ALXN1210 (Ravulizumab) Versus Eculizumab in Complement Inhibitor Treatment-Naïve Adult Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

NCT ID: NCT02946463

Last Updated: 2024-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 272 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-12
• Study Completion Date: 2023-02-28

Brief Summary

The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult participants with PNH who had never been treated with a complement inhibitor (treatment-naïve).

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 26-week Primary Evaluation Period, all participants had the opportunity to enter the Extension Period, wherein participants will receive ravulizumab for up to 5 years.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Study Design

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

Study Groups

Ravulizumab

Group Type: EXPERIMENTAL

Ravulizumab

Intervention Type: BIOLOGICAL

All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to \<60 kilogram (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

Group Type: ACTIVE_COMPARATOR

Ravulizumab

Intervention Type: BIOLOGICAL

All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to \<60 kilogram (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 were administered induction doses of 600 mg followed by maintenance doses of 900 mg.

Interventions

Ravulizumab

All treatments were given as intravenous (IV) infusions. For participants weighing ≥40 to \<60 kilogram (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 were administered induction doses of 600 mg followed by maintenance doses of 900 mg.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

Criteria For Patient Cohort Originally Enrolled in ALXN1210-PNH-301 Study: Inclusion Criteria: 1. Male or female ≥18 years of age. 2. PNH diagnosis confirmed by documented by high-sensitivity flow cytometry. 3. Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin <10 gram/deciliter), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of packed red blood cells (pRBC) transfusion due to PNH. 4. Lactate dehydrogenase (LDH) level ≥1.5 times the upper limit of normal at screening. 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

Exclusion Criteria: 1. Treatment with a complement inhibitor at any time. 2. History of bone marrow transplantation. 3. Body weight <40 kg. 4. Females who are pregnant, breastfeeding, or who have a positive pregnancy test at screening or Day 1. 5. Participation in another interventional clinical study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater. 6. History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease that, in the opinion of the investigator or sponsor, would preclude participation. 7. Unstable medical conditions (for example, myocardial ischemia, active gastrointestinal bleed, severe congestive heart failure, anticipated need for major surgery within 6 months of randomization, coexisting chronic anemia unrelated to PNH). Eligibility Criteria For Roll-over Cohort: 1. All participants regardless of age, who are currently receiving ALXN1210 IV in an ongoing ALXN1210 study in patients with PNH 2. Participants must be willing and able to give written informed consent and to comply with all Extension study visits and procedures, including the use of any data collection device(s) to directly record patient data 3. Females of childbearing potential and male patients with female partners of childbearing potential must use highly effective contraception continuing until at least 8 months after the last dose of ravulizumab.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Los Angeles, California, United States

