Warm Autoimmune Hemolytic Anemia MedDRA version: 20.0 Level: LLT Classification code 10003825 Term: Autoimmune hemolytic anemia System Organ Class: 100000004851
Conditions
Interventions
Product Name: RVT-1401
Product Code: RVT-1401
Pharmaceutical Form: Solution for injection
INN or Proposed INN: RVT-1401
Other descriptive name: RVT-1401
Concentration unit: mg/ml milligram(s)/millilit
Sponsors
Immunovant Sciences GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female = 18 years of age. 2. Diagnosis of primary or secondary WAIHA as documented by a positive direct antiglobulin test (DAT) specific for anti-IgG alone or anti-IgG plus C3d. 3. Secondary WAIHA may only include Stage 0 chronic lymphocytic leukemia (CLL) in which separate treatment is not indicated, nor anticipated to require active management for the duration of the study. 4. Have failed or not tolerated at least one prior WAIHA treatment regimen as per local standards (e.g., steroids, rituximab, azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil (MMF), danazol, or vincristine). Failure is defined as worsening or refractory disease despite steroids and or immunosuppressants 5. Participants with splenectomy =3 months from Day 1 who are up to date on vaccinations (based on age and local guidance) are allowed. 6. Haptoglobin upper limit of normal (ULN). 7. At Screening and Baseline, subject's hemoglobin level must be =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Participants with other types of AIHA (e.g., cold antibody AIHA, cold agglutinin syndrome, mixed type AIHA, or paroxysmal cold hemoglobinuria). 2. Participants requiring more than 2 units of RBC per week in the 2 weeks prior to Screening and Baseline. 3. Use of rituximab, any monoclonal antibody for immunomodulation, or proteasome inhibitor, within the past 3 months prior to Screening. 4. Immunoglobulins given by SC, IV (IVIG), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 60 days before Screening. 5. Total IgG level <6 g/L (at Screening). 6. Absolute neutrophil count <1000 cells/mm3(at Screening). 7. Albumin level <3.5 g/dL at Screening. 8. Known advanced liver disease including any diagnosis of cirrhosis of any stage. Non- alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) is allowable if there has been a recent (within 6 months) normal ultrasound, CT, or MRI. If the ultrasound, CT, or MRI demonstrate fatty changes alone, the participant may be enrolled if s/he has a normal range fibroscan for liver fibrosis. 9. AST or ALT =1.5x ULN at Screening. The participant may only be enrolled if s/he has a recent (within 6 months) normal ultrasound, CT, or MRI. If the ultrasound, CT, or MRI demonstrate fatty changes alone, the participant may be enrolled if s/he has a normal range fibroscan for liver fibrosis. 10. Participant has any laboratory abnormality (at screening) that, in the opinion of the investigator, is clinically significant, has not resolved at baseline, and could jeopardize or would compromise the participant's ability to participate in this study. 11. Medical history of primary immunodeficiency, T-cell or humoral, including common variable immunodeficiency. 12. Have an active infection, a recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to Screening. 13. History of or known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or Mycobacterium tuberculosis: - Participants must have negative test results for HBV surface antigen, HBV core antibody, HIV 1 and 2 antibodies, and a negative QuantiFERON-TB Gold test at Screening. - Participants with an indeterminate QuantiFERON-TB Gold test result will be allowed one retest; if not negative on retesting, the participant will be excluded. 14. Infection with hepatitis C virus (HCV): - Participants must have a negative test result for HCV antibody. or - Participants with a known history of HCV must have documented evidence of sustained virologic response that is consistent with cure of hepatitis C infection. This is defined as undetectable or unquantifiable HCV RNA at least 12 weeks after stopping HCV treatment (HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C; 2014-2018, AASLD and IDSA). This should be confirmed with a negative HCV RNA test at Screening. 15. Active malignancy or history of malignancy in the 3 years prior to screening (exclusive of non-melanoma skin cancer and cervical cancer in situ). 16. Participant has any medical condition (acute or chronic illness) or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the participant's ability to participate in this study. 17. Body Mass Index (BMI) at Screening = 40 kg/m2. 18. Use of investigational drug within 60 days or 5 half-lives of the drug (whichever is longer) before Screening. 19. Participant ha
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the effect of RVT-1401 on proportion of responders (defined as Hb level =10g/dL with at least a =2 g/dL increase from baseline without rescue therapy or blood transfusions in the previous two weeks). To assess the safety and tolerability of RVT-1401 in subjects with WAIHA;Secondary Objective: To examine the effect of RVT-1401 on change in Hb levels To examine the effect of RVT-1401 on time to response To examine the effect of RVT-1401 on change in hematocrit levels To examine the effect of RVT-1401 on proportion of participants with Hb levels in the normal range To examine the effect of RVT-1401 on time to achieving Hb levels in the normal range To examine the effect of RVT-1401 on change in fatigue To examine the effect of RVT-1401 on change in dyspnea To examine the effect of RVT-1401 on change in health-related quality of life To assess the change in serum levels of total IgG & IgG subclasses (I-IV) To examine RVT-1401 PK following repeated doses in patients with WAIHA To assess the changes in LDH, bilirubin,haptoglobin To measure anti-RVT-1401 antibodies following repeated doses in patients with WAIHA;Primary end point(s): Proportion of responders at week 13 Assessment of safety and tolerability by analysis of adverse event (AE) data and changes from baseline in vital signs, ECGs, and clinical laboratory values;Timepoint(s) of evaluation of this end point: week 13 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline in Hb levels Time to response Change from baseline in hematocrit levels Proportion of participants with Hb levels in the normal range at week 13 Time to achieving Hb levels in the normal range Change from baseline in FACIT-F score Change from baseline in Medical Research Council (MRC) breathlessness scale Change from baseline in EQ-5D-3L score Change from baseline in levels of total IgG & IgG subclasses (I-IV) Concentration of RVT-1401 pre-dose (Ctrough) Change from baseline in LDH, bilirubin, and haptoglobin Immunogenicity determined by change from pre-dose in anti-RVT-1401 antibodies, and characterization of any anti-RVT-1401 to confirm neutralization potential.;Timepoint(s) of evaluation of this end point: week 13 | — |
Countries
Israel, Korea, Republic of, Romania, Spain, Thailand, United Kingdom, United States
Contacts
Public ContactVP Regulatory Affairs
Immunovant Sciences GmbH
Outcome results
None listed