E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immune (idiopathic) thrombocytopenic purpura (ITP) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021245 |
E.1.2 | Term | Idiopathic thrombocytopenic purpura |
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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 objective of the study is to compare the ability of AMG 531 versus medical standard of care (SOC) to prevent a splenectomy and to provide a durable treatment option for immune (idiopathic) thrombocytopenic purpura (ITP) non-splenectomized adult subjects during the 52- week treatment period. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to observe the impact of AMG 531 on various ITP symptoms and platelet parameters compared to medical SOC for ITP. These include the time to splenectomy, platelet response, and the change in ITP Patient Assessment Questionnaire (PAQ) Physical Health domains of Symptoms, Bother, Activity, and Fatigue. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject is = 18 years of age. - Subject has a diagnosis of ITP according to ASH guidelines. - If subject is > 60 years of age, subject has a written bone marrow biopsy report confirming the diagnosis of ITP. - Subject has received at least 1 prior therapy for ITP. - Subject has a platelet count < 50 x 109/L or their platelet count falls to < 50 x 109/L during or after a clinically- indicated taper or discontinuation of current ITP therapy. - Before any study- specific procedure, the appropriate written informed consent must be obtained (see Section 12.1). |
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E.4 | Principal exclusion criteria |
- Subject has had a splenectomy for any reason. - Subject has an active malignancy. - Subject has a history of cancer, other than basal cell carcinoma or cervical carcinoma in situ, with treatment or active disease within 5 years. - Subject has a known history of bone marrow stem cell disorder, • Abnormal bone marrow findings, other than those typical of ITP, must be approved by Amgen before a subject may be enrolled in the study. - Subject has participated in any study evaluating PEG- rHuMGDF, recombinant human thrombopoietin (rHuTPO), AMG 531, or a thrombopoietic protein. - Subject is receiving other investigational agents or procedures. - Subject is currently enrolled in, or has completed within the last 30 days, another investigational device or drug study. - Subject is pregnant or breast feeding. - Subject is not using adequate contraceptive precautions. - Subject has known sensitivity to any recombinant E coli- derived product. - Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and does not have a legally acceptable representative. - Subject has any kind of disorder that compromises the ability of the subject to comply with study procedures. |
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E.5 End points |
E.5.1 | Primary end point(s) |
This study has 2 primary endpoints, 1 related to splenectomy and the other related to treatment failure. The first primary endpoint will be the number of subjects undergoing a splenectomy by treatment group during the 52-week treatment period. The second primary endpoint will be the number of subjects with a treatment failure during the 52-week treatment period. Treatment failure is defined as:
• a lack of efficacy defined as platelet count < 20 x 109/L for 4 consecutive weeks at the highest recommended dose and schedule (AMG 531 – 10 ug/kg weekly; medical SOC for ITP – apply standard institutional practices or therapeutic guidelines); or,
• a major bleeding event; or,
• a change in therapy due to an intolerable side effect or bleeding symptoms (including a minor bleeding event). A minor bleeding event is defined as “ dry” or “ wet” purpura (eg, petechiae, mucosal bleeding from the gums or nose). A major bleeding event is defined as a hemorrhage (eg, upper or lower gastrointestinal tract, genitourinary tract or central nervous system). The primary statistical hypothesis will be that the corresponding rates in the AMG 531 arm will be lower compared to the medical SOC for ITP arm in both the proportion of subjects having a splenectomy and the proportion of subjects with a treatment failure within the 52-week treatment period. The study will declare a success with AMG 531 treatment if the tests for both primary efficacy endpoints are statistically significant in favor of AMG 531 arm over the medical SOC for ITP arm. |
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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 | 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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard of Care as defined by international treatment guidelines and local medical practice |
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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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 89 |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |