Study of the Efficacy and Safety of Parsaclisib in Participants With Primary Warm Autoimmune Hemolytic Anemia

Phase 3TerminatedNCT05073458

Incyte Corporation13 enrolled

Overview

The purpose of this study is to evaluate the efficacy and safety of parsaclisib compared with placebo in participants with Primary Warm Autoimmune Hemolytic Anemia (wAIHA),

Prospective participants must have primary wAIHA as well as other protocol-defined criteria. After participants have been determined to be eligible for the study, they will be randomized to 2:1, with stratification factor of corticosteroid dose and hemoglobin (Hgb \<9 g/dL or ≥ 9 g/dL). Once a participant has completed the week 24 assessments in the double-blind period, the participant will have the opportunity to receive parsaclisib in the open-label treatment which will last up to another 24 weeks. Participants may then continue to receive parsaclisib in a long-term extension period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Warm Autoimmune Hemolytic Anemia (wAIHA)

Interventions

parsaclisinibDRUG

parsaclisib will be administered QD orally

placeboDRUG

placebo will be administered QD orally follwed by Parsaclisinib in the open label period

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of primary warm AIHA. * Participants who have at least 1 unsuccessful prior therapy for warm AIHA or unable to receive or tolerate other therapies. * Hemoglobin ≥ 6.5 to \< 10 g/dL with symptoms of anemia at screening. * FACIT-F score ≤ 43 at screening. * Willingness to avoid pregnancy or fathering children. * Willingness to receive PJP prophylaxis. * Further inclusion criteria apply. Exclusion Criteria: * Women who are pregnant, breastfeeding or who are planning a pregnancy. * Diagnosis of other types of AIHA (CAD, cold agglutinin syndrome, mixed-type AIHA or paroxysmal cold hemoglobinuria). * Secondary warm AIHA from any cause or diagnosis of Evans syndrome. * Splenectomy less than 3 months before randomization. * Participants with a history or ongoing significant illness as assessed by the investigator. * Participants with a current of medical history of a malignancy within the past 5 years except basal or squamous cell skin cancer that has been removed and considered cured, or superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy. * Participants know to be infected with HIV, Hepatitis B, or hepatitis C. * Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine. * Participants with laboratory values outside of the protocol defined ranges. * Further exclusion criteria apply.

Locations (56)

Outcomes

Primary Outcomes

Percentage of Participants Attaining a Durable Hemoglobin Response

A durable hemoglobin response was defined as hemoglobin ≥10 grams per deciliter (g/dL) with an increase from Baseline of ≥2 g/dL not attributed to rescue therapy at ≥3 of the 4 available visits at Week 12 and/or later during the 24-week double-blind treatment period.

Time frame: up to Week 24

Secondary Outcomes

Percentage of Participants With a ≥3-point Increase From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Week 24

Time frame: Baseline; Week 24

Percentage of Participants With a 50 Meter Increase From Baseline to Week 24 in a 6-minute Walk Test (6MWT)

The 6MWT is used to evaluate submaximal exercise capacity. It is a self-paced measurement of the distance that a participant can quickly walk on a flat, hard surface in a period of 6 minutes.

Time frame: Baseline; Week 24

Change From Baseline in the FACIT-F Score at Each Post-Baseline Visit

The FACIT-F scale was developed to assess anemia-related fatigue. The FACIT-F is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function over the past 7 days. A clinically meaningful change in the FACIT-F score was defined as ≥3-point increase from Baseline. Item scores range from 0 ("not at all") to 4 ("very much"), and the total score ranges from 0 to 52; lower scores indicate greater fatigue. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. End of Treatment, Double-blind Period: assessment performed for participants who discontinued treatment before Week 24. End of Treatment, Open-label Period: assessment performed for participants who discontinued treatment after Week 24 and before Week 56. Follow-up Visit 3 occurred 12 weeks after the end of treatment visit.

