of AG-881 as compared to placebo (a medically inactive substance)
in participants with residual or recurrent Grade 2 glioma that has an IDH1 or IDH2
mutation. The patient will be randomly assigned (like flipping a coin) to receive either
AG-881 or placebo in this study. The patient will have a 50/50 chance of being assigned
to either of the study groups. The patient, the study doctor, site staff, and the Sponsor of
the study will not know which study drug the patient is assigned to, this is called blinded
study treatment. In case of an emergency, however, the study doctor can get this
information.
There is a protein inside the patient’s cells called IDH that is involved in a process
called metabolism, which is the process of providing the patient’s body’s cells with
energy from nutrients. There are two main types of IDH proteins in the body, called
IDH1 and IDH2. Abnormal changes in the protein (mutations) can be found in certain
types of cancer including glioma. These mutations result in an abnormal form of the IDH
protein in the cancer cells. Most IDH mutations in glioma are found in IDH1.
When IDH1 and/or IDH2 is mutated, it produces an excess amount of a substance
present in cells called 2 hydroxyglutarate (2-HG), which is present in low levels in
normal cells. When 2-HG is present in excessive amounts, it results in changes within the
cells, which can result in cancer, including glioma. As part of molecular pre-screening,
the patient’s tumour tissue is tested to see if it was positive for IDH1 or IDH2 mutations.
The patient will only be enrolled in this study and given AG-881 or placebo if the
patient’s tumour tissue is positive for mutation in IDH1 or IDH2 and he/ she meets the
other eligibility criteria required. The purpose of this study is to improve or otherwise
manage the participant’s patient’s health, but the purpose of research is to gather
information to advance science and medicine.
It is estimated that approximately 366 adolescents and adults will take part in this study.
AG-881 is a new investigational drug in development by the Sponsor to potentially treat
patients with glioma. AG-881 is a drug that is designed to block the abnormal IDH1 and
IDH2 protein in cancer cells. Investigational means that AG-881 has not been approved
for use either alone or in combination with any drug by the U.S. Food and Drug
Administration (FDA) or any other health authority. AG-881 may stop the abnormal
IDH1 and/or IDH2 protein and lower the level of 2-HG.
The placebo is a tablet that looks exactly like AG-881 but does not contain any AG-881.
It does not contain any substance that is designed to have any effect on participants or
the disease. At the start of the study, the participant will not know if he/she is receiving
placebo or AG-881. The participant will be asked to take study drug every day without
interruption beginning on the first day of Cycle 1. Administration of the study drug will
continue until the disease worsens, development of other unacceptable side effects
occurs, there is a need for more aggressive therapy in the opinion of the study doctor, the
patient has a confirmed pregnancy, death occurs, he/ she withdraws consent from overall
study participation, the patient is lost to follow-up, the study doctor decides it is in the
patient’s best interest to stop study drug, or the Sponsor ends the study, whichever
occurs first.
In addition, if the disease worsens based on scans of the patient’s disease while the
patient is in the study, the patient may be told whether he/ she was receiving AG-881 or
placebo by the study doctor. If the patient was receiving placebo and the patient meets
certain eligibility criteria, he/ she will be given the opportunity to receive AG-881 as part
of the study.
After the patient has stopped taking study drug as part of the study, he/ she will be
contacted by the study doctor or site staff by phone every 6 months beginning at the Endof-
Study Treatment visit to see how the patient is doing and if he /she has started any new
anti-cancer treatments for a period of no more than 5 years after the last patient enrolls
into the study, or until all patients have died, withdrawn consent from overall study
participation, are lost to follow-up, or the Sponsor ends the study, whichever occurs first.REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
20/NW/0260
Date of REC Opinion
17 Jul 2020
REC opinion
Further Information Favourable Opinion