NCT02605993

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
26

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2016

Longer than P75 for phase_2

Geographic Reach
7 countries

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 11, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

November 17, 2015

Completed
2 months until next milestone

Study Start

First participant enrolled

January 4, 2016

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 23, 2017

Completed
2 years until next milestone

Results Posted

Study results publicly available

February 18, 2019

Completed
2.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 12, 2022

Completed
Last Updated

January 4, 2023

Status Verified

December 1, 2022

Enrollment Period

1.1 years

First QC Date

November 11, 2015

Results QC Date

January 18, 2019

Last Update Submit

December 7, 2022

Conditions

Paroxysmal Nocturnal HemoglobinuriaPNH

Keywords

complement inhibitor

Outcome Measures

Primary Outcomes (1)

  • Percent Change In LDH Levels From Baseline To Day 253 And Day 281

    The percent change in LDH levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.

    Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)

Secondary Outcomes (6)

  • Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281

    Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)

  • Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281

    Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)

  • Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281

    Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)

  • Percent Change In PNH RBC Types II And III Clone Size From Baseline To Day 253

    Baseline, Day 253 (Cohorts 1 to 4)

  • Percent Change In D-dimer From Baseline To Day 253 And Day 281

    Baseline to Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4)

  • +1 more secondary outcomes

Study Arms (4)

Cohort 1

EXPERIMENTAL

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.

Biological: Ravulizumab

Cohort 2

EXPERIMENTAL

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.

Biological: Ravulizumab

Cohort 3

EXPERIMENTAL

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.

Biological: Ravulizumab

Cohort 4

EXPERIMENTAL

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.

Biological: Ravulizumab

Interventions

RavulizumabBIOLOGICAL

All treatments were given as IV infusions.

Also known as: ALXN1210, Ultomiris
Cohort 1Cohort 2Cohort 3Cohort 4

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (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 were to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
  • 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
  • Female participants who are planning to become pregnant, or are 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 investigational product, whichever was greater
  • History of allergy to any drug, allergen, excipients of ravulizumab 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, make the participant unsuitable for enrollment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Clinical Trial Site

Toronto, Ontario, M4N 3M5, Canada

Location

Clinical Trial Site

Lyon, Pierre-Bénite, 69495, France

Location

Clinical Trial Site

Lille, 59037, France

Location

Clinical Trial Site

Paris, 75475, France

Location

Clinical Trial Site

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Clinical Trial Site

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Clinical Trial Site

Essen, North Rhine-Westphalia, 45147, Germany

Location

Clinical Trial Site

Seoul, 03080, South Korea

Location

Clinical Trial Site

Seoul, 03722, South Korea

Location

Clinical Trial Site

Badalona, Barcelona, 08916, Spain

Location

Clinical Trial Site

Majadahonda, Madrid, 28220, Spain

Location

Clinical Trial Site

Barcelona, 08036, Spain

Location

Clinical Trial Site

Madrid, 28040, Spain

Location

Clinical Trial Site

Taipei, 10048, Taiwan

Location

Clinical Trial Site

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

Clinical Trial Site

London, SE5 9RS, United Kingdom

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: 30171081DERIVED

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

ravulizumab

Condition Hierarchy (Ancestors)

Anemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesMyelodysplastic SyndromesBone Marrow Diseases

Results Point of Contact

Title
Alexion Pharmaceuticals, Inc.
Organization
Alexion Pharmaceuticals, Inc.
clinicaltrials@alexion.com
+1-855-752-2356

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 11, 2015

First Posted

November 17, 2015

Study Start

January 4, 2016

Primary Completion

February 23, 2017

Study Completion

January 12, 2022

Last Updated

January 4, 2023

Results First Posted

February 18, 2019

Record last verified: 2022-12

Locations

TW(1)DE(3)FR(3)ES(4)GB(2)CA(1)KR(2)