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)
- Conditions
- Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) or Atypical Hemolytic Uremic Syndrome (aHUS)MedDRA version: 20.1Level: LLTClassification code: 10079841Term: Atypical hemolytic uremic syndrome Class: 10005329MedDRA version: 21.1Level: LLTClassification code: 10055629Term: Paroxysmal nocturnal hemoglobinuria Class: 10038359Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- CTIS2022-502335-19-00
- Lead Sponsor
- Alexion Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 22
Must be 2 to < 18 years of age at the time of informed consent, Inclusion Criteria Specific for PNH Cohort: 10. 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., Male or female, Female participants of childbearing potential and male participants must be willing to follow protocol-specified contraception guidance, Body weight = 10 kg at Screening, To reduce the risk of meningococcal infection (N meningitidis), all participants must be vaccinated against meningococcal infection from serogroups A, C, Y, W135, an
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, Inability to travel to the clinic for specified visits during the Primary Evaluation Period or fulfil the logistic requirements of study intervention administration, History of N meningitidis infection, Exclusion Criteria Specific for PNH Cohort: More than 1 LDH value > 2 × ULN within the 3 months prior to study entry (eculizumab-experienced participants or ravulizumab-experienced participants only), MAVE in the 6 months prior to study entry (eculizumab-experienced participants or ravulizumab-experienced participants only), Platelet count < 30,000/mm3 (30 × 109/L) at Screening, Absolute neutrophil count < 500/µL (0.5 × 109/L) at Screening, Exclusion Criteria Specific for aHUS Cohort: Hemolytic uremic syndrome related to known genetic defects of cobalamin C metabolism, Identified drug exposure-related HUS, Any known abnormal TMA parameters within 90 days prior to screening (ie, LDH = 1.5 × ULN, or platelet count < 150,000/µL, or eGFR = 30 mL/min/1.73m2 using the Schwartz formula) (eculizumab-experienced participants or ravulizumab-experienced participants only), Known familial or acquired ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13”) deficiency (activity < 5%), Known Shiga toxin-related hemolytic uremic syndrome (ST-HUS) as demonstrated by a positive test for Shiga toxin or culture of Shiga toxin producing bacteria, Positive direct Coombs test which in the judgment of the Investigator is indicative of a clinically significant immune-mediated hemolysis not due to TMA, History of unexplained infections, Participants with a confirmed di
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method