Study to Assess the Safety and Tolerability of Tafasitamab in Adult Participants With Primary Autoimmune Blood Cell Disorders

Официальное название

A Phase 2a, Open-Label, Multicenter Study of Tafasitamab in Adult Participants With Primary Autoimmune Blood Cell Disorders

Обзор

This study will evaluate the safety and efficacy of tafasitamab in adult participants with primary autoimmune blood cell disorders.

Вмешательства

• Препарат INCA000585
  Tafasitamab will be administered intravenously at protocol defined timepoints.

Первичные конечные точки

• Number of participants with Treatment-emergent Adverse Events (TEAEs) [Срок оценки: Up to 52 weeks]
• Stable platelet response [Срок оценки: After Day 56 up to Week 48]
• Stable hemoglobin response [Срок оценки: After Day 56 up to Week 48]

Вторичные конечные точки (12)

• Complete Response (CR) [Срок оценки: Week 24]
• CR (complete remission) [Срок оценки: Week 48]
• Partial Response (PR) [Срок оценки: Week 24]
• Duration of stable platelet response [Срок оценки: Up to Week 48]
• Duration of CR [Срок оценки: Up to Week 48]
• Duration of response [Срок оценки: Up to Week 48]
• CR [Срок оценки: Week 24]
• CR (Complete remission) [Срок оценки: Week 48]
• PR [Срок оценки: Week 24]
• Duration of stable hemoglobin response [Срок оценки: Up to Week 48]
• Duration of CR [Срок оценки: Up to Week 48]
• Duration of response [Срок оценки: Up to Week 48]

Критерии участия

Критерии включения

\- Ability to comprehend and willingness to sign a written ICF for the study.

• Aged ≥ 18 years.
• Confirmed historical diagnosis of one of the following autoimmune blood disorders:

• Primary ITP.
• Primary wAIHA.
• No history of splenectomy.
• Confirmed transient response to at least 1 prior early-line treatment (eg, corticosteroids, IVIG, rituximab):

• Primary ITP: Increase in platelet count to ≥ 30 × 109/L with at least a 2-fold increase of baseline platelet count.
• Primary wAIHA: Increase in hemoglobin to ≥ 10 g/dL with an increase of at least 2 g/dL from baseline.
• Received ≥ 1 standard course of rituximab (375 mg/kg × 4 weekly doses or 2 doses of 1000 mg flat dose every 2 weeks) with last dose given at least 6 months prior to initiation of study treatment. Note: If rituximab was the only prior therapy, individuals with NR to rituximab will not be eligible.

• Primary ITP: a PR (platelet count ≥ 30 × 109/L with at least a 2-fold increase of baseline platelet count) within 6 months of the last administered dose followed by relapse OR a CR (platelet count > 100 × 109/L) lasting < 48 weeks OR NR (platelet count < 30 × 109/L or less than 2-fold increase of baseline platelet count or bleeding) within 6 months of the last administered dose.
• Primary wAIHA: a PR with hemoglobin ≥ 10 g/dL and with an increase of at least 2 g/dL from baseline OR a CR (hemoglobin ≥ 12 g/dL and normalization of hemolytic markers) OR NR (hemoglobin < 10 g/dL or < 2 g/dL increase of baseline hemoglobin).
• Persistent or chronic active primary ITP or active primary wAIHA with indication for treatment at the time of inclusion.

• Primary ITP: platelet count < 30 × 109/L within the 15 days before treatment is scheduled to begin (Day 1).

Note: Participants treated with a rescue therapy during screening in response to a documented platelet count < 30 × 109/L are eligible, irrespective of platelet count within 15 days of Day 1.

• Primary wAIHA: hemoglobin < 10 g/dL documented with DAT result positive for IgG, with or without C3d, and evidence of hemolysis based on low haptoglobin, elevated LDH, and/or indirect bilirubin.

• ECOG performance status of 0 to 2.
• Willingness to avoid pregnancy or fathering children.
• Further inclusion criteria apply.

Критерии исключения

• Clinical manifestations typical for cold agglutinin disease.
• Life-threatening bleeding or urgent need to elevate the platelet count for primary ITP or hemodynamic instability or hemoglobin < 6 g/dL with urgent need to elevate hemoglobin for primary wAIHA within 2 weeks prior to Day 1.
• Prior treatment with anti-CD19 therapy (eg, mAb, bispecific T-cell engager, or CAR T cell) for any indication.
• Previous severe allergic reaction to a mAb or known allergy to any component/excipient of tafasitamab.
• Changes in doses (> 10%) of permitted disease-related therapies, including oral corticosteroids and TPO-RA (primary ITP participants) within 2 weeks prior to Day 1, or change in ESA (primary wAIHA participants) dose within 2 weeks prior to Day 1.
• Evidence of hypogammaglobulinemia during screening (IgA < 70 mg/dL, IgG < 700 mg/dL, and/or IgM < 40 mg/dL) and frequent and/or severe infections.
• Women who are pregnant or breastfeeding.
• History of malignancy except for the following:

• Malignancy treated with curative intent with no evidence of active disease for more than 2 years before screening.
• Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanoma skin cancer.
• Adequately treated carcinoma in situ without current evidence of disease.
• Congestive heart failure (left ventricular ejection fraction of < 50%, assessed by 2 dimensional echocardiography or a multigated acquisition scan).
• Participants with:

• Known positive test result for HCV (with HCV antibody serology testing) and a positive test for HCV RNA.

Note: Participants with positive serology must have been tested for HCV RNA and are eligible only in the case of negative HCV RNA test result.

• Known positive test result for chronic HBV infection (defined by HBsAg positivity or positive HBV DNA test result).

Note: Participants with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA was undetectable, provided that they are willing to undergo monthly ongoing DNA testing. Antiviral prophylaxis may be administered as per institutional guidelines.

Note: Participants who have protective titers of HBsAb (HBsAb positive, HBcAb negative, and HBsAg negative) after vaccination or prior HBV infection are eligible.

• Seropositivity for or history of active viral infection with HIV.

• Active systemic infection (including infection with SARS-CoV-2).
• Participants in a severely immunocompromised state, per investigator's clinical assessment.
• Receipt of a live-attenuated vaccine within 4 weeks prior to the first infusion of tafasitamab (inactivated and killed vaccines are acceptable).
• Coagulation or platelet function abnormality.
• An active medical condition with a strong indication for treatment with anticoagulation agents (eg, intracoronary stent within 12 months).
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
• Toxicities related to prior therapies must be CTCAE (v5.0) ≤ Grade 1 at the time of study treatment/enrollment (except for chronic toxicities \[≤ Grade 2\] not expected to resolve).
• Chronic infectious disease requiring systemic antibiotics or antifungal or antiviral medications.
• Unwillingness to undergo transfusion with blood components.
• Current use of prohibited medication as described in the protocol.
• Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
• Further exclusion criteria apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 10 центров

• Palo Verde Cancer Specialists Palo Verde Hematology Oncology, Ltd Glendale — Glendale
• Usc Norris Comprehensive Cancer Center — Los Angeles
• Rocky Mountain Cancer Centers — Lone Tree
• Yale University School of Medicine — New Haven
• Gnp Research — Cooper City
• Beth Israel Deaconess Medical Center — Boston
• Montefiore Medical Center — The Bronx
• Inova Schar Cancer Institute — Fairfax
• … и ещё 2 центра

Италия · 8 центров

• Azienda Ospedaliero-Universitaria Orsola-Malpighi - Universita Degli Studi Di Bologna — Bologna
• Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia (Presidio Montichiari — Brescia
• Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori — Meldola
• Fondazione Irccs Ca' Granda - Ospedale Maggiore Policlinico — Milan
• Ospedale San Raffaele — Milan
• Azienda Ospedaliera Universitaria Federico Ii — Naples
• Azienda Ospedale Universita Di Padova — Padova
• Fondazione Policlinico Universitario Agostino Gemelli Irccs — Roma

Франция · 7 центров

• Chu Angers - Hôpital Hôtel Dieu — Angers
• Chu Caen - Hôpital de La Côte de Nacre — Caen
• Hôpital Henri Mondor — Créteil
• Chu Dijon - Hopital Du Bocage — Dijon
• Chu Bordeaux - Hôpital Haut-Lévêque — Pessac
• Hopital Purpan — Toulouse
• Chru de Nancy- Hopital de Brabois — Vandœuvre-lès-Nancy

Австралия · 6 центров

• St Vincent'S Hospital Sydney — Darlinghurst
• Townsville University Hospital — Douglas
• Princess Alexandra Hospital Australia — Woolloongabba
• Box Hill Hospital — Box Hill
• Monash Medical Centre Clayton — Clayton
• The Alfred Hospital — Melbourne

Нидерланды · 4 центра

• Amsterdam Umc, Locatie Vumc — Amsterdam
• Radboudumc — Nijmegen
• Erasmus Medisch Centrum — Rotterdam
• University Medical Center Utrecht — Utrecht

Великобритания · 3 центра

• Castle Hill Hospital — Cottingham
• Barts Hospital — London
• Plymouth Hospitals Nhs Trust — Plymouth

Испания · 2 центра

• Ico Badalona. Hospital Universitario Germans Trias I Pujol — Badalona
• Hospital Universitario La Paz — Madrid

Идентификаторы

NCT: NCT07104565 · INCA000585-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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