Research Site

Whittier, California, United States

Research Site

Fort Worth, Texas, United States

Research Site

Buenos Aires, , Argentina

Research Site

Buenos Aires, , Argentina

Research Site

Córdoba, , Argentina

Research Site

Perth, , Australia

Research Site

Linz, , Austria

Research Site

Vienna, , Austria

Research Site

Brussels, , Belgium

Research Site

Hasselt, , Belgium

Research Site

Leuven, , Belgium

Research Site

Rio de Janeiro, , Brazil

Research Site

Salvador, , Brazil

Research Site

São Paulo, , Brazil

Research Site

São Paulo, , Brazil

Research Site

Edmonton, Alberta, Canada

Research Site

Toronto, Ontario, Canada

Research Site

Pilsen, , Czechia

Research Site

Prague, , Czechia

Research Site

Tallinn, , Estonia

Research Site

Limoges, , France

Research Site

Montpellier, , France

Research Site

Paris, , France

Research Site

Pierre-Bénite, , France

Research Site

Poitiers, , France

Research Site

Rennes, , France

Research Site

Aachen, , Germany

Research Site

Essen, , Germany

Research Site

Ulm, , Germany

Research Site

Ascoli Piceno, , Italy

Research Site

Florence, , Italy

Research Site

Milan, , Italy

Research Site

Napoli, , Italy

Research Site

Vicenza, , Italy

Research Site

Bunkyō City, , Japan

Research Site

Bunkyō City, , Japan

Research Site

Fukuoka, , Japan

Research Site

Fukushima, , Japan

Research Site

Hamamatsu, , Japan

Research Site

Kanazawa, , Japan

Research Site

Kitakyusyu-shi, , Japan

Research Site

Koshigaya-shi, , Japan

Research Site

Kumamoto, , Japan

Research Site

Nagoya, , Japan

Research Site

Nishinomiya-shi, , Japan

Research Site

Ogaki-shi, , Japan

Research Site

Okayama, , Japan

Research Site

Okayama, , Japan

Research Site

Osakasayama-shi, , Japan

Research Site

Sapporo, , Japan

Research Site

Shimotsuke-shi, , Japan

Research Site

Shinjuku-ku, , Japan

Research Site

Shinjuku-ku, , Japan

Research Site

Suita, , Japan

Research Site

Tokorozawa-shi, , Japan

Research Site

Tokyo, , Japan

Research Site

Toyoake-shi, , Japan

Research Site

Tsukuba, , Japan

Research Site

Wakayama, , Japan

Research Site

George, , Malaysia

Research Site

Johor Bahru, , Malaysia

Research Site

Kota Bharu, , Malaysia

Research Site

Kota Bharu, , Malaysia

Research Site

Kota Kinabalu, , Malaysia

Research Site

Kuching, , Malaysia

Research Site

Miri, , Malaysia

Research Site

Sibu, , Malaysia

Research Site

Monterrey, , Mexico

Research Site

Gdansk, , Poland

Research Site

Warsaw, , Poland

Research Site

Arkhangelsk, , Russia

Research Site

Barnaul, , Russia

Research Site

Irkutsk, , Russia

Research Site

Kirov, , Russia

Research Site

Moscow, , Russia

Research Site

Moscow, , Russia

Research Site

Murmansk, , Russia

Research Site

Novosibirsk, , Russia

Research Site

Omsk, , Russia

Research Site

Petrozavodsk, , Russia

Research Site

Rostov-on-Don, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Saratov, , Russia

Research Site

Ufa, , Russia

Research Site

Belgrade, , Serbia

Research Site

Singapore, , Singapore

Research Site

Daejeon, , South Korea

Research Site

Goyang-si, , South Korea

Research Site

Incheon, , South Korea

Research Site

Jeonju, , South Korea

Research Site

JinJoo, , South Korea

Research Site

Junggu, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Songpa-gu, , South Korea

Research Site

Suwon, , South Korea

Research Site

Ulsan, , South Korea

Research Site

Madrid, , Spain

Research Site

Majadahonda, , Spain

Research Site

Uppsala, , Sweden

Research Site

Changhua, , Taiwan

Research Site

Hualien City, , Taiwan

Research Site

Taichung, , Taiwan

Research Site

Tainan City, , Taiwan

Research Site

Taipei, , Taiwan

Research Site

Bangkok, , Thailand

Research Site

Bangkok, , Thailand

Research Site

Songkhla, , Thailand

Research Site

Eskişehir, , Turkey (Türkiye)

Research Site

Airdrie, , United Kingdom

Research Site

Leeds, , United Kingdom

Research Site

London, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Canada; Czechia; Estonia; France; Germany; Italy; Japan; Malaysia; Mexico; Poland; Russia; Serbia; Singapore; South Korea; Spain; Sweden; Taiwan; Thailand; Turkey (Türkiye); United Kingdom

References

Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Fureder W, Ptushkin V, Rottinghaus ST, Volles L, Shafner L, Aguzzi R, Pradhan R, Schrezenmeier H, Hill A. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019 Feb 7;133(6):530-539. doi: 10.1182/blood-2018-09-876136. Epub 2018 Dec 3.

Reference Type: BACKGROUND

PMID: 30510080 (View on PubMed)

Schrezenmeier H, Kulasekararaj A, Mitchell L, de Latour RP, Devos T, Okamoto S, Wells R, Popoff E, Cheung A, Wang A, Tomazos I, Patel Y, Lee JW. Predictors for improvement in patient-reported outcomes: post hoc analysis of a phase 3 randomized, open-label study of eculizumab and ravulizumab in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria. Ann Hematol. 2024 Jan;103(1):5-15. doi: 10.1007/s00277-023-05483-0. Epub 2023 Oct 7.

Reference Type: DERIVED

PMID: 37804344 (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)

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: DERIVED

PMID: 33178408 (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: DERIVED

PMID: 32869125 (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: DERIVED

PMID: 31949012 (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-301&amp;attachmentIdentifier=dadc661d-a7a3-4ea9-8bde-01f258a0442b&amp;fileName=ALXN1210-PNH-301-CSR_Synopsis_redacted.pdf&amp;versionIdentifier=

Related Info

Other Identifiers

2016-002025-11

Identifier Type: -

Identifier Source: secondary_id

ALXN1210-PNH-301

Identifier Type: -

Identifier Source: org_study_id