E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Low Tumor Burden Follicular Lymphoma (LTBFL) |
|
E.1.1.1 | Medical condition in easily understood language |
This is a disease of the lymph tissue (part of the immune system) that affects a type of white blood cell
called B-Lymphocytes. |
|
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 | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
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 |
To compare the efficacy of SAIT101 with rituximab (MabThera®) when administered as a first-line immunotherapy in patients with low tumor burden follicular lymphoma (LTBFL). |
|
E.2.2 | Secondary objectives of the trial |
To evaluate SAIT101 versus MabThera® with respect to:
• Safety and tolerability;
• Immunogenicity;
• Pharmacokinetics (PK) and pharmacodynamics (PD) in a sub population of patients. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic/pharmacodynamic optional substudy for a sub-population |
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E.3 | Principal inclusion criteria |
Patients with histologically-confirmed, Ann Arbor stage II – IVA CD20+ Follicular Lymphoma (FL) (Grades 1, 2, or 3a), aged at least 18 years, not previously treated for their FL, low tumor burden according to Groupe D’Etude des Lymphomes Folliculaires (GELF) criteria, Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1, at least one measurable lesion per the International Working Group (IWG) criteria 2007 at screening, no evidence of transformation to a large cell histology, and adequate hematological, renal, and liver function. |
|
E.4 | Principal exclusion criteria |
1.Previous treatment with any chemotherapy and/or rituximab or other monoclonal antibody.
2.Prior radiotherapy completed <28 days before study enrollment.
3.Anticipated need for concomitant administration of any other experimental drug, or a concomitant chemotherapy, anticancer hormonal therapy, radiotherapy, or immunotherapy during study participation.
4.Concomitant disease which requires continuous therapy with corticosteroids at doses equivalent to prednisolone >20 mg/day.
5.Leukemia or transformation to diffuse large B cell lymphoma secondary to previously untreated follicular lymphoma.
6.Prior or concomitant malignancies within 5 years prior to screening, with the exceptions of non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, adequately treated breast cancer in situ, and localized prostate cancer stage T1c, provided that the patient underwent curative treatment and remains relapse free.
7.Patients with a body surface area >3.0 m2.
8.Major surgery (excluding lymph node biopsy) within 28 days prior to randomization.
9.Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus (HIV) infection or positive test at screening.
10.Acute, severe infection (e.g., sepsis and opportunistic infections), or active, chronic or persistent infection that might worsen with immunosuppressive treatment (e.g., herpes zoster).
11.Positive serological test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology. Patients with a negative HBsAg and positive HBcAb must have a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level <20 IU/mL (or 112 copies/mL) by polymerase chain reaction (PCR). These HBV patients must be willing to undergo PCR HBV DNA testing during treatment and may participate following consultation with a hepatitis expert regarding monitoring and use of HBV antiviral therapy, and provided they agree to receive treatment as indicated. An HBV re-test will be performed at each study visit from Week 5 onwards, and at the discretion of the Investigator.
Patients with a positive test because of HBV vaccine may be included (i.e., anti-HBs+, anti-HBc–).
Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV ribonucleic acid (RNA).
12.Confirmed current active tuberculosis (TB). Patients with latent TB as determined by tuberculosis skin testing (e.g. Mantoux test) or interferon-gamma release assay (IGRA e.g.QuantiFERON-TB test) may be enrolled if such patients have written confirmation from their health care provider (e.g., Pulmonologist or Infection Specialist) of adequate prophylaxis before or within the screening period, and no evidence of tuberculosis on a chest X-ray performed within 3 months of Day 1 or chest CT.
13.Central nervous system (CNS) or meningeal involvement, or cord compression by the lymphoma; history of CNS lymphoma. A brain (CT or MRI) scan should be conducted at screening ONLY if lesions are suspected on the brain, to exclude patients with brain localization of FL.
14.History of a severe allergic reaction or anaphylactic reaction to a biological logical agent or history of hypersensitivity to any component of the trial drug (e.g., hypersensitivity or allergy to murine products).
15.Patients who have significant cardiac disease, including but not limited to history of congestive heart failure (New York Heart Association Class III/IV; see Appendix 7), unstable angina, or uncontrolled cardiac arrhythmia.
16.Uncontrolled or severe hypertension, or cerebrovascular disease.
17.Serious underlying medical conditions that, per the Investigator’s discretion, could impair the ability of the patient to participate in the trial (including but not limited to ongoing active infection, severe immunosuppression, uncontrolled diabetes mellitus, gastric ulcers, or active autoimmune disease).
18.Any other co-existing medical or psychological condition(s) that will preclude participation in the study or compromise ability to give informed consent and/or comply with study procedures.
19.Treatment with any investigational medicinal product (IMP) within 4 weeks prior to initiation of 1st infusion of study drug, or treatment with a drug that has not received regulatory approval for any indication within 4 weeks or a minimum of 5 half-lives, whichever is longer, of the 1st infusion of study drug.
20.Receipt of a live/attenuated vaccine within 6 weeks prior to the screening visit.
21.Females who are pregnant, breastfeeding, or planning a pregnancy during the treatment period or within 12 months after the last infusion of study drug.
22.Patients who are investigational site staff members directly involved in the conduct of the trial, and their family members, site staff members otherwise supervised by the investigator, or patients who are Archigen employees directly involved in the conduct of the trial. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint:
Overall Response Rate (ORR) (Complete Response [CR] + Partial Response [PR]) at Week 28 as defined by IWG criteria 2007 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
at Week 28 as defined by IWG criteria 2007 |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints:
Tumor response evaluations as defined by the revised IWG Criteria 2007, for malignant lymphoma:
Overall Response Rate (ORR)
Complete Response (CR)
Partial Response (PR)
Stable Disease (SD)
Progressive disease (PD)
Time to event (TTE), defined as the time from the date of randomization to the date when an event occurs; an event is disease progression, death due to any cause, or the start of new treatment for FL, whichever comes first
drug concentration,
CD19 + B-cell count and
immunogenicity. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
For assessment of ORR + CR + PR + SD + PD = weeks 12 and 28 + unscheduled visit as per table 1 (CT scan)
For TTE, it is at any time or visits (from weeks 1/2/3/4/5/12/20/28/36/52) or at any unscheduled visit
For drug concentration (PK) = weeks 1/2/3/4/5/12/20/28
For CD19 + B-cell count (hematology) = weeks 1/2/3/4/5/12/20/28/36/52 + unscheduled visit
For immunogenicity = weeks 1/2/3/4/5/12/20/28/36/52 + unscheduled visit |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Belarus |
Bosnia and Herzegovina |
Bulgaria |
Chile |
Croatia |
Czech Republic |
Egypt |
France |
Georgia |
Germany |
Guatemala |
Hong Kong |
Hungary |
India |
Italy |
Korea, Republic of |
Latvia |
Mexico |
Panama |
Philippines |
Romania |
Saudi Arabia |
Serbia |
South Africa |
Spain |
Thailand |
Turkey |
Ukraine |
United Kingdom |
United States |
|
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
|
The end of the study is defined as ‘the last visit of the last patient undergoing the study'. |
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |