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

NCT03056040 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: ALXN1210-PNH-3022016-002026-36
• Study Type: interventional
• Target: 202
• Locations: 11 countries
• Sites: 51

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline, Day 183

Secondary Outcomes (8)

• Number Of Participants With Breakthrough Hemolysis Through Day 183

  Baseline through Day 183

• Change From Baseline To Day 183 In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scores

  Baseline, Day 183

• Percentage Of Participants Who Achieved Transfusion Avoidance Through Day 183

  Baseline through Day 183

• Percentage Of Participants With Stabilized Hemoglobin Levels Through Day 183

  Baseline through Day 183

• Number Of Participants With Breakthrough Hemolysis Through End of Study

  Baseline through end of study (up to 4 years)

Study Arms (2)

Ravulizumab

EXPERIMENTAL

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 4 years.

Biological: Ravulizumab

Eculizumab

ACTIVE COMPARATOR

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 4 years.

Biological: Ravulizumab; Biological: Eculizumab

Interventions

Ravulizumab BIOLOGICAL

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.

Also known as: ALXN1210, ULTOMIRIS

Eculizumab; Ravulizumab

Eculizumab BIOLOGICAL

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

Eculizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥18 years of age.
• Treated with eculizumab for PNH for at least 6 months prior to Day 1.
• Lactate dehydrogenase level ≤1.5 times the upper limit of normal (ULN) at screening.
• PNH diagnosis confirmed by documented by high-sensitivity flow cytometry.
• Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study treatment.
• 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.
• Willing and able to give written informed consent and comply with study visit schedule.

You may not qualify if:

• History of bone marrow transplantation.
• Body weight \<40 kilograms at screening.
• History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation.
• 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).
• Female participants who are pregnant, breastfeeding, or who have a positive pregnancy test at screening or Day 1.
• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (51)

Research Site

Duarte, California, 91010, United States

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Los Angeles, California, 90089, United States

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Baltimore, Maryland, 21205, United States

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Detroit, Michigan, 48202, United States

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The Bronx, New York, 10467, United States

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Canberra, 2605, Australia

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Kogarah, 2217, Australia

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Liverpool, 2170, Australia

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Melbourne, 3000, Australia

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Woolloongabba, 4102, Australia

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5G 2C4, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Amiens, 80054, France

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La Tronche, 38043, France

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Marseille, 13273, France

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Nice, 06200, France

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Paris, 75475, France

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Pierre-Bénite, 69495, France

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Saint-Priest-en-Jarez, 42270, France

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Strasbourg, 67091, France

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Aachen, 52074, Germany

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Essen, 45147, Germany

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Ulm, 89081, Germany

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Florence, 50134, Italy

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Milan, 20122, Italy

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Napoli, 80131, Italy

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Torino, 10126, Italy

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Vicenza, 36100, Italy

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Fukushima, 960-1295, Japan

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Kanazawa, 920-8641, Japan

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Shinagawa-ku, 141-0022, Japan

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Suita-shi, 565-0871, Japan

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Suwa-shi, 392-8510, Japan

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Maastricht, 6202 AZ, Netherlands

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Nijmegen, 6525 GA, Netherlands

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Bucheon-si, 14584, South Korea

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Daegu, 42415, South Korea

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Daejeon, 35015, South Korea

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Incheon, 21565, South Korea

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Seoul, 03080, South Korea

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Seoul, 06351, South Korea

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Seoul, 3722, South Korea

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Seoul, 6591, South Korea

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Suwon, 16247, South Korea

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Barcelona, 8036, Spain

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Madrid, 28040, Spain

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Majadahonda, 28220, Spain

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Airdrie, ML6 0JS, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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London, SE5 9NU, United Kingdom

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Related Publications (10)

• 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, Roth 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.

  PMID: 30510079 BACKGROUND

• Brodsky RA, Peffault de Latour R, Rottinghaus ST, Roth A, Risitano AM, Weitz IC, Hillmen P, Maciejewski JP, Szer J, Lee JW, Kulasekararaj AG, Volles L, Damokosh AI, Ortiz S, Shafner L, Liu P, Hill A, Schrezenmeier H. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Jan 1;106(1):230-237. doi: 10.3324/haematol.2019.236877.

  PMID: 31949012 BACKGROUND

• Ishiyama K, Nakao S, Usuki K, Yonemura Y, Ikezoe T, Uchiyama M, Mori Y, Fukuda T, Okada M, Fujiwara SI, Noji H, Rottinghaus S, Aguzzi R, Yokosawa J, Nishimura JI, Kanakura Y, Okamoto S. Results from multinational phase 3 studies of ravulizumab (ALXN1210) versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria: subgroup analysis of Japanese patients. Int J Hematol. 2020 Oct;112(4):466-476. doi: 10.1007/s12185-020-02934-6. Epub 2020 Aug 31.

  PMID: 32869125 BACKGROUND

• Kulasekararaj AG, Griffin M, Langemeijer S, Usuki K, Kulagin A, Ogawa M, Yu J, Mujeebuddin A, Nishimura JI, Lee JW, Peffault de Latour R; 301/302 Study Group. Long-term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2-year results from two pivotal phase 3 studies. Eur J Haematol. 2022 Sep;109(3):205-214. doi: 10.1111/ejh.13783. Epub 2022 Jun 16.

  PMID: 35502600 BACKGROUND

• Kulasekararaj AG, Hill A, Langemeijer S, Wells R, Gonzalez Fernandez FA, Gaya A, Ojeda Gutierrez E, Piatek CI, Mitchell L, Usuki K, Bosi A, Brodsky RA, Ogawa M, Yu J, Ortiz S, Roth A, Lee JW, Peffault de Latour R. One-year outcomes from a phase 3 randomized trial of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria who received prior eculizumab. Eur J Haematol. 2021 Mar;106(3):389-397. doi: 10.1111/ejh.13564. Epub 2021 Jan 3.

  PMID: 33301613 BACKGROUND

• Peffault de Latour R, Brodsky RA, Ortiz S, Risitano AM, Jang JH, Hillmen P, Kulagin AD, Kulasekararaj AG, Rottinghaus ST, Aguzzi R, Gao X, Wells RA, Szer J. Pharmacokinetic and pharmacodynamic effects of ravulizumab and eculizumab on complement component 5 in adults with paroxysmal nocturnal haemoglobinuria: results of two phase 3 randomised, multicentre studies. Br J Haematol. 2020 Nov;191(3):476-485. doi: 10.1111/bjh.16711. Epub 2020 May 24.

  PMID: 32449174 BACKGROUND

• Schrezenmeier H, Kulasekararaj A, Mitchell L, Sicre de Fontbrune F, Devos T, Okamoto S, Wells R, Rottinghaus ST, Liu P, Ortiz S, Lee JW, Socie G. One-year efficacy and safety of ravulizumab in adults with paroxysmal nocturnal hemoglobinuria naive to complement inhibitor therapy: open-label extension of a randomized study. Ther Adv Hematol. 2020 Oct 24;11:2040620720966137. doi: 10.1177/2040620720966137. eCollection 2020.

  PMID: 33178408 BACKGROUND

• Wietz IC, Kulagin A, Nakao S, Piatek CI, Szer J, Rottinghaus ST, Volles L, Damokosh AI, Aguzzi R, Larratt L, Risitano AM. A Phase 3 study of ravulizumab (ALXN1210) versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria naive to complement inhibitors: results of a subgroup analysis with patients stratified by baseline hemolysis level, transfusion history, and demographics. Blood. 2018;132 (Supplement 1):627. doi: 10.1182/blood-2018-99-110623

  BACKGROUND

• Kulasekararaj A, Brodsky R, Schrezenmeier H, Griffin M, Roth A, Piatek C, Ogawa M, Yu J, Patel AS, Patel Y, Notaro R, Usuki K, Kulagin A, Gualandro S, Fureder W, Peffault de Latour R, Szer J, Lee JW. Ravulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria. Ann Hematol. 2025 Jan;104(1):81-94. doi: 10.1007/s00277-025-06193-5. Epub 2025 Jan 22.

  PMID: 39841198 DERIVED

• Schwartz CE, Stark RB, Borowiec K, Nolte S, Myren KJ. Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. Orphanet J Rare Dis. 2021 Sep 15;16(1):389. doi: 10.1186/s13023-021-02016-8.

  PMID: 34526067 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

ravulizumab; eculizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2017
• First Posted: February 16, 2017
• Study Start: May 17, 2017
• Primary Completion: February 21, 2022
• Study Completion: February 21, 2022
• Last Updated: March 12, 2025
• Results First Posted: March 21, 2019

Record last verified: 2025-02

Locations

NL (2); ES (3); DE (3); KR (9); AU (5); JP (5); CA (3); IT (5); US (5); FR (8); GB (3)