To Assess the Efficacy and Safety of RVT-1401 in the Treatment of Warm Autoimmune Hemolytic Anemia (ASCEND-WAIHA).
Condition: Warm Autoimmune Hemolytic Anemia
MeSH terms: Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Hemolysis
Intervention: RVT-1401 680 mg/weekly; RVT-1401 340 mg/weekly
Intervention description: Non-randomized subjects will receive subcutaneous injection of 680 mg weekly for 12 weeks of RVT-1401; Non-randomized subjects will receive subcutaneous injection of 340 mg weekly for 12 weeks of RVT-1401
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a Phase 2 non-randomized, open-label study to investigate the efficacy, safety and
      tolerability of RVT-1401 in patients with Warm Autoimmune Hemolytic Anemia.
    

Eligibility 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. 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).

          7. 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.]

          8. A female participant is eligible to participate if she is of:

               1. 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.

               2. Child-bearing potential and agrees to use one of the contraception methods listed
                  in the protocol 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.

          9. Male participants must agree to use one of the contraception methods listed in the
             protocol. 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.

         10. Willing and capable of giving written informed consent, which includes compliance with
             the requirements and restrictions listed in the consent form.

        Other, more specific inclusion criteria are defined in the protocol.

        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).

        Other, more specific exclusion criteria are defined in the protocol.