Dose-Escalation Study of ALXN1210 IV in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

NCT02598583 | Completed Phase 1 Results DMC

• 1 other identifier: ALXN1210-PNH-103
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 8

Brief Summary

This study evaluated the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of multiple intravenous (IV) doses of ALXN1210 administered to participants with PNH who have not previously been treated with complement inhibitor.

Conditions

PNH

Keywords

Paroxysmal Nocturnal Hemoglobinuria; PNH; complement inhibitor

Outcome Measures

Primary Outcomes (1)

• Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169

  Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.

  Baseline, Day 169

Secondary Outcomes (18)

• Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821

  Baseline, Day 169, Day 1821

• Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821

  Baseline, Day 169, Day 1821

• Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821

  Baseline, Day 169, Day 1821

• Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933

  Baseline, Day 169, Day 1933

• Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821

  Baseline, Day 169, Day 1821

Study Arms (2)

Cohort 1

EXPERIMENTAL

Participants were administered ALXN1210 900 mg. In the Extension period participants continued at the same dose and frequency as the Primary Evaluation Period.

Biological: ALXN1210

Cohort 2

EXPERIMENTAL

Participants were administered ALXN1210 1800 mg. In the Extension period participants continued at the same dose and frequency as the Primary Evaluation Period.

Biological: ALXN1210

Interventions

ALXN1210 BIOLOGICAL

Participants were administered ravulizumab as an IV infusion every 4 weeks.

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years of age
• PNH diagnosis confirmed by documented high-sensitivity flow cytometry
• Documented meningococcal vaccination not more than 3 years prior to dosing
• Female participants of childbearing potential used highly effective contraception starting at screening and continuing until at least 24-weeks after the last dose of ALXN1210
• Willing and able to give written informed consent and comply with the study visit schedule

You may not qualify if:

• Treatment with a complement inhibitor at any time
• Females who were pregnant, breastfeeding or who had a positive pregnancy test at screening or Day 1
• 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 product, whichever is greater
• History of allergy to excipients of ALXN1210 or known allergy to Chinese hamster ovary cell proteins
• Inability to comply with study requirements
• History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, in the Investigator's judgment, would preclude participation
• Other unspecified reasons that, in the opinion of the Investigator or Sponsor, made the participant unsuitable for enrollment

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (8)

Clinical Trial Site

Liverpool, New South Wales, 2170, Australia

Location

Clinical Trial Site

Woolloongabba, Queensland, 4102, Australia

Location

Clinical Trial Site

Seoul, 03080, South Korea

Location

Clinical Trial Site

Seoul, 03722, South Korea

Location

Clinical Trial Site

Seoul, 05505, South Korea

Location

Clinical Trial Site

Seoul, 06351, South Korea

Location

Clinical Trial Site

Seoul, 06951, South Korea

Location

Clinical Trial Site

Ulsan, 44033, South Korea

Location

Related Publications (1)

• 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.

  PMID: 30171081 BACKGROUND

Related Links

• Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

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

+1 855-752-2356

Study Officials

• Alexion Pharmaceuticals, Inc.

  Alexion Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2015
• First Posted: November 6, 2015
• Study Start: November 12, 2015
• Primary Completion: July 14, 2016
• Study Completion: March 11, 2021
• Last Updated: May 16, 2022
• Results First Posted: January 30, 2018

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR

Locations

KR (6); AU (2)