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 is as follows:
• To evaluate the safety, tolerability, and proof of concept of two once-weekly intravenous infusions of 100 mg/kg ANX005 in subjects 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
• To assess the effect of 2 once-weekly doses of ANX005 on the following disease activity markers in subjects with wAIHA: Hemoglobin, Lactate dehydrogenase (LDH), Total and Indirect bilirubin, Haptoglobin, Reticulocyte count, Platelet count, CRP, Direct Antibody Test (DAT). |
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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 non-pregnant, non-lactating female ≥ 18 years of age on the day of signing informed consent
2. Diagnosis of wAIHA at least 3 months prior to screening
3. Hgb level > 10.0 g/dL (pre-transfusion) with no alternative explanation for anemia apart from wAIHA at screening
4. Positive direct antiglobulin test (DAT) ≥ 1 + for C3d and IgG
5. Evidence of classical complement pathway activation by one of the below:
a. Serum complement component 4 (C4) below the lower limit of normal
b. CH50 below the lower limit of normal
6. Evidence of active hemolysis based on at least one of the following:
a. LDH above the ULN
b. Indirect bilirubin above the ULN
c. Haptoglobin below the LLN
7. Vaccinations against encapsulated bacterial organisms (N. meningitidis, H. influenzae and S.
pneumoniae) within 5 years prior to screening or subject must be willing to complete vaccinations at least 2 weeks prior to dosing with ANX005. Documentation of vaccinations must be received at the study site in advance of the scheduled screening visit
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E.4 | Principal exclusion criteria |
Subjects must not meet any of the following criteria:
1. History of or current lymphoma or lymphoproliferative disorder requiring therapy
2. Elevated aspartate aminotransferase or alanine aminotransferase levels > 2.5 times the upper
limit of normal at screening
3. Platelet count < 30 x 109/L
4. History of cold agglutinin disease or IgM cold agglutinin titer > 1:64
5. History of solid organ, bone marrow, or stem cell transplantation
6. History of splenectomy within the 3 months prior to screening
7. Other wAIHA treatments:
- Received rituximab or other anti-CD20 monoclonal antibody < 3 months prior to screening
- Receiving steroids > 1 mg/kg of prednisone or equivalent daily at screening
8. Signs and symptoms of, or a diagnosis consistent with, a chronic autoimmune disorder not
resulting from primary wAIHA and/or an ANA titer of ≥ 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) |
Adverse events, infusion related reactions, safety laboratory assessments (serum chemistry, hematology, urine analysis), and vital signs. |
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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) |
Pharmacokinetic (PK) endpoints are:
-Maximum observed serum concentration (Cmax)
-Observed time to Cmax (Tmax)
-Area under the ANX005 serum concentration-time curve to the last sample (AUC0-t) and
extrapolated through infinity
-Accumulation ratio
-Terminal half-life (t1/2)
-Terminal elimination rate constant
-Clearance (CL)
-Volume of distribution (Vss)
Pharmacodynamics (PD) Endpoints:
-Hemoglobin
-Lactate dehydrogenase (LDH)
-Total and Indirect bilirubin
-Haptoglobin
-Reticulocyte count
-Platelet count
-Direct Antibody Test (DAT) |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Proof-of-Concept of Intravenous ANX005 in Subjects with Warm Autoimmune
Hemolytic Anemia |
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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
| 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 | 12 |
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 |
Austria |
France |
Germany |
Hungary |
Italy |
Netherlands |
Norway |
Spain |
United Kingdom |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |