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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03056040




Registration number
NCT03056040
Ethics application status
Date submitted
14/02/2017
Date registered
16/02/2017
Date last updated
16/05/2019

Titles & IDs
Public title
ALXN1210 Versus Eculizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab
Scientific 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
Secondary ID [1] 0 0
2016-002026-36
Secondary ID [2] 0 0
ALXN1210-PNH-302
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria (PNH) 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Ravulizumab
Other interventions - Eculizumab

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.

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.


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

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Change In Lactate Dehydrogenase Levels From Baseline To 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).
Timepoint [1] 0 0
Baseline, Day 183
Secondary outcome [1] 0 0
Percentage Of Participants With Breakthrough Hemolysis - 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).
Timepoint [1] 0 0
Baseline through Day 183
Secondary outcome [2] 0 0
Change From Baseline To Day 183 In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scores - 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.
Timepoint [2] 0 0
Baseline, Day 183
Secondary outcome [3] 0 0
Percentage Of Participants Who Achieved Transfusion Avoidance - 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.
Timepoint [3] 0 0
Baseline through Day 183
Secondary outcome [4] 0 0
Percentage Of Participants With Stabilized Hemoglobin Levels - 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.
Timepoint [4] 0 0
Baseline through Day 183

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,VIC
Recruitment hospital [1] 0 0
Clinical Trial Site - Canberra
Recruitment hospital [2] 0 0
Clinical Trial Site - Kogarah
Recruitment hospital [3] 0 0
Clinical Trial Site - Liverpool
Recruitment hospital [4] 0 0
Clinical Trial Site - Woolloongabba
Recruitment hospital [5] 0 0
Clinical Trial Site - Parkville
Recruitment postcode(s) [1] 0 0
2605 - Canberra
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Maryland
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United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
France
State/province [7] 0 0
Amiens
Country [8] 0 0
France
State/province [8] 0 0
Marseille
Country [9] 0 0
France
State/province [9] 0 0
Paris
Country [10] 0 0
France
State/province [10] 0 0
Pierre-Bénite
Country [11] 0 0
France
State/province [11] 0 0
Saint-Priest-en-Jarez
Country [12] 0 0
France
State/province [12] 0 0
Strasbourg
Country [13] 0 0
Germany
State/province [13] 0 0
Baden Wuerttemberg
Country [14] 0 0
Germany
State/province [14] 0 0
Nordrhein Westfalen
Country [15] 0 0
Italy
State/province [15] 0 0
Firenze
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Italy
State/province [17] 0 0
Napoli
Country [18] 0 0
Italy
State/province [18] 0 0
Torino
Country [19] 0 0
Italy
State/province [19] 0 0
Vicenza
Country [20] 0 0
Japan
State/province [20] 0 0
Ishikawa
Country [21] 0 0
Japan
State/province [21] 0 0
Nagano
Country [22] 0 0
Japan
State/province [22] 0 0
Osaka
Country [23] 0 0
Japan
State/province [23] 0 0
Tokyo
Country [24] 0 0
Japan
State/province [24] 0 0
Fukushima
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Daegu
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Daejeon
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Gyeonggi-do
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Incheon
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Seoul
Country [30] 0 0
Netherlands
State/province [30] 0 0
Maastricht
Country [31] 0 0
Netherlands
State/province [31] 0 0
Nijmegen
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
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Spain
State/province [34] 0 0
Majadahonda
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Airdrie
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Leeds
Country [37] 0 0
United Kingdom
State/province [37] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alexion Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03056040
Trial related presentations / publications
Kulasekararaj AG, Hill A, Rottinghaus ST, Langemeijer S, Wells R, Gonzalez-Fernandez FA, Gaya A, Lee JW, Gutierrez EO, Piatek CI, Szer J, Risitano A, Nakao S, Bachman E, Shafner L, Damokosh AI, Ortiz S, Röth A, Peffault de Latour R. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019 Feb 7;133(6):540-549. doi: 10.1182/blood-2018-09-876805. Epub 2018 Dec 3.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications