on-randomized, open-label study to investigate the efficacy, safety and tolerability of RVT-1401 for the Treatment of Patients with Warm Autoimmune Hemolytic Anemia
- Conditions
- Warm Autoimmune Hemolytic AnemiaMedDRA version: 20.0Level: LLTClassification code 10003825Term: Autoimmune hemolytic anemiaSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-003924-19-BG
- Lead Sponsor
- Immunovant Sciences GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 16
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 < lower limit of normal (LLN) and lactate dehydrogenase (LDH) >upper limit of normal (ULN).
7. At Screening and Baseline, subject's hemoglobin level must be <10 g/dL and the subject must have documented symptoms related to anemia (e.g., weakness, dizziness, fatigue, shortness of breath, chest pain).
8. Karnofsky Performance status = 60.
9. Subject's concurrent treatment for WAIHA may consist only of steroids (stable dose for at least two weeks prior to Day 1), immunosuppressant therapy (azathioprine, MMF, or cyclosporine) that has been at a stable dose for at least four weeks prior to Day 1, or erythropoietin (stable dose for at least 6 weeks prior to Day 1). [Note: starting doses of WAIHA therapy must be maintained throughout the study except in the case of a rescue medication as per local standards for safety. Steroid taper down to 10 mg/day will be allowed for participants who achieve response for at least 2 weeks.]
10. A female participant is eligible to participate if she is of:
a. Non-childbearing potential defined as pre-menopausal females with a documented bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy; hysteroscopic sterilization, or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) in the post-menopausal range is confirmatory].
b. Child-bearing potential and agrees to use one of the contraception methods listed in Section 6.6.1 for an appropriate period of time (as determined by the product label or Principal Investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female participants must agree to use contraception until 90 days after the last dose of study treatment.
11. Male participants must agree to use one of the contraception methods listed in Section 6.6.1. This criterion must be followed from the time of the first dose of study treatment until 90 days after the last dose of study treatment.
12. Willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method