E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Follicular lymphoma is a type of blood cancer. It is the most common of the indolent (slow-growing) non-Hodgkin's lymphomas, and the second-most-common form of non-Hodgkin's lymphomas overall. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029473 |
E.1.2 | Term | Nodular (follicular) lymphoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To evaluate the objective response rate (ORR) of ME-401 in relapsed FL, defined as the best response rating of complete response (CR) or partial response (PR) according to the Lugano Response Criteria , as determined by an Independent Response Review Committee (IRRC)
2. To evaluate the tolerability of ME-401, defined as the rate of AEs requiring modified dosing schedule or study drug discontinuation (AERDM) |
1. Évaluer le taux de réponse objective (TRO) du ME-401 dans le LF en rechute, défini comme le meilleur taux de réponse en matière de réponse complète (RC) ou de réponse partielle (RP) selon les critères de réponse de Lugano , déterminé par un comité indépendant d’examen des réponses (CIER)
2. Évaluer la tolérance du ME-401, définie comme le taux d’événements indésirables (EI) nécessitant une modification du schéma posologique ou l’interruption du médicament à l’étude (EINMSPIME) |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of ME-401 as assessed by an IRRC:
o Duration of response (DOR) among subjects with an objective response
o Complete response (CR) rate
o Progression-free survival (PFS)
2.To evaluate the efficacy of ME-401 as assessed by the Investigator:
o Objective response rate (ORR)
o Duration of response (DOR) among subjects with an objective response
o Complete response (CR) rate
o Progression-free survival (PFS)
3.To evaluate overall survival (OS)
4.To evaluate the safety profile of ME-401
o Overall incidence of AEs
o Time to occurrence of AERDM
5.To evaluate the PK of ME-401 |
1. Évaluer l’efficacité du ME-401 évaluée par un CIER :
o Durée de la réponse (DR) chez les patients présentant une réponse objective
o Taux de réponse complète (RC)
o Survie sans progression (SSP)
2. Évaluer l’efficacité du ME-401 évaluée par l’investigateur :
o Taux de réponse objective (TRO)
o Durée de la réponse (DR) chez les patients présentant une réponse objective
o Taux de réponse complète (RC)
o Survie sans progression (SSP) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age ≥ 18 years (or age of majority)
2. Histologically confirmed diagnosis of FL as defined in the WHO classification scheme, limited to Grade 1, 2, or 3a
3. Progression of disease after at least 2 prior systemic therapies for FL. Subjects must have received an anti-CD20 antibody (minimum of 4 doses) and chemotherapy (minimum of 2 doses, which must have included an alkylating agent or a purine analogue), whether administered together or as successive treatments; radioimmunotherapy, high dose therapy and autologous stem cell transplantation, and CAR T-cell therapy are considered as one line of therapy |
1. Âge ≥ 18 ans (ou majorité)
2. Diagnostic de LF confirmé par un examen histologique défini dans le système de classification de l’Organisation mondiale de la santé (OMS), limité au grade 1, 2 ou 3a
3. Progression de la maladie après au moins 2 traitements systémiques antérieurs du LF. Les patients doivent avoir reçu un anticorps anti-CD20 (4 doses minimum) et une chimiothérapie (2 cycles minimum, qui doivent avoir inclus un agent alkylant ou un analogue de la purine), administrés conjointement ou successivement. La radio-immunothérapie, le traitement à forte dose et la greffe autologue de cellules souches et le traitement à base de cellules CAR-T sont considérés comme une intention de traitement. |
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E.4 | Principal exclusion criteria |
1. Known active histological transformation from FL to an aggressive lymphoma: biopsy documentation of the absence or presence of transformation is not required and left to the Investigator’s discretion
2. Major surgical procedure within 4 weeks of Day 1
3. Any uncontrolled clinically significant illness including, but not limited to, active infections, hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction
4. Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B core antibody plus have a positive hepatitis B PCR assay; subjects with a negative PCR assay are permitted with appropriate anti-viral prophylaxis
5. Positive HCV Ab; subjects with positive hepatitis C antibody are eligible if they are negative for HCV by PCR
6. Ongoing or history of drug-induced pneumonitis
7. Other diagnosis of cancer that is likely to require treatment in the next 2 years, with the exception of the following:
a. Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin
b. Curatively treated carcinoma in situ of the cervix
c. Hormonal therapy for prostate cancer |
1. Transformation histologique active connue du LF en lymphome agressif. Il n’est pas nécessaire de documenter l’absence ou la présence d’une transformation au moyen d’une biopsie, et cette opération est laissée à la discrétion de l’investigateur.
2. Intervention chirurgicale majeure dans les 4 semaines précédant le Jour 1 de l’étude.
3. Toute maladie cliniquement significative non contrôlée, notamment des infections actives, de l’hypertension, l’angine de poitrine, les arythmies, les maladies pulmonaires ou un dysfonctionnement auto-immun.
4. Patients avec un résultat positif pour l’antigène de surface du virus de l’hépatite B et/ou l’anticorps nucléocapsidique du virus de l’hépatite B et un résultat positif pour le test de réaction en chaîne par polymérase (PCR) pour l’hépatite B ; les patients dont le test PCR est négatif peuvent recevoir une prophylaxie antivirale appropriée.
5. Résultat positif pour les anticorps contre le virus de l’hépatite C (AcVHC) ; les patients présentant un résultat positif pour les anticorps contre le virus de l’hépatite C sont éligibles s’ils sont négatifs pour le VHC par PCR.
6. Pneumopathie d’origine médicamenteuse en cours ou passée.
7. Autre diagnostic de cancer susceptible de nécessiter un traitement au cours des 2 années suivantes, à l’exception des suivants :
a. Carcinome basocellulaire ou carcinome épidermoïde de la peau traité de manière curative
b. Carcinome in situ du col de l’utérus traité de manière curative
c. Hormonothérapie pour le cancer de la prostate |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are: 1) ORR defined as the best response of CR + PR as determined by an IRRC, and 2) the proportion of subjects requiring a modified dosing schedule or study drug discontinuation for CTCAE v5.0 Grade ≥ 2 AEs thought to be related or possibly related to the study drug. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
TBC: 1. meetings by IRRC for ORR 2. After the last patient has been on the study for 6 months. |
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E.5.2 | Secondary end point(s) |
1. Duration of Response (DOR)
DOR will be evaluated as a secondary endpoint and is defined as time from documentation of the first CR or PR to the time of disease progression or relapse (based on the Lugano Response Criteria) independently from study period or dosing schedule.
2.Progression-Free Survival (PFS)
PFS will be assessed as a secondary endpoint and is defined as time from initiation of treatment (Day 1) until disease progression or death from any cause independently from the study period or dosing schedule. PFS time will be censored at the last disease assessment date indicating the absence of progression or recurrence for subjects who have not demonstrated objective progression and are still alive. For subjects who withdraw consent for any reason before demonstrating evidence of progression or recurrence, PFS time will be censored at the last date for which disease assessment indicated the absence of progression or recurrence. Subjects are censored at the date of first dose of study treatment if no additional follow-up data are obtained.
3. Overall Survival (OS)
OS will be assessed as a secondary endpoint and is defined as time from initiation of treatment (Day 1) until death from any cause independently from the study period or dosing schedule. OS time will be censored at the last date the subject is known to be alive when the confirmation of death is absent or unknown. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After the last patient has been on the study for 6 months. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Belgium |
Canada |
France |
Germany |
Italy |
Korea, Republic of |
New Zealand |
Poland |
Spain |
Switzerland |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |