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

NCT ID: NCT03056040

Last Updated: 2025-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 202 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-17
• Study Completion Date: 2022-02-21

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.

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 4 years.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Study Design

• Allocation Method: NA
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 4 years.

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: 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.

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 4 years.

Group Type: ACTIVE_COMPARATOR

Ravulizumab

Intervention Type: 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.

Eculizumab

Intervention Type: BIOLOGICAL

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

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.

Intervention Type: BIOLOGICAL

Eculizumab

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

Intervention Type: BIOLOGICAL

Other Intervention Names

ALXN1210; ULTOMIRIS

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Duarte, California, United States

Research Site

Los Angeles, California, United States

Research Site

Baltimore, Maryland, United States

Research Site

Detroit, Michigan, United States

Research Site

The Bronx, New York, United States

Research Site

Canberra, , Australia

Research Site

Kogarah, , Australia

Research Site

Liverpool, , Australia

Research Site

Melbourne, , Australia

Research Site

Woolloongabba, , Australia

Research Site

Toronto, Ontario, Canada

Research Site

Toronto, Ontario, Canada

Research Site

Montreal, Quebec, Canada

Research Site

Amiens, , France

Research Site

La Tronche, , France

Research Site

Marseille, , France

Research Site

Nice, , France

Research Site

Paris, , France

Research Site

Pierre-Bénite, , France

Research Site

Saint-Priest-en-Jarez, , France

Research Site

Strasbourg, , France

Research Site

Aachen, , Germany

Research Site

Essen, , Germany

Research Site

Ulm, , Germany

Research Site

Florence, , Italy

Research Site

Milan, , Italy

Research Site

Napoli, , Italy

Research Site

Torino, , Italy

Research Site

Vicenza, , Italy

Research Site

Fukushima, , Japan

Research Site

Kanazawa, , Japan

Research Site

Shinagawa-ku, , Japan

Research Site

Suita-shi, , Japan

Research Site

Suwa-shi, , Japan

Research Site

Maastricht, , Netherlands

Research Site

Nijmegen, , Netherlands

Research Site

Bucheon-si, , South Korea

Research Site

Daegu, , South Korea

Research Site

Daejeon, , South Korea

Research Site

Incheon, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Suwon, , South Korea

Research Site

Barcelona, , Spain

Research Site

Madrid, , Spain

Research Site

Majadahonda, , Spain

Research Site

Airdrie, , United Kingdom

Research Site

Leeds, , United Kingdom

Research Site

London, , United Kingdom

Countries

United States; Australia; Canada; France; Germany; Italy; Japan; Netherlands; South Korea; Spain; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 30510079 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31949012 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32869125 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35502600 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33301613 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32449174 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33178408 (View on PubMed)

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

Reference Type: 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.

Reference Type: DERIVED

PMID: 39841198 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34526067 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=ALXN1210-PNH-302&amp;attachmentIdentifier=c826be5c-044d-4dab-9e62-2d48684248c7&amp;fileName=ALXN1210-PNH-302-CSR_Synopsis_redacted.pdf&amp;versionIdentifier=

Related Info

Other Identifiers

2016-002026-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALXN1210-PNH-302

Identifier Type: -

Identifier Source: org_study_id