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A Phase II Dose-escalation Study Characterizing the PK of Eltrombopag in Pediatric Patients With Previously Untreated or Relapsed Severe Aplastic Anemia or Recurrent Aplastic Anemia

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ClinicalTrials.gov Identifier: NCT03025698
Recruitment Status : Recruiting
First Posted : January 19, 2017
Last Update Posted : August 5, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE January 12, 2017
First Posted Date  ICMJE January 19, 2017
Last Update Posted Date August 5, 2020
Actual Study Start Date  ICMJE September 30, 2017
Estimated Primary Completion Date April 1, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2017)
  • Eltrombopag PK parameter: AUCtau [ Time Frame: 2 weeks and 12 weeks after dose initiation ]
  • Eltrombopag PK parameter: Cmax [ Time Frame: 2 weeks and 12 weeks after dose initiation ]
  • Eltrombopag PK parameter: Ctrough [ Time Frame: 2 weeks and 12 weeks after dose initiation ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2017)
  • Percentage of participants with an overall response (OR) [ Time Frame: Week 12, Week 26, Week 52, and Week 78. ]
  • Percentage of participants with a platelet response. [ Time Frame: Week 12, Week 26, Week 52, and Week 78. ]
  • Incidence of clonal chromosomal population in bone marrow, myelodysplasia by morphology or acute leukemia [ Time Frame: Week 12, Week 26, Week 52 and Week 78. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Dose-escalation Study Characterizing the PK of Eltrombopag in Pediatric Patients With Previously Untreated or Relapsed Severe Aplastic Anemia or Recurrent Aplastic Anemia
Official Title  ICMJE A Phase II, Open-label, Non-controlled, Intra-patient Dose-escalation Study to Characterize the Pharmacokinetics After Oral Administration of Eltrombopag in Pediatric Patients With Refractory, Relapsed or Treatment Naive Severe Aplastic Anemia or Recurrent Aplastic Anemia
Brief Summary

This is a phase II, open label, multi-center, intra-patient dose escalation study to characterize the pharmacokinetics after oral administration of eltrombopag in combination with immunosuppressive therapy in pediatric patients with previously untreated or relapsed/refractory severe aplastic anemia or recurrent aplastic anemia.

All patients will be treated with eltrombopag for the 26-week Treatment Period, followed by a 52-week Follow-Up Period. Patients who have been previously untreated with immunosuppressive therapy will be treated according to the standard of care, hATG/cyclosporine, in addition to eltrombopag. Patients with relapsed/refractory SAA or recurrent AA will be enrolled into one of two treatment options: hATG/cyclosporine plus eltrombopag or cyclosporine plus eltrombopag, depending on prior treatment with immunosuppressive therapy.

After initiating treatment with eltrombopag, patients will have their dose assessed and modified as tolerated, until the targeted platelet count or maximum dose is achieved. Pharmacokinetic assessments will be performed at time points intended to capture steady state PK of the starting dose and highest dose achieved.

Upon completion of the Treatment and Follow-Up Periods, all patients will be offered the opportunity to enroll in an additional 3 year Long Term Follow-Up Period.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Aplastic Anemia
Intervention  ICMJE
  • Drug: Eltrombopag
    Tablet for oral use, once daily
  • Drug: hATG
    Horse ATG (ATGAM) (hATG) is not considered an investigational medicinal product (IMP)
  • Drug: CsA
    Cyclosporine (CsA) will be by supplied as either oral capsules or oral solution, administered twice a day
Study Arms  ICMJE
  • Experimental: Cohort A (Option 1)
    Interventions:
    • Drug: Eltrombopag
    • Drug: hATG
    • Drug: CsA
  • Experimental: Cohort A (option 2)
    Interventions:
    • Drug: Eltrombopag
    • Drug: CsA
  • Experimental: Cohort B
    Interventions:
    • Drug: Eltrombopag
    • Drug: hATG
    • Drug: CsA
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 16, 2017)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 30, 2027
Estimated Primary Completion Date April 1, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

For Cohort A:

  1. Prior history of diagnosis of SAA
  2. Diagnosis of relapsed/refractory SAA or recurrent AA following IST for SAA at the time of enrollment. Patients with recurrent AA (e.g., losing their response) are exempt from meeting the diagnostic criteria for relapsed SAA at the time of enrollment, but must have been previously diagnosed with SAA.
  3. Agree to concurrent eltrombopag treatment with appropriate, investigator-selected IST with either hATG + CsA or CsA.

    For Cohort B:

  4. Diagnosis of SAA at the time of enrollment
  5. Patients must not have been previously treated for SAA
  6. Patients must agree to treatment with hATG + CsA concurrent with eltrombopag.

    For all patients, regardless of cohort:

  7. Age 1 to <18 years
  8. Where appropriate, assessments to rule out congenital/inherited bone marrow failure syndromes and other causes of immune-mediated pancytopenia, which may be treated with transplant, must be completed prior to enrollment.
  9. Hematopoietic stem cell transplantation (HSCT) is not available or suitable as a treatment option or has been refused by the patient. (Candidacy for HSCT will be determined as per local practice.)
  10. Bone marrow aspirate and biopsy at any time during the 4 weeks prior to first dose of eltrombopag
  11. Normal karyotype with FISH for chromosomes 7 and 8
  12. Performance status score: Karnofsky ≥50 or Lansky ≥50 (depending on age)
  13. Serum creatinine ≤2.5 × ULN
  14. Total bilirubin ≤1.5 × ULN
  15. Written informed consent signed by a parent or legal guardian prior to initiation of any study specific procedure.

Exclusion Criteria:

  1. Prior and/or active medical history of:

    • Fanconi anemia (via chromosomal breakage test or growth arrest by flow cytometry)
    • Other known underlying congenital/inherited marrow failure syndromes
    • Symptomatic Paroxysmal Nocturnal Hemoglobinuria (PNH) and/or PNH clones >50% of PMN or RBC at time of enrollment
    • Any cytogenetic abnormalities, including but not limited to chromosome 7 or myelodysplasia, in bone marrow within 4 weeks of study enrollment
    • Myelodysplastic syndrome (MDS)
    • Other known or suspected underlying primary immunodeficiency
    • Any malignancy
  2. Active infection not responding to appropriate therapy
  3. Prior eltrombopag or other thrombopoietin receptor (TPO-R) agonist treatment for at least 2 months and a lack of response.
  4. Any out of range lab values Creatinine >2.5 × upper limit of normal (ULN), Total bilirubin >1.5 × ULN Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 × ULN
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Listed Location Countries  ICMJE Hong Kong,   Netherlands,   Portugal,   Russian Federation,   Thailand,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03025698
Other Study ID Numbers  ICMJE CETB115E2201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP