Prescribing information

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

Number of patients2

197 patients randomised (2:1)

  • REVOLADE + local standard of care: n=135
  • Placebo + local standard of care: n=62
REVOLADE treatment regimen2
  • 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
Primary endpoint2

The odds of response to REVOLADE (defined as platelet count of 50,000–400,000/μL) vs. placebo over 6 months of treatment

Secondary endpoints2
  • 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

Inclusion criteria3

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

Number of patients3

66 patients enrolled

REVOLADE treatment regimen3
  • 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
Primary endpoint3

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

Secondary endpoints3
  • 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

Inclusion criteria1

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

Number of patients1

302 patients enrolled

REVOLADE treatment regimen1
  • 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)
Primary endpoint1

Safety and tolerability parameters including laboratory tests, ocular tests and frequencies of all adverse events

Secondary endpoints1
  • 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

Inclusion criteria4

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

Number of patients4

67 patients randomised (2:1)

  • REVOLADE: n=45
  • Placebo: n=22
REVOLADE treatment regimen4
  • 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
Primary endpoint4

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

Secondary endpoints4
  • 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

Inclusion criteria5

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

Number of patients5

92 patients randomised (2:1)

  • REVOLADE: n=63
  • Placebo: n=29
REVOLADE treatment regimen5
  • 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
Primary endpoint5

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

Secondary endpoints5
  • 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:
  1. Wong R, et al. Blood. 2017;130:2527–2536.
  2. Cheng G, et al. Lancet. 2011;377:393–402.
  3. Bussel J, et al. Br J Haematol. 2013;160:538–546.
  4. Bussel J, et al. Lancet. 2015:315–325.
  5. Grainger J, et al. Lancet. 2015;386:1649–1658.
 
IE | May 2022 | 174745
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Reporting suspected adverse reactions of the medicinal product is important to Novartis and the HPRA. It allows continued monitoring of the benefit/risk profile of the medicinal product. All suspected adverse reactions should be reported via HPRA Pharmacovigilance, website: www.hpra.ie. Adverse events could also be reported to Novartis preferably via www.report.novartis.com or by email:[email protected] or by calling 01 2080 612.