Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab

Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab

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).

Study Overview

• Status: Completed
• Conditions: Paroxysmal Nocturnal Hemoglobinuria
• Intervention / Treatment: Biological: Eculizumab; Biological: Ravulizumab

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Research Site
  • Leeds, United Kingdom, LS9 7TF
    • Clinical Study Site
  • London, United Kingdom, SE5 9RS
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ravulizumab; Participants will receive eculizumab during the 3-month Screening Period. Participants will then switch over to and receive weight-based doses of ravulizumab for the duration of the study Treatment Period (351 days).

Biological: Eculizumab; Participants must have been prescribed and be receiving a stable dose of eculizumab 1200 milligrams (mg) every 2 weeks (q2w) for at least 3 months prior to the Screening Period. During the Screening Period, participants will continue to receive eculizumab 1200 mg q2w.; Other Names: Soliris; Biological: Ravulizumab; During the Treatment Period, participants will receive a loading dose of ravulizumab on Day 1, followed by maintenance doses on Day 15 and every 8 weeks, administered by intravenous infusion. Ravulizumab loading and maintenance doses will be based on participants' body weight per approved dose regimen.; Other Names: Ultomiris; ALXN1210

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced Free C5-associated BTH	Free C5-associated BTH was defined as BTH concurrent with free C5 concentrations ≥0.5 micrograms (μg)/milliliter (mL). BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 grams {g}/deciliter {dL}], major adverse vascular event [MAVE], including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated lactate dehydrogenase (LDH) ≥2 * upper limit of normal (ULN).	Baseline through Day 351

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced BTH	BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath [dyspnea], anemia [hemoglobin <10 g/dL], MAVE, including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 * ULN.	Baseline through Day 351
Percent Change From Baseline in LDH at Day 351		Baseline, Day 351
Percentage of Participants Who Received a Red Blood Cell (RBC) Transfusion		Baseline through Day 351
Percentage of Participants With Stabilized Hemoglobin	Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline in the absence of transfusion from Baseline to Day 351.	Baseline through Day 351

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2021
• Primary Completion (Actual): December 20, 2022
• Study Completion (Actual): December 20, 2022

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 23, 2020
• First Posted (Actual): March 25, 2020

Study Record Updates

• Last Update Posted (Estimated): September 5, 2024
• Last Update Submitted That Met QC Criteria: August 12, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: PNH; Paroxysmal Nocturnal Hemoglobinuria; Eculizumab; Ravulizumab; Ultomiris; Soliris
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hemoglobinuria; Hemoglobinuria, Paroxysmal; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab; Ravulizumab
• Other Study ID Numbers: ALXN1210-PNH-401; 2019-003440-74 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No