E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Warm Autoimmune Hemolytic Anemia |
|
E.1.1.1 | Medical condition in easily understood language |
Warm Autoimmune Hemolytic Anemia |
|
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 |
|
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 |
|
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 |
|
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 (see Section 7.1.6 for details) 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 c. Complement component deposition on the cell surface assessed by flow cytometry 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 7. 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.
|
|
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 109/L 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
|
|
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 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
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 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |