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Clinical Trials/2022-502335-19-00
2022-502335-19-00
Completed
Phase 3

A Phase 3, Open-Label, Single-arm, Multicenter Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Activity, and Safety of Ravulizumab Administered Subcutaneously in Pediatric Participants (2 to < 18 years of age) with Paroxysmal Nocturnal Hemoglobinuria (PNH) or Atypical Hemolytic Uremic Syndrome (aHUS)

Alexion Pharmaceuticals Inc.7 sites in 2 countries14 target enrollmentStarted: August 2, 2023Last updated:
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Overview

Phase
Phase 3
Status
Completed
Enrollment
14
Locations
7
Primary Endpoint
Summary statistics of ravulizumab concentrations at Day 1 postdose, Day 15 predose, Day 15 postdose, and Day 71 predose Summary statistics of serum free C5 concentrations at Day 1 postdose, Day 15 predose, Day 15 postdose, and Day 71 predose
OverviewEligibility CriteriaOutcomesInvestigatorsSitesRecords & IdentifiersSimilar Trials

Overview

Brief Summary

To characterize the PK and PD of treatment with ravulizumab SC in pediatric participants with PNH or aHUS

Eligibility Criteria

Ages
0 years to 64 years (0-17 Years, 18-64 Years)
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • •Must be 2 to < 18 years of age at the time of informed consent
  • •Inclusion Criteria Specific for PNH Cohort:
  • •Documented diagnosis of PNH confirmed by high-sensitivity flow cytometry evaluation (Borowitz, 2010) of red blood cells (RBCs) and white blood cells (WBCs), with granulocyte or monocyte clone size of ≥ 5%
  • •Complement inhibitor treatment-naïve participants must have the presence of 1 or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia, history of a MAVE (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red blood cell transfusion due to PNH.
  • •LDH values at Screening as follows: a. Complement inhibitor treatment-naïve participants must have LDH ≥ 1.5 × ULN analyzed by the central laboratory b. Eculizumab- or ravulizumab-experienced participants must have LDH ≤ 1.5 × ULN (sample must be obtained within 1 day prior to the scheduled eculizumab/ ravulizumab dosing day [ie, at trough eculizumab/ravulizumab level] and analyzed by the central laboratory)
  • •Inclusion Criteria Specific for aHUS Cohort: Complement inhibitor treatment-naïve participants must have evidence of TMA, including thrombocytopenia, evidence of hemolysis, and kidney injury, based on the following laboratory findings: a. Platelet count < 150000/μL during the Screening Period or within 28 days prior to the start of the Screening Period, and b. LDH ≥ 1.5 × ULN for age and sex during the Screening Period or within 28 days prior to the start of the Screening Period, and c. Hemoglobin ≤ lower limit of normal (LLN) for age and sex during the Screening Period or within 28 days prior to the start of the Screening Period, and d. Serum creatinine level ≥ 97.5th percentile for age at Screening (participants who require dialysis for acute kidney injury are also eligible regardless of serum creatinine level)
  • •Eculizumab- or ravulizumab-experienced participants must have confirmed diagnosis of aHUS including all of the following laboratory findings documented by local laboratories at the time of the TMA event: a. Increase in LDH > ULN, and b. Increase in serum creatinine > ULN, and c. Decrease in platelets < LLN
  • •Eculizumab- or ravulizumab-experienced participants must have clinical evidence of response to eculizumab or ravulizumab indicated by stable TMA parameters (via central laboratory results) at Screening, including: a. LDH < 1.5 × ULN, and b. Platelet count ≥ 150000/μL, and c. Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73m2 using the Schwartz formula
  • •Among participants with a kidney transplant: a. Known history of aHUS prior to current kidney transplant, or b. No known history of aHUS, and persistent evidence of TMA at least 4 days after modifying the immunosuppressive regimen (eg, suspending or reducing the dose) of calcineurin inhibitor ([CNI]; eg, cyclosporine, tacrolimus) or mammalian target of rapamycin inhibitor ([mTORi]; eg, sirolimus, everolimus)
  • •Among participants with onset of TMA postpartum, persistent evidence of TMA for > 3 days after the day of childbirth.

