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

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ClinicalTrials.gov Identifier: NCT02598583
Recruitment Status : Active, not recruiting
First Posted : November 6, 2015
Results First Posted : January 30, 2018
Last Update Posted : June 4, 2019
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
This study is evaluating 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.

Condition or disease Intervention/treatment Phase
PNH Biological: ALXN1210 Phase 1 Phase 2

Detailed Description:
This study is ongoing. The data presented is up to the Primary Completion date of the study and is for the Primary Evaluation period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Intrapatient, Dose-Escalation Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients With Paroxysmal Nocturnal Hemoglobinuria
Actual Study Start Date : November 2015
Actual Primary Completion Date : July 2016
Estimated Study Completion Date : June 2021


Arm Intervention/treatment
Experimental: Cohort 1

Intravenous infusion of ALXN1210 as follows:

Induction phase: a) 400 milligrams (mg) on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

On Day 477, the dose and dosing interval for all participants changed to an every-8-week, weight-based regimen as follows:

  • ≥40 to <60 kilograms (kg): 3000 mg every 8 weeks
  • ≥60 to <100 kg: 3300 mg every 8 weeks
  • ≥100 kg: 3600 mg every 8 weeks
Biological: ALXN1210
Experimental: Cohort 2

Intravenous infusion of ALXN1210 as follows:

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

On Day 477, the dose and dosing interval for all participants changed to an every-8-week, weight-based regimen as follows:

  • ≥40 to <60 kg: 3000 mg every 8 weeks
  • ≥60 to <100 kg: 3300 mg every 8 weeks
  • ≥100 kg: 3600 mg every 8 weeks
Biological: ALXN1210



Primary Outcome Measures :
  1. Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169 [ Time Frame: Baseline, Day 169 ]
    Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.


Secondary Outcome Measures :
  1. Percent Change In Free Hemoglobin Levels From Baseline To Day 169 [ Time Frame: Baseline, Day 169 ]
    Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.

  2. Percent Change In Haptoglobin Levels From Baseline To Day 169 [ Time Frame: Baseline, Day 169 ]
    Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.

  3. Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 [ Time Frame: Baseline, Day 169 ]
    Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.

  4. Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 [ Time Frame: Baseline, Day 169 ]
    Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.

  5. Percent Change In D-dimer Levels From Baseline To Day 169 [ Time Frame: Baseline, Day 169 ]
    Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.

  6. Change In Clinical Manifestations Of PNH From Baseline To Day 169 [ Time Frame: Baseline, Day 169 ]
    Clinical manifestations are defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (ED) by cohort. Improvement is defined as present at baseline and absent at Day 169 endpoint. Worsening is defined as absent at Baseline and present at Day 169 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 patients of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ALXN1210
  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 are pregnant, breastfeeding or who have 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 product, whichever is greater
  4. History of allergy to excipients of ALXN1210 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): NCT02598583


Locations
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Australia, New South Wales
Clinical Trial Site
Liverpool, New South Wales, Australia, 2170
Australia, Queensland
Clinical Trial Site
Woolloongabba, Queensland, Australia, 4102
Australia, Victoria
Clinical Trial Site
Parkville, Victoria, Australia, 6150
Korea, Republic of
Clinical Trial Site
Daejeon, Korea, Republic of, 301-721
Clinical Trial Site
Seoul, Korea, Republic of, 03080
Clinical Trial Site
Seoul, Korea, Republic of, 120-752
Clinical Trial Site
Seoul, Korea, Republic of, 135-710
Clinical Trial Site
Seoul, Korea, Republic of, 137-701
Clinical Trial Site
Seoul, Korea, Republic of, 138-736
Clinical Trial Site
Ulsan, Korea, Republic of, 682-714
Sponsors and Collaborators
Alexion Pharmaceuticals
Investigators
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Study Director: Alexion Pharmaceuticals, Inc. Alexion Pharmaceuticals

Additional Information:
Publications:
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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02598583     History of Changes
Other Study ID Numbers: ALXN1210-PNH-103
First Posted: November 6, 2015    Key Record Dates
Results First Posted: January 30, 2018
Last Update Posted: June 4, 2019
Last Verified: May 2019
Keywords provided by Alexion Pharmaceuticals:
Paroxysmal Nocturnal Hemoglobinuria
PNH
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