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

NCT02946463 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: ALXN1210-PNH-3012016-002025-11
• Study Type: interventional
• Target: 272
• Locations: 23 countries
• Sites: 117

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).

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Outcome Measures

Primary Outcomes (2)

• Proportion Of Participants With Normalization Of Lactate Dehydrogenase (LDH) Levels

  LDH is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria (PNH). A decrease in LDH from above the upper limit of normal (ULN) to below the ULN indicates reduction (improvement) in hemolysis. Normalization of LDH levels (LDH-N) was LDH levels less than or equal to 1 x ULN, from Day 29 through Day 183. The ULN for LDH is 246 U/L.

  Day 29 through Day 183

• Percentage Of Participants Who Achieved Transfusion Avoidance (TA)

  Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines through Day 183.

  Baseline through Day 183

Secondary Outcomes (4)

• Percentage Of Participants With Breakthrough Hemolysis (BTH)

  Baseline through Day 183

• Percent Change From Baseline In LDH Levels

  Baseline, Day 183

• Change From Baseline In Quality Of Life As Assessed By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue

  Baseline, Day 183

• Percentage Of Participants With Stabilized Hemoglobin Levels

  Baseline through Day 183

Study Arms (2)

Ravulizumab

EXPERIMENTAL

Biological: Ravulizumab

Eculizumab

ACTIVE COMPARATOR

Biological: Ravulizumab; Biological: Eculizumab

Interventions

Ravulizumab 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; Ravulizumab

Eculizumab BIOLOGICAL

All treatments were given as IV infusions. Participants were administered induction doses of 600 mg followed by maintenance doses of 900 mg.

Eculizumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (120)

Research Site

Los Angeles, California, 90033, United States

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Whittier, California, 90603, United States

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Fort Worth, Texas, 76104, United States

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Buenos Aires, C1015ABO, Argentina

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Buenos Aires, C1425AUM, Argentina

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Córdoba, X5004BAL, Argentina

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Perth, 6000, Australia

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Linz, 4020, Austria

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Vienna, A-1090, Austria

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Brussels, 1200, Belgium

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Hasselt, 3500, Belgium

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Leuven, 3000, Belgium

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Rio de Janeiro, Brazil

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Salvador, 41253-190, Brazil

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São Paulo, 05403-000, Brazil

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São Paulo, Brazil

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Edmonton, Alberta, T6G 2G3, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Pilsen, 323 00, Czechia

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Prague, Czechia

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Tallinn, 13419, Estonia

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Limoges, 87042, France

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Montpellier, 34295, France

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Paris, 75475, France

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Pierre-Bénite, 69310, France

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Poitiers, 86021, France

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Rennes, 35033, France

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Aachen, 52074, Germany

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Essen, 45122, Germany

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Ulm, 89081, Germany

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Ascoli Piceno, 63100, Italy

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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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Vicenza, 36100, Italy

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Bunkyō City, 113-8431, Japan

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Bunkyō City, 113-8519, Japan

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Fukuoka, 812-8582, Japan

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Fukushima, 960-1295, Japan

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Hamamatsu, 432-8580, Japan

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Kanazawa, 920-8641, Japan

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Kitakyusyu-shi, 806-8501, Japan

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Koshigaya-shi, 343-8555, Japan

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Kumamoto, 860-8556, Japan

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Nagoya, 453-8511, Japan

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Nishinomiya-shi, 663-8501, Japan

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Ogaki-shi, 503-8502, Japan

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Okayama, 700-8558, Japan

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Okayama, 701-1192, Japan

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Osakasayama-shi, 589-8511, Japan

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Sapporo, 060-8543, Japan

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Shimotsuke-shi, 329-0498, Japan

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Shinjuku-ku, 160-0023, Japan

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Shinjuku-ku, 160-8582, Japan

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Suita, 565-0871, Japan

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Tokorozawa-shi, Japan

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Tokyo, Japan

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Toyoake-shi, 470-1192, Japan

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Tsukuba, 305-8576, Japan

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Wakayama, 641-8510, Japan

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George, 10990, Malaysia

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Johor Bahru, 80100, Malaysia

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Kota Bharu, 15586, Malaysia

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Kota Bharu, 16150, Malaysia

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Kota Kinabalu, 88586, Malaysia

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Kuching, 93586, Malaysia

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Miri, 98000, Malaysia

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Sibu, 96000, Malaysia

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Monterrey, 64460, Mexico

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Gdansk, 80-214, Poland

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Warsaw, 02-172, Poland

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Arkhangelsk, 163045, Russia

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Barnaul, 656024, Russia

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Irkutsk, 664079, Russia

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Kirov, 610027, Russia

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Moscow, 117997, Russia

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Moscow, 125284, Russia

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Murmansk, 183047, Russia

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Novosibirsk, 630091, Russia

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Omsk, 644013, Russia

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Petrozavodsk, 185019, Russia

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Rostov-on-Don, 344022, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, Russia

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Saratov, 410028, Russia

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Ufa, 450005, Russia

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Belgrade, 11000, Serbia

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Singapore, 119228, Singapore

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Daejeon, 35015, South Korea

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Goyang-si, 10408, South Korea

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Incheon, 21565, South Korea

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Jeonju, 561-712, South Korea

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JinJoo, 52727, South Korea

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Junggu, 41944, South Korea

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Seoul, 02841, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 04401, South Korea

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Seoul, 06591, South Korea

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Seoul, 07985, South Korea

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Seoul, 135-710, South Korea

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Seoul, 152703, South Korea

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Songpa-gu, 05505, South Korea

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Suwon, 16247, South Korea

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Ulsan, 44033, South Korea

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Madrid, 28040, Spain

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Majadahonda, 28220, Spain

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Uppsala, 75185, Sweden

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Changhua, 50006, Taiwan

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Hualien City, 97002, Taiwan

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Taichung, 404, Taiwan

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Tainan, 70403, Taiwan

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Taipei, 100, Taiwan

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Bangkok, 10330, Thailand

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Bangkok, 10700, Thailand

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Songkhla, 90110, Thailand

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Eskişehir, 26040, Turkey (Türkiye)

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Airdrie, ML6 0JS, United Kingdom

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Leeds, United Kingdom

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London, SE5 9NU, United Kingdom

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Related Publications (6)

• 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.

  PMID: 30510080 BACKGROUND

• 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.

  PMID: 37804344 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

• 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 DERIVED

• 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 DERIVED

• 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 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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: October 27, 2016
• Study Start: December 12, 2016
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: May 14, 2024
• Results First Posted: February 12, 2019

Record last verified: 2024-04

Locations

TH (3); TW (5); AR (3); CZ (2); FR (6); JP (25); SE (1); SG (1); DE (3); TU (1); KR (17); AU (2); GB (3); CA (2); PL (2); IT (5); BR (4); RU (15); MY (8); US (3); ME (1); BE (3); ES (2)