Data from ClinicalTrials.gov

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Investigative Site US005

Los Angeles, California, United States

Investigative Site US004

Whittier, California, United States

Investigative Site US006

Miami, Florida, United States

Investigative Site US012

Indianapolis, Indiana, United States

Investigative Site US007

The Bronx, New York, United States

Investigative Site US002

The Bronx, New York, United States

Investigative Site US003

Greenville, North Carolina, United States

Investigative Site US009

Canton, Ohio, United States

Investigative Site US010

Easton, Pennsylvania, United States

Investigative Site US001

Knoxville, Tennessee, United States

...and 46 more locations

Time frame: Baseline; Day 1; Weeks 8, 12, 16, 20, 24, 28, 32, 40, 48, 56, and every 16 weeks post-Week 56

Percentage Change From Baseline in the FACIT-F Score at Each Post-Baseline Visit

The FACIT-F scale was developed to assess anemia-related fatigue. The FACIT-F is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function over the past 7 days. A clinically meaningful change in the FACIT-F score was defined as ≥3-point increase from Baseline. Item scores range from 0 ("not at all") to 4 ("very much"), and the total score ranges from 0 to 52; lower scores indicate greater fatigue. Percentage change from Baseline was calculated as (\[the post-Baseline value minus the Baseline value\]/Baseline value) x 100. End of Treatment, Double-blind Period: assessment performed for participants who discontinued treatment before Week 24. End of Treatment, Open-label Period: assessment performed for participants who discontinued treatment after Week 24 and before Week 56. Follow-up Visit 3 occurred 12 weeks after the end of treatment visit.

Time frame: Baseline; Day 1; Weeks 8, 12, 16, 20, 24, 28, 32, 40, 48, 56, and every 16 weeks post-Week 56

Change From Baseline in Hemoglobin at Each Post-Baseline Visit

Change from Baseline was calculated as the post-Baseline value minus the Baseline value. End of Treatment, Double-blind Period: assessment performed for participants who discontinued treatment before Week 24. End of Treatment, Open-label Period: assessment performed for participants who discontinued treatment after Week 24 and before Week 56. Follow-up Visits 1, 2, and 3 occurred 4, 8, and 12 weeks, respectively, after the end of treatment visit.

Time frame: Baseline; Day 1; Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, and every 8 weeks post-Week 56

Percentage Change From Baseline in Hemoglobin at Each Post-Baseline Visit

Percentage change from Baseline was calculated as (\[the post-Baseline value minus the Baseline value\]/Baseline value) x 100. End of Treatment, Double-blind Period: assessment performed for participants who discontinued treatment before Week 24. End of Treatment, Open-label Period: assessment performed for participants who discontinued treatment after Week 24 and before Week 56. Follow-up Visits 1, 2, and 3 occurred 4, 8, and 12 weeks, respectively, after the end of treatment visit.

Time frame: Baseline; Day 1; Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, and every 8 weeks post-Week 56

Percentage of Participants Who Received Transfusions From Week 6 to Week 24 and From Week 24 to Week 48

Transfusion was permitted as a rescue treatment. Rescue medication was to be considered if the absolute hemoglobin level continued to decline, there was a \> 1 g/dL decrease in hemoglobin from the prior assessment, or the participant developed new or worsening symptoms of warm autoimmune hemolytic anemia (wAIHA).

Time frame: Week 6 to Week 24; Week 24 to Week 48

Change From Baseline in Daily Corticosteroid Dose at Week 24

A new or increased dose of corticosteroids (prednisone or equivalent) from the Day 1 dose was permitted as rescue treatment. Rescue medication was to be considered if the absolute hemoglobin level continued to decline, there was a \> 1 g/dL decrease in hemoglobin from the prior assessment, or the participant developed new or worsening symptoms of wAIHA. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline; Week 24

Percentage Change From Baseline in Daily Corticosteroid Dose at Week 24

A new or increased dose of corticosteroids (prednisone or equivalent) from the Day 1 dose was permitted as rescue treatment. Rescue medication was to be considered if the absolute hemoglobin level continued to decline, there was a \> 1 g/dL decrease in hemoglobin from the prior assessment, or the participant developed new or worsening symptoms of wAIHA. Percentage change from Baseline was calculated as (\[the post-Baseline value minus the Baseline value\]/Baseline value) x 100.

Time frame: Baseline; Week 24

Percentage of Participants Who Required Rescue Therapy at Any Visit From Week 6 Through Week 24, and From Week 24 to Week 48

Rescue medication was to be considered if the absolute hemoglobin level continued to decline, there was a \> 1 g/dL decrease in hemoglobin from the prior assessment, or the participant developed new or worsening symptoms of wAIHA.

Time frame: Week 6 to Week 24; Week 24 to Week 48

Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. TEAEs were defined as AEs reported for the first time or the worsening of pre-existing events after the first dose of study drug.

Time frame: up to 446 days

Number of Participants With Any ≥Grade 3 TEAE

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. TEAEs were defined as AEs reported for the first time or the worsening of pre-existing events after the first dose of study drug. The severity of AEs were assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.

Time frame: up to 446 days