A Phase 2, Multicenter, Non-Randomized, Open-Label Study of RVT-1401 for the Treatment of Patients With Warm Autoimmune Hemolytic Anemia
Overview
- Phase
- Phase 2
- Intervention
- RVT-1401 680 mg/weekly
- Conditions
- Warm Autoimmune Hemolytic Anemia
- Sponsor
- Immunovant Sciences GmbH
- Enrollment
- 5
- Locations
- 21
- Primary Endpoint
- Number of Responders at Week 13
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief 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.
Detailed Description
This is a Phase 2, non-randomized, sequential, open-label study to investigate the safety, tolerability, PK, PD, and efficacy of RVT-1401 (680 mg/weekly and 340 mg/weekly) in patients with Warm Autoimmune Hemolytic Anemia that is worsening or refractory in spite of therapy with steroids and or immunosuppressants or worsening with steroid or immunosuppressant taper. Two cohorts of participants will be enrolled in a non-randomized sequential approach. Participants will be enrolled into Cohort 1 (680 mg/weekly) first followed by Cohort 2 (340 mg/weekly). Following the initial dose at the Baseline Visit (Week 1, Day 1), study visits will occur weekly throughout the treatment period. Following the final dose at Week 12, visits will occur weekly through Week 14 and then at Week 16 and Week 20. Safety, PK, PD, and clinical assessments will be collected throughout the study. Each participant will participate in the study for up to approximately 24 weeks: up to a 4-week screening period, a 12-week treatment period, and an 8-week follow up period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female ≥ 18 years of age.
- •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.
- •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.
- •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.
- •Participants with splenectomy ≥3 months from Day 1 who are up to date on vaccinations (based on age and local guidance) are allowed.
- •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).
- •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). \[Note: starting doses of WAIHA therapy must be maintained throughout the study except in the case of a rescue medication as per local standards for safety. Steroid taper down to 10 mg/day will be allowed for participants who achieve response for at least 2 weeks.\]
- •A female participant is eligible to participate if she is of:
- •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.
- •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.
Exclusion Criteria
- •Participants with other types of AIHA (e.g., cold antibody AIHA, cold agglutinin syndrome, mixed type AIHA, or paroxysmal cold hemoglobinuria).
- •Participants requiring more than 2 units of RBC per week in the 2 weeks prior to Screening and Baseline.
- •Use of rituximab, any monoclonal antibody for immunomodulation, or proteasome inhibitor, within the past 3 months prior to Screening.
- •Immunoglobulins given by SC, IV (IVIG), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 60 days before Screening.
- •Total IgG level \<6 g/L (at Screening).
- •Absolute neutrophil count \<1000 cells/mm3(at Screening).
- •Other, more specific exclusion criteria are defined in the protocol.
Arms & Interventions
Cohort 1
Dosing Regimen A - 680 mg weekly for 12 weeks via once weekly subcutaneous (SC) injections
Intervention: RVT-1401 680 mg/weekly
Cohort 2
Dosing Regimen B - 340 mg weekly for 12 weeks via once weekly subcutaneous (SC) injections
Intervention: RVT-1401 340 mg/weekly
Outcomes
Primary Outcomes
Number of Responders at Week 13
Time Frame: Week 13
Responders were defined as the participants with level of hemoglobin (Hb) \>=10 grams per deciliter (g/dL) with at least a \>=2 g/dL increase from Baseline without rescue therapy or blood transfusions in the previous two weeks.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Serious AE (SAE), Treatment-related Adverse Event (AE), and Death
Time Frame: Up to Week 20
AEs were defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Clinically significant changes determined by the Investigator such as vital signs, Electrocardiograms (ECGs), and clinical laboratory values were also reported as AEs. TEAEs were defined as AEs that either started on or after the date of the first dose of study drug. SAEs were defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention to prevent one of the other outcomes listed in the definition.
Secondary Outcomes
- Time to Response(Up to Week 13)
- Time to Achieving Hb Levels in the Normal Range(Up to Week 13)
- Number of Participants With Change in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Score(Up to Week 13)
- Number of Participants With Change in Medical Research Council (MRC) Breathlessness Scale(Up to Week 13)
- Number of Participants With Change in Euro Quality-5 Dimension-3 Level (EQ-5D-3L) Score(Up to Week 20)
- Concentration of RVT-1401 Pre-dose(Pre-dose, Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 13 post-dose)
- Number of Participants With Presence of Anti-RVT 1401 Antibodies(Pre-dose on Weeks 1, 3, 5, 8, 13 and Week 20)
- Number of Participants With Change in Levels of Total Immunoglobulin (Ig)G and IgG Subclasses (1-4)(Up to Week 20)