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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02598583
Recruitment Status : Completed
First Posted : November 6, 2015
Results First Posted : January 30, 2018
Last Update Posted : May 16, 2022
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

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.

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

Detailed Description:
The data presented is up to the Primary Completion date of the study and is for the 24-week Primary Evaluation period. The study also includes an Extension Period of up to 5 years.

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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 12, 2015
Actual Primary Completion Date : July 14, 2016
Actual Study Completion Date : March 11, 2021


Arm Intervention/treatment
Experimental: Cohort 1

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

Experimental: Cohort 2

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




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 And Day 1821 [ Time Frame: Baseline, Day 169, Day 1821 ]
    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 And Day 1821 [ Time Frame: Baseline, Day 169, Day 1821 ]
    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 And Day 1821 [ Time Frame: Baseline, Day 169, Day 1821 ]
    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 And Day 1933 [ Time Frame: Baseline, Day 169, Day 1933 ]
    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 And Day 1821 [ Time Frame: Baseline, Day 169, Day 1821 ]
    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 And Day 1821 [ Time Frame: Baseline, Day 169, Day 1821 ]
    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.

  7. Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1 [ Time Frame: Day 1 ]
    AUCt reported in hours*microgram/milliliter (h*ug/mL).

  8. AUCt/ Dose-normalized (D) At Day 1 [ Time Frame: Day 1 ]
  9. Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141 [ Time Frame: Day 141 ]
  10. AUCtau/D At Day 141 [ Time Frame: Day 141 ]
  11. Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141 [ Time Frame: Day 1 and Day 141 ]
  12. Cmax/D At Day 1 And Day 141 [ Time Frame: Day 1 and Day 141 ]
  13. Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141 [ Time Frame: Day 1 and Day 141 ]
  14. Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141 [ Time Frame: Day 1 and Day 141 ]
  15. Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709 [ Time Frame: Baseline, Day 1709 ]
  16. Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709 [ Time Frame: Baseline, Day 1709 ]
  17. Percent Change In Total C5 Concentration From Baseline To Day 1709 [ Time Frame: Baseline, Day 1709 ]
  18. Participants Experiencing Antidrug Antibodies (ADAs) [ Time Frame: Day 1821 ]


Information from the National Library of Medicine

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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 used highly effective contraception starting at screening and continuing until at least 24-weeks 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 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 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, made 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
Korea, Republic of
Clinical Trial Site
Seoul, Korea, Republic of, 03080
Clinical Trial Site
Seoul, Korea, Republic of, 03722
Clinical Trial Site
Seoul, Korea, Republic of, 05505
Clinical Trial Site
Seoul, Korea, Republic of, 06351
Clinical Trial Site
Seoul, Korea, Republic of, 06951
Clinical Trial Site
Ulsan, Korea, Republic of, 44033
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    
Other Study ID Numbers: ALXN1210-PNH-103
First Posted: November 6, 2015    Key Record Dates
Results First Posted: January 30, 2018
Last Update Posted: May 16, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
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
Anemia, Hemolytic
Anemia
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases
Ravulizumab
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs