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

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ClinicalTrials.gov Identifier: NCT02605993
Recruitment Status : Active, not recruiting
First Posted : November 17, 2015
Results First Posted : February 18, 2019
Last Update Posted : February 18, 2019
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria PNH Biological: Ravulizumab Phase 2

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.

This study is ongoing. 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label, Multiple Ascending Dose Study to Evaluate the Efficacy, Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients With Paroxysmal Nocturnal Hemoglobinuria
Actual Study Start Date : January 4, 2016
Actual Primary Completion Date : February 23, 2017
Estimated Study Completion Date : March 2022


Arm Intervention/treatment
Experimental: 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.

Biological: Ravulizumab
All treatments were given as IV infusions.
Other Names:
  • ALXN1210
  • Ultomiris

Experimental: 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.

Biological: Ravulizumab
All treatments were given as IV infusions.
Other Names:
  • ALXN1210
  • Ultomiris

Experimental: 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.

Biological: Ravulizumab
All treatments were given as IV infusions.
Other Names:
  • ALXN1210
  • Ultomiris

Experimental: 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.

Biological: Ravulizumab
All treatments were given as IV infusions.
Other Names:
  • ALXN1210
  • Ultomiris




Primary Outcome Measures :
  1. Percent Change In LDH Levels From Baseline To Day 253 And Day 281 [ Time Frame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) ]
    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.


Secondary Outcome Measures :
  1. Percent Change In Free Hemoglobin Levels From Baseline To Day 253 And Day 281 [ Time Frame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) ]
    The percent change in free hemoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.

  2. Percent Change In Haptoglobin Levels From Baseline To Day 253 And Day 281 [ Time Frame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) ]
    The percent change in haptoglobin levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.

  3. Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 253 And Day 281 [ Time Frame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) ]
    The percent change in reticulocyte/erythrocyte count levels was assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.

  4. Percent Change In PNH RBC Types II And III Clone Size From Baseline To Day 253 [ Time Frame: Baseline, Day 253 (Cohorts 1 to 4) ]
    The percent change in paroxysmal nocturnal hemoglobinuria (PNH) red blood cell (RBC), summed types II and III, clone size levels were assessed from Baseline to Day 253 for Cohorts 1 to 4.

  5. Percent Change In D-dimer From Baseline To Day 253 And Day 281 [ Time Frame: Baseline to Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) ]
    The percent change in D-dimer levels were assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only.

  6. Change In Clinical Manifestations Of PNH From Baseline To Day 253 And Day 281 [ Time Frame: Baseline, Day 253 (Cohorts 1 to 4) and Day 281 (Cohort 4) ]
    Clinical manifestations were assessed from Baseline to Day 253 for Cohorts 1 to 4 and from Baseline to Day 281 for Cohort 4 only. Clinical manifestations were defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (male participants only). Improvement was defined as present at Baseline and absent at Day endpoint. Worsening was defined as absent at Baseline and present at Day endpoint. No Change was defined as no change from Baseline and time point of endpoint.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Females who were 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02605993


Locations
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Canada, Alberta
Clinical Trial Site
Edmonton, Alberta, Canada, T6G 2B7
Canada, Ontario
Clinical Trial Site
Toronto, Ontario, Canada, M4N 3M5
Canada
Clinical Trial Site
Quebec, Canada, HIT 2M4
France
Clinical Trial Site
Lyon, Pierre-Bénite, France, 69310
Clinical Trial Site
Lille, France, 59037
Clinical Trial Site
Paris, France, 75475
Clinical Trial Site
Rennes, France, 35000
Germany
Clinical Trial Site
Ulm, Baden Wuerttemberg, Germany, 89081
Clinical Trial Site
Aachen, Nordrhein Westfalen, Germany, 52074
Clinical Trial Site
Essen, Nordrhein Westfalen, Germany, 45147
Clinical Trial Site
Hamburg, Germany, 20246
Korea, Republic of
Clinical Trial Site
Seoul, Korea, Republic of, 03080
Clinical Trial Site
Seoul, Korea, Republic of, 06351
Clinical Trial Site
Seoul, Korea, Republic of, 120-752
Clinical Trial Site
Seoul, Korea, Republic of, 137-701
Spain
Clinical Trial Site
Badalona, Barcelona, Spain, 08916
Clinical Trial Site
Majadahonda, Madrid, Spain, 28220
Clinical Trial Site
Barcelona, Spain, 08036
Clinical Trial Site
Madrid, Spain, 28040
Taiwan
Clinical Trial Site
Changhua, Taiwan, 500
Clinical Trial Site
Taipei City, Taiwan, 1002
United Kingdom
Clinical Trial Site
Airdrie, North Lanarkshire, United Kingdom, ML6 0JS
Clinical Trial Site
Leeds, West Yorkshire, United Kingdom, LS9 7TF
Clinical Trial Site
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Alexion Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Alexion Pharmaceuticals:
Study Protocol  [PDF] May 9, 2018
Statistical Analysis Plan  [PDF] June 29, 2016


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02605993     History of Changes
Other Study ID Numbers: ALXN1210-PNH-201
2015-002674-20 ( EudraCT Number )
First Posted: November 17, 2015    Key Record Dates
Results First Posted: February 18, 2019
Last Update Posted: February 18, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alexion Pharmaceuticals:
complement inhibitor

Additional relevant MeSH terms:
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Hemoglobinuria
Hemoglobinuria, Paroxysmal
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases
Ravulizumab
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs