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

Paroxysmal Nocturnal Hemoglobinuria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04320602
• Other study ID #: ALXN1210-PNH-401
• Secondary ID: 2019-003440-74
• Status: Completed
• Phase: Phase 4
• Start date: March 26, 2021
• Est. completion date: December 20, 2022

Study information

• Verified date: January 2023
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 20, 2022
• Est. primary completion date: December 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Paroxysmal Nocturnal Hemoglobinuria

Intervention

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.
• 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.

Locations

Country	Name	City	State
United Kingdom	Clinical Study Site	Leeds
United Kingdom	Clinical Study Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion Of Participants Who Experience Free Complement Component 5 (C5)-associated Breakthrough Hemolysis (BTH)		Baseline through Day 351
Secondary	Proportion Of Participants Who Experience BTH		Baseline through Day 351
Secondary	Hemolysis As Directly Measured By Lactate Dehydrogenase (LDH) Percent Change From Baseline To Day 351		Baseline, Day 351
Secondary	Proportion Of Participants Who Receive A Transfusion		Baseline through Day 351
Secondary	Proportion Of Participants With Stabilized Hemoglobin		Baseline through Day 351