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

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Parsaclisib in Participants With Primary Warm Autoimmune Hemolytic Anemia

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),

Study Overview

• Status: Active, not recruiting
• Conditions: Warm Autoimmune Hemolytic Anemia (wAIHA)
• Intervention / Treatment: Drug: parsaclisinib; Drug: placebo

Detailed Description

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
• Enrollment (Actual): 13
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzburg CET, Austria, A-5020
    • Investigative Site AT002
  • Vienna, Austria, 01090
    • Investigative Site AT001
• Belgium
  • La Louviere, Belgium, 07100
    • Investigative Site BE001
  • Liege, Belgium, 04000
    • Investigative Site BE002
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2P4
      • Investigative Site CA001
• France
  • Lille Cedex, France, 59037
    • Investigative Site FR002
  • Marseille, France, 13285
    • Investigative Site FR003
  • Paris, France, 75015
    • Investigative Site FR001
• Germany
  • Essen, Germany, 45147
    • Investigative Site DE001
  • ULM, Germany, 89081
    • Investigative Site DE002
• Israel
  • Haifa, Israel, 31096
    • Investigative Site IL002
  • Nahariya, Israel, 2210001
    • Investigative Site IL001
• Italy
  • Firenze, Italy, 50134
    • Investigative Site IT003
  • Milan, Italy, 20122
    • Investigative Site IT002
  • Novara, Italy, 28100
    • Investigative Site IT001
  • Pavia, Italy, 27100
    • Investigative Site IT004
  • Rome, Italy, 00168
    • Investigative Site IT006
  • Trieste, Italy, 34125
    • Investigative Site IT005
• Japan
  • Fukuoka, Japan, 807-8556
    • Investigative Site JP008
  • Isehara, Japan, 259-1193
    • Investigative Site JP004
  • Nagoya, Japan, 467-8602
    • Investigative Site JP006
  • Okayama, Japan, 700-8557
    • Investigative Site JP009
  • Okayama, Japan, 701-0192
    • Investigative Site JP002
  • Osakasayama-shi, Japan, 589-8511
    • Investigative Site JP010
  • Saitama, Japan, 350-0495
    • Investigative Site JP005
  • Sendai-shi, Japan, 980-8574
    • Investigative Site JP007
  • Suita-shi, Japan, 565-0871
    • Investigative Site JP001
  • Tokyo, Japan, 141-8625
    • Investigative Site JP003
• Netherlands
  • Rotterdam, Netherlands, 3015CA
    • Investigative Site NL001
• Poland
  • Legnica, Poland, 59220
    • Investigative Site PL001
  • Lodz, Poland, 93-510
    • Investigative Site PL006
  • Nowy Sacz, Poland, 33-300
    • Investigative Site PL003
  • Opole, Poland, 45-372
    • Investigative Site PL005
  • Walbrzych, Poland, 58-309
    • Investigative Site PL004
  • Wroclaw, Poland, 53-439
    • Investigative Site PL002
• Spain
  • Badalona, Spain, 08916
    • Investigative Site ES006
  • Barcelona, Spain, 08036
    • Investigative Site ES001
  • Madrid, Spain, 28006
    • Investigative Site ES003
  • Murcia, Spain, 30008
    • Investigative Site ES005
  • Tarragona, Spain, 43005
    • Investigative Site ES004
  • Valencia, Spain, 46026
    • Investigative Site ES002
• United Kingdom
  • Glasgow, United Kingdom, G4 0SF
    • Investigative Site GB002
  • London, United Kingdom, W12 0HS
    • Investigative Site GB006
  • Norwich, United Kingdom, NR4 7UY
    • Investigative Site GB003
  • Plymouth, United Kingdom, PL6 8DH
    • Investigative Site GB004
  • Reading, United Kingdom, RG1 5AN
    • Investigative Site GB005
• United States
  • California
    • Los Angeles, California, United States, 90089
      • Investigative Site US005
    • Whittier, California, United States, 90603
      • Investigative Site US004
  • Florida
    • Miami, Florida, United States, 33165
      • Investigative Site US006
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Investigative Site US012
  • New York
    • Bronx, New York, United States, 10461
      • Investigative Site US007
    • Bronx, New York, United States, 10467
      • Investigative Site US002
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • Investigative Site US003
  • Ohio
    • Canton, Ohio, United States, 44718
      • Investigative Site US009
  • Pennsylvania
    • Easton, Pennsylvania, United States, 18045
      • Investigative Site US010
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Investigative Site US001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Parsaclisib; Participants will receive parsaclisib for 24 weeks (double-blind period). Participant who completed the double-blind period and tolerating the study treatment upon investigator's opinion will continue into open-label period for an additional 24 weeks. Participants may then continue to receive parsaclisib in a long-term extension period.	Drug: parsaclisinib; parsaclisib will be administered QD orally; Other Names: INCB050465
Placebo Comparator: Group B: Placebo followed by Parsaclisib; Participants will receive placebo for 24 weeks (double-blind period). Participants who completed the double-blind period will receive parsaclisib in the 24 week open-label period. Participants may then continue to receive parsaclisib in a long-term extension period.	Drug: placebo; placebo will be administered QD orally follwed by Parsaclisinib in the open label period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants attaining a durable hemoglobin response	Proportion of participants attaining a durable hemoglobin response, defined as hemoglobin ≥ 10 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.	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with a ≥ 3-point increase in FACIT-F score	Increase is measured by Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire. 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.	Up to Week 24
Proportion of participants with a 50 m increase in a 6MWT	Defined as an increase of 50 m using the Six-minute walk test, a self-paced measurement of the distance that a participant can quickly walk on a flat, hard surface in a period of 6 minutes.	Up to Week 24
Change in FACIT-F score	Change will be measured by Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire. 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.	Up to 3 years
Percent Change in FACIT-F	will be measured by Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire. 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.	Up to 3 years
Change in hemoglobin	Changes will be measured and compared in the hematology panel.	Up to 3 years
Percentage change in hemoglobin	Percentage change will be measured and compared in the hematology panel.	Up to 3 years
Proportion of participants who received transfusions	Proportion of participants who received transfusions.	Up to 48 weeks
Change in corticosteroid dose from baseline	Change from baseline of daily corticosteroids dose	Up to Week 24
Percentage change from baseline in daily corticosteroid dose	Percentage change from baseline of daily corticosteroids dose	Up to Week 24
Proportion of participants who required rescue therapy at any visit	Rescue therapy will include new/increased dose of corticosteroids, transfusions, intravenous immunoglobulin (IVIG), and Erythropoietin.	Up to 48 weeks
Number of Participants with Treatment Emergent Adverse Events (TEAE)	Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.	Up to 3 years

Collaborators and Investigators

• Sponsor: Incyte Corporation
• Investigators: Study Director: Kathleen Butler, MD, Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2022
• Primary Completion (Actual): October 17, 2023
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: September 28, 2021
• First Submitted That Met QC Criteria: September 29, 2021
• First Posted (Actual): October 11, 2021

Study Record Updates

• Last Update Posted (Actual): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Warm Autoimmune Hemolytic Anemia (wAIHA)
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: INCB 50465-309

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

• IPD Sharing Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• IPD Sharing Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No