Warm Antibody Autoimmune Hemolytic Anemia
Conditions
Brief summary
Phase II Study: To evaluate the safety and preliminary efficacy of HMPL-523 in adult patients with wAIHA. Phase III Study(Part A): Confirmation of Efficacy safety and of HMPL-523 in adult patients with wAIHA. Phase III Study (Part B): To further evaluate the long-term safety and tolerability of HMPL-523 in adult patients with wAIHA.
Detailed description
Phase II Study: An eight-week randomized, placebo-controlled, double-blind phase followed by at least a 16-week open-label HMPL-523 treatment to evaluate the safety and preliminary efficacy of HMPL-523. The primary endpoint was the proportion of patients with overall Hb response by week 24. Phase III study (Part A):A 24-week randomized, placebo-controlled double-blind phase to evaluate efficacy and safety of HMPL-523. The primary endpoint was the proportion of patients who achieve a durable response during weeks 5 to 24. Phase III Study (Part B): An open-label Phase evaluating long-term safety and efficacy of HMPL-523 treatment. Eligible patients include those with lack of efficacy during the 20-week Phase III Part A treatment, completion of the Phase II study, or completion of 24-week Phase III Part A treatment with investigators assessment of potential benefit from open-label treatment with HMPL-523.
Interventions
DRUGHMPL-523(300mg PO QD)
HMPL-523(300mg PO QD)
DRUGPlacebo
Placebo(300mg PO QD)
Sponsors
Hutchmed
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily signed the informed consent form (ICF); 2. Males or females aged 18 to 75 years; 3. Patients diagnosed with primary wAIHA or secondary wAIHA whose underlying diseases are stable; 4. Organs in good function.
Exclusion criteria
1. Patients with other types of AIHA other than wAIHA; 2. Patients with secondary wAIHA with unstable underlying disease; 3. Patients with drug-induced secondary wAIHA; 4. Patients with infections requiring systemic treatment; 5. Patients previously treated with Syk inhibitors (e.g., fostamatinib); 6. Patients with known allergy to the active ingredients or excipients of the study drug; 7. Patients with serious psychological or mental disorder; 8. Alcoholic or drug abuser; 9. Female patients who are pregnant and lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase II: Overall Hb response rate | 24Weeks | Phase II: Overall Hb response rate: The proportion of patients with overall Hb response by Week 24 |
| Phase III(Part A): Durable Hb response rate | 24Weeks | Phase III(Part A):Durable Hb response rate: The proportion of patients who achieve a durable response by Week 24 during Part A |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase II: Overall Hb response rate | 8 Weeks | Phase II: Overall Hb response rate: the proportion of patients with overall Hb response by Week 8 |
| Phase II: Durable Hb response rate | 24 Weeks | Phase II: Durable Hb response rate: the proportion of patients who achieve a durable response by Week 24. |
| Phase II: Median change in Hb | 24 Weeks | Phase II: Median change from baseline in Hb at Weeks 8 and 24 of treatment. |
| Phase II: Effects on reticulocyte count | 24 Weeks | Phase II: Change from baseline in reticulocyte count at Weeks 8 and 24 of treatment. |
| Phase II: Effects on lactate dehydrogenase | 24 Weeks | Phase II: Change from baseline in lactate dehydrogenase(LDH) at Weeks 8 and 24 of treatment. |
| Phase II: Effects on haptoglobin | 24 Weeks | Phase II: Change from baseline in haptoglobin at Weeks 8 and 24 of treatment. |
| Phase II: Effects on total bilirubin(TBIL) | 24 Weeks | Phase II: Change from baseline in total bilirubin(TBIL) at Weeks 8 and 24 of treatment. |
| Phase II: Proportion of rescue therapy | 24 Weeks | Phase II: Proportion of patients who received rescue therapy by Weeks 8 and 24 of treatment. |
| Phase II: Proportion of patients with dose reduction in baseline anti-wAIHA medications | 24 Weeks | Phase II: Proportion of patients who had a dose reduction in glucocorticoids or other baseline concomitant anti-wAIHA medications by Weeks 8 and 24 of treatment. |
| Phase II: Time to response | 24 Weeks | Phase II: Time to response |
| Phase II: Effect of study treatment on patient fatigue | 24 Weeks | Phase II: Evaluation of the effect of study treatment on fatigue at Weeks 8 and 24, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) |
| Phase II: Effect of study treatment on quality of life | 24 Weeks | Phase II: Evaluation of the effect of study treatment on quality of life at Weeks 8 and 24, as assessed by the 36-Item Short Form Health Survey (SF-36). |
| Phase III(Part A): Overall Hb response rate | 24 Weeks | Phase III(Part A): Proportion of patients who achieved an overall Hb response during the 20-week and 24-week double-blind treatment periods(defined as at least one Hb value ≥100g/L with an increase of at least 20g/L from baseline, not attributable to rescue therapy). |
| Phase III(Part A): Median change in Hb | 24 Weeks | Phase III(Part A): Median change from baseline in Hb during the 20-week and 24-week double-blind treatment periods. |
| Phase III(Part A): Effects on reticulocyte count | 24 Weeks | Phase III(Part A): Change from baseline in reticulocyte count during the 20-week and 24-week double-blind treatment periods. |
| Phase III(Part A): Effects on lactate dehydrogenase | 24 Weeks | Phase III(Part A): Change from baseline in lactate dehydrogenase(LDH) during the 20-week and 24-week double-blind treatment periods. |
| Phase III(Part A): Effects on haptoglobin | 24 Weeks | Phase III(Part A): Change from baseline in haptoglobin during the 20-week and 24-week double-blind treatment periods. |
| Phase III(Part A): Effects on total bilirubin(TBIL) | 24 Weeks | Phase III(Part A): Change from baseline in total bilirubin(TBIL) during the 20-week and 24-week double-blind treatment periods. |
| Phase III(Part A): Proportion of rescue therapy | 24 Weeks | Phase III(Part A): Proportion of patients who received protocol-defined rescue therapy during the 20-week and 24-week double-blind treatment periods. |
| Phase III (Part A): Proportion of patients reducing or discontinuing baseline anti-wAIHA medications | 24 Weeks | Phase III(Part A):The proportion of patients who reduced or discontinued glucocorticoids or other baseline concomitant anti-wAIHA medications during the 20-week and 24-week double-blind treatment periods. |
| Phase III(Part A): Time to first response | 24 Weeks | Phase III(Part A): Time to first response |
| Phase III(Part A): Duration of durable response | 24 Weeks | Phase III(Part A): Duration of durable response |
| Phase III(Part A): Cumulative duration of response | 24 Weeks | Phase III(Part A): Cumulative duration of response |
| Phase III(Part A): Effect of study treatment on patient fatigue | 24 Weeks | Phase III(Part A): Effect of study treatment on patient fatigue during the 20-week and 24-week treatment periods, as assessed by the FACIT-F score (40 items; range, 0-160), including the FACIT-Fatigue subscale (13 items; range, 0-52). |
| Phase III(Part A): Effect of study treatment on patients' quality | 24 Weeks | Phase III(Part A): Effect of study treatment on patients' quality of life during the 20-week and 24-week treatment periods, as assessed by SF-36. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORFengkui Zhang, professor
offices director
Outcome results
None listed