Clinical trial NCT04253236: To Assess the Efficacy and Safety of RVT-1401 in the Treatment of Warm Autoimmune Hemolytic Anemia (ASCEND-WAIHA).
Official title: A Phase 2, Multicenter, Non-Randomized, Open-Label Study of RVT-1401 for the Treatment of Patients With Warm Autoimmune Hemolytic Anemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Warm Autoimmune Hemolytic Anemia
Lead sponsor: Immunovant Sciences GmbH
Sponsor class: INDUSTRY
First posted: 2020-02-05
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Responders at Week 13
timeFrame: Week 13
measure: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Serious AE (SAE), Treatment-related Adverse Event (AE), and Death
timeFrame: Up to Week 20
Secondary outcomes:
measure: Time to Response
timeFrame: Up to Week 13
measure: Time to Achieving Hb Levels in the Normal Range
timeFrame: Up to Week 13
measure: Number of Participants With Change in Functional Assessment of Chronic Illness Therapy-fatigue (FACIT-F) Score
timeFrame: Up to Week 13
measure: Number of Participants With Change in Medical Research Council (MRC) Breathlessness Scale
timeFrame: Up to Week 13
measure: Number of Participants With Change in Euro Quality-5 Dimension-3 Level (EQ-5D-3L) Score
timeFrame: Up to Week 20
measure: Concentration of RVT-1401 Pre-dose
timeFrame: Pre-dose, Weeks 1, 2, 3, 4, 5, 6, 8, 10, 12 and 13 post-dose
measure: Number of Participants With Presence of Anti-RVT 1401 Antibodies
timeFrame: Pre-dose on Weeks 1, 3, 5, 8, 13 and Week 20
measure: Number of Participants With Change in Levels of Total Immunoglobulin (Ig)G and IgG Subclasses (1-4)
timeFrame: Up to Week 20
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center - Hematology/Oncology
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan - Internal Medicine Division of Hematology/Oncology
state: Michigan
city: Greenville
country: United States
facility: Leo W. Jenkins Cancer Center
state: North Carolina
city: Afula
country: Israel
facility: Ha'Emek Medical Center
city: Haifa
country: Israel
facility: Carmal MC
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital - Department of Internal Medicine
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitario Quirónsalud Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Quirón
city: Bangkok
country: Thailand
facility: Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital
city: Chiang Mai
country: Thailand
facility: Faculty of Medicine, Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital
city: Hat Yai
country: Thailand
facility: Faculty of Medicine, Prince of Songkla University,Songklanagarind Hospital
city: Khon Kaen
country: Thailand
facility: Faculty of Medicine, Khon Kaen University, Srinagarind Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
References: