Open-label, Multiple Ascending Dose Study of Ravulizumab (ALXN1210) in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

NCT ID: NCT02605993

Last Updated: 2023-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-04
• Study Completion Date: 2022-01-12

Brief Summary

The primary purpose of this study is to evaluate the safety, tolerability, and efficacy of multiple intravenous (IV) doses of ravulizumab administered to complement inhibitor treatment-naïve participants with PNH.

Detailed Description

The study consisted of a screening period of up to 30 days and a Treatment Period of up to 253 days for Cohorts 1-3 and 281 days for Cohort 4. After completion of the Treatment Period, all participants had the opportunity to enter the Extension Period, wherein participants continue to receive ravulizumab for up to 5 years. The first dose in the Extension Period occurred on Day 253 for Cohorts 1-3 and on Day 281 for Cohort 4.

The data presented includes the Primary Completion date of the study for the Treatment Period. The results for the Extension Period will be reported after study completion.

Conditions

Paroxysmal Nocturnal Hemoglobinuria; PNH

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

During the Treatment Period, participants were administered ravulizumab 1400 milligram (mg) on Day 1, ravulizumab 1000 mg on Day 15 and Day 29, and then ravulizumab 1000 mg every 4 weeks for 7 doses.

In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kilograms (kg), 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: BIOLOGICAL

All treatments were given as IV infusions.

Cohort 2

During the Treatment Period, participants were administered ravulizumab 2000 mg on Day 1, ravulizumab 1600 mg on Day 22 and Day 43, and then ravulizumab 1600 mg every 6 weeks for 4 doses.

In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: BIOLOGICAL

All treatments were given as IV infusions.

Cohort 3

During the Treatment Period, participants were administered ravulizumab 1600 mg on Day 1 and Day 15, ravulizumab 2400 mg on Day 29, and then ravulizumab 2400 mg every 8 weeks for 3 doses.

In the Extension Period, participants initially continued to receive their dose. During the second year of the study, participants were administered weight-based doses of ravulizumab every 8 weeks for up to 5 years: 3000 mg for participants weighing 40 to less than 60 kg, 3300 mg for participants weighing 60 to less than 100 kg, and 3600 mg for participants weighing 100 kg or more.

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: BIOLOGICAL

All treatments were given as IV infusions.

Cohort 4

During the Treatment Period, participants were administered ravulizumab 3000 mg on Day 1, ravulizumab 5400 mg on Day 29, and then ravulizumab 5400 mg every 12 weeks for 2 doses.

During the Extension Period, participants were administered ravulizumab 5400 mg every 12 weeks for up to 5 years.

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: BIOLOGICAL

All treatments were given as IV infusions.

Interventions

Ravulizumab

All treatments were given as IV infusions.

Intervention Type: BIOLOGICAL

Other Intervention Names

ALXN1210; Ultomiris

Eligibility Criteria

Inclusion Criteria

1. Male or female ≥18 years of age

2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry

3. Documented meningococcal vaccination not more than 3 years prior to dosing

4. Female participants of childbearing potential were to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

5. Willing and able to give written informed consent and comply with the study visit schedule

Exclusion Criteria

1. Treatment with a complement inhibitor at any time

2. Female participants who are planning to become pregnant, or are pregnant, breastfeeding or who had a positive pregnancy test at screening or Day 1

3. Participation in an interventional clinical study within 30 days before initiation of dosing on Day 1, or use of any experimental therapy within 30 days prior to dosing on Day 1, or within 5 half-lives of the investigational product, whichever was greater

4. History of allergy to any drug, allergen, excipients of ravulizumab or known allergy to Chinese hamster ovary cell proteins

5. Inability to comply with study requirements

6. History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, in the Investigator's judgment, would preclude participation

7. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the participant unsuitable for enrollment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Clinical Trial Site

Toronto, Ontario, Canada

Clinical Trial Site

Lyon, Pierre-Bénite, France

Clinical Trial Site

Lille, , France

Clinical Trial Site

Paris, , France

Clinical Trial Site

Ulm, Baden-Wurttemberg, Germany

Clinical Trial Site

Aachen, North Rhine-Westphalia, Germany

Clinical Trial Site

Essen, North Rhine-Westphalia, Germany

Clinical Trial Site

Seoul, , South Korea

Clinical Trial Site

Seoul, , South Korea

Clinical Trial Site

Badalona, Barcelona, Spain

Clinical Trial Site

Majadahonda, Madrid, Spain

Clinical Trial Site

Barcelona, , Spain

Clinical Trial Site

Madrid, , Spain

Clinical Trial Site

Taipei, , Taiwan

Clinical Trial Site

Leeds, West Yorkshire, United Kingdom

Clinical Trial Site

London, , United Kingdom

Countries

Canada; France; Germany; South Korea; Spain; Taiwan; United Kingdom

References

Roth A, Rottinghaus ST, Hill A, Bachman ES, Kim JS, Schrezenmeier H, Terriou L, Urbano-Ispizua A, Wells RA, Jang JH, Kulasekararaj AG, Szer J, Aguzzi R, Damokosh AI, Shafner L, Lee JW. Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies. Blood Adv. 2018 Sep 11;2(17):2176-2185. doi: 10.1182/bloodadvances.2018020644.

Reference Type: DERIVED

PMID: 30171081 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-002674-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALXN1210-PNH-201

Identifier Type: -

Identifier Source: org_study_id