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ALXN1210 Versus Eculizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab

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ClinicalTrials.gov Identifier: NCT03056040
Recruitment Status : Active, not recruiting
First Posted : February 16, 2017
Results First Posted : March 21, 2019
Last Update Posted : May 16, 2019
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult participants with PNH who were clinically stable after having been treated with eculizumab for at least 6 months.

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria (PNH) Biological: Ravulizumab Biological: Eculizumab Phase 3

Detailed Description:

The study consisted of a 4-week Screening Period and a 26-week Randomized Treatment Period (Primary Evaluation Period). After completion of the Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants will receive ravulizumab for up to 3 years.

This study is ongoing. The data presented is up to the Primary Completion date of the study and is for the Primary Evaluation Period. The results for the Extension Period will be reported after study completion.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 195 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab
Actual Study Start Date : June 5, 2017
Actual Primary Completion Date : March 8, 2018
Estimated Study Completion Date : March 2021


Arm Intervention/treatment
Experimental: Ravulizumab

On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 milligrams (mg). Thereafter, weight-based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127.

After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 3 years.

Biological: Ravulizumab
All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to <60 kilograms (kg): 2400 mg was given as a single loading dose, followed by 3000 mg as maintenance dose. For participants weighing ≥60 to <100 kg: 2700 mg was given as a loading dose, followed by 3300 mg as maintenance dose. For participants weighing ≥100 kg: 3000 mg was given as a loading dose, followed by 3600 mg as maintenance dose.
Other Names:
  • ALXN1210
  • ULTOMIRIS

Active Comparator: Eculizumab

Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks.

After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants will receive weight-based doses of ravulizumab for up to 3 years.

Biological: Ravulizumab
All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to <60 kilograms (kg): 2400 mg was given as a single loading dose, followed by 3000 mg as maintenance dose. For participants weighing ≥60 to <100 kg: 2700 mg was given as a loading dose, followed by 3300 mg as maintenance dose. For participants weighing ≥100 kg: 3000 mg was given as a loading dose, followed by 3600 mg as maintenance dose.
Other Names:
  • ALXN1210
  • ULTOMIRIS

Biological: Eculizumab
All treatments were given as IV infusions. Participants received 900 mg of eculizumab q2w.




Primary Outcome Measures :
  1. Percent Change In Lactate Dehydrogenase Levels From Baseline To Day 183 [ Time Frame: Baseline, Day 183 ]
    Lactate dehydrogenase (LDH) is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria. A decrease in LDH indicates reduction (improvement) in hemolysis. Baseline was defined as the average of all available on-study assessments prior to the first study drug infusion. The percent change in LDH was analyzed using a mixed-effect model for repeated measures (MMRM) with the fixed, categorical effects of treatment, study visit, and study visit by treatment group interaction, as well as the continuous, fixed covariate of baseline LDH and the stratification randomization indicator of packed red blood cells transfusion history (yes/no within 12 months prior to Day 1).


Secondary Outcome Measures :
  1. Percentage Of Participants With Breakthrough Hemolysis [ Time Frame: Baseline through Day 183 ]
    Breakthrough hemolysis (BTH) was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia [hemoglobin <10 grams (g)/deciliter (dL)], major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 times the upper limit of normal (ULN).

  2. Change From Baseline To Day 183 In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scores [ Time Frame: Baseline, Day 183 ]
    FACIT-Fatigue score ranges from 0 to 52, with a higher score indicating less fatigue. Baseline was defined as the last non-missing assessment value prior to first study drug dose. Change in FACIT-Fatigue score from Baseline to Day 183 was analyzed using an MMRM with the fixed, categorical effects of treatment, the stratification randomization indicator of packed red blood cells transfusion history (yes/no within 12 months prior to Day 1), study visit, and study visit by treatment group interaction, as well as the continuous fixed covariate of Baseline FACIT-Fatigue score.

  3. Percentage Of Participants Who Achieved Transfusion Avoidance [ Time Frame: Baseline through Day 183 ]
    Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines (hemoglobin value of ≤9 g/dL with signs or symptoms of sufficient severity to warrant a transfusion, or a hemoglobin value of ≤7 g/dL regardless of presence of clinical signs or symptoms) through Day 183.

  4. Percentage Of Participants With Stabilized Hemoglobin Levels [ Time Frame: Baseline through Day 183 ]
    Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline in the absence of transfusion through Day 183.



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. Treated with eculizumab for PNH for at least 6 months prior to Day 1.
  3. Lactate dehydrogenase level ≤1.5 times the upper limit of normal (ULN) at screening.
  4. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.
  5. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
  6. Female participants of childbearing potential must use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.
  7. Willing and able to give written informed consent and comply with study visit schedule.

Exclusion Criteria:

  1. History of bone marrow transplantation.
  2. Body weight <40 kilograms at screening.
  3. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation.
  4. Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleeding, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, or coexisting chronic anemia unrelated to PNH).
  5. Female participants who are pregnant, breastfeeding, or who have a positive pregnancy test at screening or Day 1.
  6. Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study treatment on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.

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): NCT03056040


  Show 49 Study Locations
Sponsors and Collaborators
Alexion Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Alexion Pharmaceuticals:
Statistical Analysis Plan  [PDF] December 12, 2017
Study Protocol  [PDF] March 1, 2019


Publications:
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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03056040     History of Changes
Other Study ID Numbers: ALXN1210-PNH-302
2016-002026-36 ( EudraCT Number )
First Posted: February 16, 2017    Key Record Dates
Results First Posted: March 21, 2019
Last Update Posted: May 16, 2019
Last Verified: May 2019

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