Exclusion Criteria

  • •History of bone marrow transplantation
  • •Unstable medical conditions (eg, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of Day 1, coexisting chronic anemia unrelated to PNH) that would make participants unlikely to tolerate the requirements of the protocol
  • •Known medical or psychological condition(s) or risk factor that, in the opinion of the Investigator, might interfere with the participant’s full participation in the study, pose any additional risk for the participant, or confound the assessment of the participant or outcome of the study
  • •Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to the start of the Screening Period
  • •History of hypersensitivity reactions to: a. Commonly used antibacterial agents, including beta-lactams, penicillin, aminopenicillins, fluoroquinolones (specifically including ciprofloxacin), cephalosporins, and carbapenems, which in the opinion of the Investigator would make it ifficult to properly provide either empiric antibiotic therapy or treat an active infection b. Any ingredient contained in the study intervention, including hypersensitivity to murine proteins
  • •Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to study entry
  • •Participation in another experimental therapy or investigational device study within 4 weeks before initiation of study intervention on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater (except for participation in observational studies [eg, PNH Registry])
  • •Received any other experimental C5 antagonist at any time
  • •Pregnant, breastfeeding, or intending to conceive during the course of the study
  • •Inability for participant/caregiver to complete the requirements for SC self-administration

Outcomes

Primary Outcomes

Summary statistics of ravulizumab concentrations at Day 1 postdose, Day 15 predose, Day 15 postdose, and Day 71 predose Summary statistics of serum free C5 concentrations at Day 1 postdose, Day 15 predose, Day 15 postdose, and Day 71 predose

Summary statistics of ravulizumab concentrations at Day 1 postdose, Day 15 predose, Day 15 postdose, and Day 71 predose Summary statistics of serum free C5 concentrations at Day 1 postdose, Day 15 predose, Day 15 postdose, and Day 71 predose

Secondary Outcomes

  • PK and PD (Both Cohorts) Serum ravulizumab concentrations over time through Week 52 Absolute values, change from baseline, and percentage change from baseline for free serum C5 concentrations over time through Week 52
  • Efficacy (PNH Cohort Only) Percentage change from baseline in LDH to Week 10 and Week 52 Incidence of BTH through Week 10 and Week 52 Achievement of transfusion avoidance through Week 10 and Week 52 Achievement of stabilized hemoglobin through Week 10 and Week 52 Change from baseline in PNH RBC clone size at Week 52
  • Efficacy (aHUS Cohort Only) Dialysis requirement status through Week 10 and Week 52 Observed value and change from baseline in eGFR through Week 10 and Week 52 Observed value and change from baseline in serum creatinine through Week 10 and Week 52 Observed value and change from baseline in hematologic parameters through Week 10 and Week 52: • Platelets • LDH • Hemoglobin
  • Health-related QoL (Both Cohorts) Change from baseline in patient-reported fatigue, as measured by Pediatric FACIT-Fatigue (participants ≥ 8 years of age) to Week 10 and Week 52 Change from baseline in PedsQL 4.0 Generic Core Scale to Week 10 and Week 52
  • Safety (Both Cohorts) Incidence of AEs and SAEs Incidence of ADEs and serious ADEs in participants treated with ravulizumab SC via OBI
  • Device Performance (Both Cohorts) Reported outcome of attempted full-dose administration via OBI Reported device deficiencies/complaints and associated device investigations
  • Immunogenicity (Both Cohorts) ADA incidence, response categories and titer in study participants treated with ravulizumab SC for the duration of the study

Investigators

Sponsor Class
Pharmaceutical company
Responsible Party
Principal Investigator
Principal Investigator

Masayo Ogawa

Scientific

Alexion Pharmaceuticals Inc.

Study Sites (7)

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