E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Warm Autoimmune Hemolytic Anemia |
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E.1.1.1 | Medical condition in easily understood language |
Warm Autoimmune Hemolytic Anemia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003825 |
E.1.2 | Term | Autoimmune hemolytic anemia |
E.1.2 | System Organ Class | 100000004851 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this repeat dose Phase 2 study are as follows: • To evaluate the safety and tolerability of two once-weekly intravenous infusions of 100 mg/kg ANX005 in patients with wAIHA • To evaluate the clinical effect of two once-weekly intravenous infusions of 100 mg/kg ANX005 in patients with wAIHA |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are as follows: • To evaluate the pharmacokinetic (PK) profile of ANX005 in subjects with wAIHA • To evaluate the effect of ANX005 on classical complement pathway inhibition as measured by complement system related biomarkers in subjects with wAIHA
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet ALL the following criteria to be eligible to participate in the study: 1. Male or female ≥18 years of age on the day of signing informed consent 2. Diagnosis of wAIHA at least 3 months prior to screening with a DAT ≥ 1 positive for IgG ±C3, or a diagnosis of mixed AIHA that is DAT positive for both IgG and C3, with a presence of a cold antibody with a thermal amplitude ≥30ºC 3. Hemoglobin level ≤10.0 g/dL (pre-transfusion) in wAIHA-01 within 6 weeks of the Day 1 dosing day or during the wAIHA-02 Week -6 or rescreening visits 4. Evidence of classical complement pathway activation in wAIHA-01 within 6 weeks of the Day 1 dosing date or during the wAIHA-02 screening period: a. Serum complement component 4 (C4) level no greater than 1.5 times the lower limit of normal and/or b. CH50 below the lower limit of normal (LLN) 5. Evidence of active hemolysis based on at least one of the following: a. LDH above the upper limit of normal (ULN) b. Indirect bilirubin above the ULN c. Haptoglobin below the LLN 6. Patients must have been previously vaccinated for encapsulated bacteria within 5 years prior to screening or be willing to receive prophylaxis against infections with encapsulated bacteria via vaccination and/or the use of prophylactic antibiotics in accordance with local standards of practice and/or guidelines. |
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E.4 | Principal exclusion criteria |
Subjects must not meet any of the following criteria: 1. Active lymphoma, lymphoproliferative disorder, or other malignancy requiring therapy and/or not clinically stable or in remission for at least 3 months prior to screening 2. Elevated aspartate aminotransferase or alanine aminotransferase levels > 2.5 times the upper limit of normal at screening unless associated with wAIHA 3. Platelet count < 30 x 10^9/L at screening 4. History of isolated cold agglutinin disease 5. History of solid organ, bone marrow, or stem cell transplantation 6. History of splenectomy within the 3 months prior to screening 7. Received rituximab or other B cell depleting monoclonal antibody (eg. daratumumab) <90 days prior to screening 8. Signs and symptoms of or a diagnosis consistent with a chronic autoimmune disorder and/or an ANA titer ≥1:160 9. Known genetic deficiencies of the complement cascade system |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Number and percent of patients experiencing treatment-emergent adverse events (TEAEs) • Change from baseline in hemoglobin over time up to Day 71 • Change from baseline in biomarkers of hemolysis (reticulocyte count, haptoglobin, LDH, total and indirect bilirubin) over time up to Day 71 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• ANX005 plasma concentration profiles and PK parameters such as AUC, Cmax, Tmax, accumulation ratio, t1/2, λz, CL and Vss • Inhibition of classical complement activity as measured by serum CH50 from baseline over time up to Day 71 • Change and percent change from baseline in serum C4 concentrations over time up to Day 71 • Change and percent change from baseline in serum free C1q concentrations over time up to Day 71 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
United States |
Austria |
France |
Bulgaria |
Spain |
Czechia |
Germany |
Italy |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |