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

NCT04320602 | Completed Phase 4 Results

• 2 other identifiers: ALXN1210-PNH-4012019-003440-74
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

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).

Conditions

Paroxysmal Nocturnal Hemoglobinuria

Keywords

Paroxysmal Nocturnal Hemoglobinuria; PNH; Ravulizumab; Ultomiris; Eculizumab; Soliris

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percentage of Participants Who Experienced BTH

  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

  Baseline through Day 351

Study Arms (1)

Ravulizumab

EXPERIMENTAL

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; Biological: Ravulizumab

Interventions

Eculizumab BIOLOGICAL

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.

Also known as: Soliris

Ravulizumab

Ravulizumab BIOLOGICAL

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.

Also known as: ALXN1210, Ultomiris

Ravulizumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.
• Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening.
• LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening.
• 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.
• Body weight ≥ 40 kilograms.

You may not qualify if:

• History of major adverse vascular events within 6 months of Day 1.
• History of bone marrow transplantation.
• 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.
• Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day 1.
• 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
• Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.
• More than 1 LDH value \> 2 × ULN within the 6 months prior to Day 1.
• Platelet count \< 30,000/cubic millimeter (30 × 10\^9/Liter \[L\]) at Screening.
• Absolute neutrophil count \< 500/microliter (0.5 × 10\^9/L) at Screening.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (4)

Clinical Study Site

Leeds, LS9 7TF, United Kingdom

Location

Research Site

Leeds, LS9 7TF, United Kingdom

Location

Clinical Study Site

London, SE5 9RS, United Kingdom

Location

Research Site

London, SE5 9RS, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

eculizumab; ravulizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: March 25, 2020
• Study Start: April 14, 2021
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: September 5, 2024
• Results First Posted: August 12, 2024

Record last verified: 2024-07

Locations

GB (4)