Tested in adult and paediatric immune thrombocytopenia (ITP) patients across 5 clinical trials
A phase III study evaluating the safety, tolerability and efficacy of Revolade in patients with ITP
Inclusion criteria2
Age: ≥18 years
Diagnosis: chronic ITP (defined as >6 months’ duration with baseline platelet counts <30,000/μL)
Previous treatment: patients had responded to 1 or more previous ITP treatments
Splenectomy status: splenectomised or non-splenectomised
197 patients randomised (2:1)
- REVOLADE + local standard of care: n=135
- Placebo + local standard of care: n=62
- REVOLADE starting dose: 50 mg once daily
- Dose modifications were made on the basis of individual platelet response (dose increases to a maximum of 75 mg/day and decreases to 25 mg/day)
- Treatment duration: 6 months
The odds of response to REVOLADE (defined as platelet count of 50,000–400,000/μL) vs. placebo over 6 months of treatment
- Median platelet count
- Proportion of patients responding at ≥75% of assessments
- Mean cumulative weeks of response
- Mean maximum weeks of continuous response
- Bleeding symptoms*
- Reduction of baseline treatment for ITP
- Use of rescue medicine
A phase III study evaluating the safety, tolerability and efficacy of REVOLADE in patients with ITP
Age: ≥18 years
Diagnosis: chronic ITP (defined as >6 months duration with baseline platelet counts between 20,000/μL and 50,000/μL)
Previous treatment: patients had received 1 or more previous ITP treatments
66 patients enrolled
- REVOLADE 50 mg once daily over 3 cycles
- Patients with platelet counts <50,000/μL for 2 successive weeks could receive 75 mg on or after Day 22 during the on-therapy treatment periods
- Dose decreases were not permitted
- A treatment cycle consisted of an on-therapy period of up to 6 weeks followed by an off-therapy period of up to 4 weeks. Patients who did not respond in Cycle 1 were not eligible to continue with further cycles of treatment
Consistency of response, defined as the proportion of patients with a response (platelet count ≥50,000/μL and at least twice the baseline) in Cycle 1 who also responded to REVOLADE in Cycle 2 or 3
- The proportion of patients who achieved a platelet count ≥50,000/μL and at least double the baseline value in at least 80% of assessments during Weeks 2–6 of study treatment in each cycle
- The proportion of patients requiring rescue treatment over 3 cycles
- The incidence and severity of bleeding assessed with the WHO bleeding scale
- Safety and tolerability
A phase III, open-label, extension study evaluating the long-term safety and efficacy of Revolade in adult patients with ITP1
Age: ≥18 years
Diagnosis: chronic ITP (defined as >6 months duration with baseline platelet counts <30,000/μL)
Previous treatment: patients had an insufficient response to 1 or more previous ITP treatments. Patients had been treated with REVOLADE in previous trials
Splenectomy status: splenectomised or non-splenectomised
302 patients enrolled
- REVOLADE starting dose: 50 mg once daily
- Dose modifications were made on the basis of individual platelet response (dose increases to a maximum of 75 mg/day and decreases 25mg/day or less if platelet counts were too high)
Safety and tolerability parameters including laboratory tests, ocular tests and frequencies of all adverse events
- Proportion of patients achieving platelet count thresholds (≥30,000/μL and ≥50,000/μL) during treatment
- Maximum continuous duration of platelet count thresholds
- Reduction or sparing of concomitant ITP therapies while maintaining a platelet count ≥50,000/μL
- Proportion of patients achieving stable platelet counts ≥50,000/μL while remaining free of concomitant ITP medication during treatment
- Proportion of patients needing rescue treatment
- Incidence and severity of signs and symptoms associated with ITP (measured using the WHO bleeding scale and ITP bleeding score)
A phase II open-label study evaluating the safety, tolerability and efficacy of REVOLADE in paediatric patients with ITP
Age: 1–17 years
Diagnosis: persistent and chronic ITP (defined as >6 months duration and platelets counts <30,000/μL)
Previous treatment: patients had received at least one previous ITP treatment
67 patients randomised (2:1)
- REVOLADE: n=45
- Placebo: n=22
- REVOLADE starting dose:
– Patients aged 12–17 years: 37.5 mg/day
– Patients aged 6–11 years: 50 mg/day for patients ≥27 kg (25 mg/day for east Asian patients) or 25 mg/day for patients <27 kg (12.5 mg/day for east Asian patients)
– Patients aged 1–5 years: 1.5 mg/kg/day (0.8 mg/kg once per day for east Asian patients)
- Dose modifications where made on the basis of platelet response up to a maximum dosage of 75 mg/day or 2 mg/kg
The proportion of patients achieving a platelet count ≥50,000/μL at least once from Weeks 1 to 6 (Days 8 to 43) of the randomised phase of the study in the absence of rescue therapy
- Safety and tolerability of REVOLADE treatment for 24 weeks
- The proportion of patients achieving platelet counts of ≥50,000/μL in at least 60% of assessments from Weeks 2–6 (Days 15 to 43)
- The proportion of patients achieving platelet counts of ≥50,000/μL at least once during 24 weeks of treatment
- Reduction or discontinuation of concomitant ITP treatment for and need for rescue medication
- Reduction in bleeding symptoms, in accordance with the WHO bleeding scale
- Effects of treatment on quality of life
- Pharmacokinetics
A phase II open-label study evaluating sustained response of REVOLADE treatment in paediatric patients with ITP
Age: 1–17 years
Diagnosis: chronic ITP (defined as >12 months duration and platelets counts <30,000/μL)
Previous treatment: patients had received at least one previous ITP treatment
92 patients randomised (2:1)
- REVOLADE: n=63
- Placebo: n=29
- REVOLADE starting dose:
– Patients aged 6–17 years: 25 mg/day to 50mg/day based on bodyweight and ethnic origin
– Patients aged 1–5 years: 1.2 mg/kg/day (0.8 mg/kg once per day for east Asian patients)
- Dose modifications where made on the basis of platelet response up to a maximum dosage of 75 mg/day
The primary outcome was the proportion of patients achieving a platelet count ≥50,000/μL for ≥6 weeks from Weeks 5–12 of the double-blind period in the absence of rescue therapy
- Both double-blind and open-label period
– Safety
– Need for rescue treatment
– Incidence of WHO-classified bleeding
– Maximum continuous platelet response ≥50,000/μL
- Double-blind period
– Weighted mean platelet change up to Week 12
– The proportion of patients achieving platelet counts ≥50,000/μL any time during the first 6 weeks and 12 weeks in the absence of rescue therapy
– Odds ratio of patient achieving platelet count ≥50,000/μL at least once from Weeks 1–12 in the absence of rescue therapyL
- Open-label period
– Safety
– The proportion of patients achieving platelet counts ≥50,000/μL any time from 4 weeks and 24 weeks in the absence of rescue therapy
– Reduction or discontinuation of concomitant ITP medication
Choose REVOLADE with confidence for a tested ITP treatment1–5
ITP, immune thrombocytopenia; WHO, World Health Organization.
*Assessed with WHO bleeding scale.
References:
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Wong R, et al. Blood. 2017;130:2527–2536.
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Cheng G, et al. Lancet. 2011;377:393–402.
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Bussel J, et al. Br J Haematol. 2013;160:538–546.
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Bussel J, et al. Lancet. 2015:315–325.
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Grainger J, et al. Lancet. 2015;386:1649–1658.