Clinical trial NCT04320602: Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
Official title: Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Keywords: Paroxysmal Nocturnal Hemoglobinuria
PNH
Ravulizumab
Ultomiris
Eculizumab
Soliris
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-25
Enrollment: 18
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab in participants who are prescribed and are receiving a higher than approved dose of eculizumab to treat paroxysmal nocturnal hemoglobinuria (PNH).


Eligibility criteria: Key Inclusion Criteria:

1. Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation of red blood cells and white blood cells, with granulocyte or monocyte clone size of ≥ 5%.
2. Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening.
3. LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening.
4. To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infections within 3 years prior to initiating study drug.
5. Body weight ≥ 40 kilograms.

Key Exclusion Criteria:

1. History of major adverse vascular events within 6 months of Day 1.
2. History of bone marrow transplantation.
3. Lymphoma, leukemia, myelodysplastic syndrome, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
4. Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.
5. Concomitant use of any of the following medications and not on a stable regimen (as judged by the Investigator) for the time period indicated prior to Screening:

   * Erythropoietin or immunosuppressants for at least 8 weeks
   * Systemic corticosteroids for at least 4 weeks
   * Vitamin K antagonists (for example, warfarin) with a stable international normalized ratio level for at least 4 weeks
   * Iron supplements or folic acid for 4 weeks
6. Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.
7. More than 1 LDH value \> 2 × ULN within the 6 months prior to Day 1.
8. Platelet count \< 30,000/cubic millimeter (30 × 10\^9/Liter \[L\]) at Screening.
9. Absolute neutrophil count \< 500/microliter (0.5 × 10\^9/L) at Screening.

Primary outcomes:
measure: Percentage of Participants Who Experienced Free C5-associated BTH
timeFrame: Baseline through Day 351
Secondary outcomes:
measure: Percentage of Participants Who Experienced BTH
timeFrame: Baseline through Day 351
measure: Percent Change From Baseline in LDH at Day 351
timeFrame: Baseline, Day 351
measure: Percentage of Participants Who Received a Red Blood Cell (RBC) Transfusion
timeFrame: Baseline through Day 351
measure: Percentage of Participants With Stabilized Hemoglobin
timeFrame: Baseline through Day 351
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Clinical Study Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Clinical Study Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
References: