E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multicentric Castleman's disease |
|
E.1.1.1 | Medical condition in easily understood language |
Multicentric Castleman's disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050251 |
E.1.2 | Term | Castleman's disease |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to demonstrate that CNTO 328 in combination with BSC is superior to BSC in terms of durable tumor and symptomatic response among subjects with multicentric Castleman’s disease (MCD). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
• To demonstrate additional measures of efficacy (tumor response; duration of response; time to treatment failure; change in hemoglobin levels; ability to discontinue corticosteroids; and improvement in fatigue, physical function, and other disease-related symptoms)
• To study the safety of prolonged dosing
• To determine the pharmacokinetics of CNTO 328 among subjects with MCD
• To determine a baseline hepcidin value predictive of a ≥ 2 g/dL increase in hemoglobin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Measurable and symptomatic Multicentric Castleman's Disease
- Adequate organ function as assessed by laboratory values evaluated by the investigator to determine eligibility prior to treatment
- Eastern Cooperative Oncology Group performance status of 0, 1, or 2
- Corticosteroids dose that does not exceed 1 mg/kg/day of prednisone, and has remained stable or decreased over the 4 weeks before
treatment |
|
E.4 | Principal exclusion criteria |
- Human Immunodeficiency Virus or Human Herpes Virus-8 positive
- Skin lesions as sole measurable manifestation of Multicentric Castleman's Disease - Previous history of lymphoma
- Malignancies, except for adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or cancer other
than lymphoma, from which the patient has been disease-free for 3 or more years
- Concurrent medical condition or disease that may interfere with study participation
- Prior exposure to Interleukin-6 or Interleukin-6 receptor targeted therapies |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be durable tumor and symptomatic response. For definitions, see Section 9.2.2 of the protocol. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Treatment failure, discontinuation of treatment, withdrawal from the study, or until 48 weeks after the last subject starts study treatment, whichever occurs earlier. |
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E.5.2 | Secondary end point(s) |
- Duration of tumor and symptomatic response (whenever possible, treatment failure documented by the appearance of new lesions should be confirmed by histologic examination of the new lesions)
- Tumor response
- Duration of tumor response (whenever possible, tumor progression documented by the appearance of new lesions should be confirmed by histologic examination of the new lesions)
- Time to treatment failure
- Maximum change from baseline in hemoglobin in the absence of transfusion
- Proportion of subjects who are able to discontinue corticosteroids
|
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment failure, discontinuation of treatment, withdrawal from the study, or until 48 weeks after the last subject starts study treatment, whichever occurs earlier. |
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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 | 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 | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | Information not present in EudraCT |
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 |
Belgium |
Brazil |
Canada |
China |
Egypt |
France |
Germany |
Hong Kong |
Hungary |
India |
Israel |
Korea, Republic of |
Malaysia |
Netherlands |
New Zealand |
Norway |
Russian Federation |
Singapore |
Spain |
Taiwan |
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 study is defined as 5 years after the last subject starts study treatment. |
|
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 | 7 |
E.8.9.1 | In the Member State concerned days | 24 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 25 |