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 |
Disease is characterized by chronic inflammation, acute and chronic pain, fatigue and chronic hemolytic anemia with recurrent vaso-occlusive crises. |
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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 | PT |
E.1.2 | Classification code | 10040641 |
E.1.2 | Term | Sickle cell anaemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
To determine the effect of canakinumab versus placebo on daily pain experienced by sickle cell anemia patients |
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E.2.2 | Secondary objectives of the trial |
-To determine the duration of effects of canakinumab versus placebo on daily pain experienced by SCA patients (Reduction of average daily pain
VAS over 4-week intervals up to Week 24 as compared to baseline
levels)
- To determine the effect of canakinumab versus placebo on laboratory markers of inflammation (Week 12 versus baseline of: Serum hsCRP, WBC count, Absolute counts of blood neutrophils, Absolute counts of blood monocytes).
- To determine the effect of canakinumab versus placebo on laboratory and functional markers of hemolysis.
- To determine the effect of canakinumab versus placebo on SCA-related days missed from school or work
-To determine the effect of canakinumab vs placebo on reducing the need for acute blood transfusion
- To assess the safety and tolerability of canakinumab in patients with SCA as measured by adverse events (AEs), including immunogenicity as indicated by the presence of anti-drug antibodies
- To determine the PK of canakinumab in SCA patients
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female subjects ages 8-20 years of age (both inclusive) diagnosed with sickle cell anemia (HbSS) or sickle beta0 thalassemia (documented by family studies, or analysis of either hemoglobin or DNA).
- Patient’s written informed consent from those ≥18 years of age must be obtained before any assessment is performed. Parent or legal guardian’s written informed consent and child’s assent, if appropriate, are required before any
assessment is performed for patients < 18 years of age.
- Detectable baseline of background or episodic pain measured by daily e-diary over 1 to 2 weeks during screening period as defined below:
Average daily pain score ≥ 1 cm without analgesic use over a period of at least 7 days and/or, At least one episode of pain requiring analgesic use during a period of up to 14 days.
- History of ≥2 vaso-occlusive pain episodes in the past year, as defined as pain with no other, non-sickle cell identifiable cause that requires analgesia and interferes with the patient's normal daily routine.
Other inclusion criteria as per full protocol may apply. |
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E.4 | Principal exclusion criteria |
- History of anaphylactic reaction or known hypersensitivity to canakinumab or any component thereof.
- History of, or ongoing treatment with chronic red blood cell transfusion therapy, or have evidence of iron overload requiring chelation therapy.
- Transcranial Doppler ultrasound in the past year in patients with an
accessible transtemporal window demonstrating velocity in middle or anterior cerebral or internal carotid artery y ≥200 cm/sec.
- Administration of any other blood products within 3 weeks prior screening visit.
Other exclusion criteria as per full protocol may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction of average daily pain VAS over the period of Week 8 to 12 as compared to baseline levels |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Reduction of average daily pain VAS over 4-week intervals up to Week
24 as compared to baseline levels
Week 12 versus baseline of:
- Serum hs-CRP
- WBC count
- Absolute counts of blood neutrophils
- Absolute counts of blood monocytes
Week 12 versus baseline of:
- Hemoglobin concentration
- Reticulocyte count
- Haptoglobin
- LDH
- - bilirubin (total, direct, indirect)
- Oxygen percent saturation (SaO2)
- Number of days absent from school or work due to pain as recorded by
daily e-diary
- the rate of SCA-related acute transfusion
- Adverse events in patients taking ACZ885 compared to placebo up to a
total of 56 weeks treatment
- Serial serum PK determinations in patients with SCA |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
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 |
Canada |
Germany |
Israel |
South Africa |
Turkey |
United Kingdom |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 28 |