Depemokimab in participants with hypereosinophilic syndrome, efficacy and safety trial

JRCT ID: jRCT2051220052

Registered date:18/06/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: 18-year-old or older patients with hypereosinophilic syndrome (HES)
• Date of first enrollment: 01/07/2022
• Target sample size: 12
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,China,Japan,Czechia,Japan,Denmark,Japan,France,Japan,Germany,Japan,Greece,Japan,Hong Kong,Japan,Israel,Japan,Italy,Japan,Mexico,Japan,Poland,Japan,Portugal,Japan,Romania,Japan,South Korea,Japan,Spain,Japan,Switzerland,Japan,UK,Japan,US,Japan
• Study type: Interventional
• Intervention(s): In the depemokimab group, depemokimab. In the placebo group, placebo of depemokimab will be administered. The subjects are randomized in a 2:1 ratio to receive either depemokimab or placebo.

Outcome(s)

• Primary Outcome: Frequency of HES flares during the 52-week study intervention period

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Participant must be >= 18 years of age, at the time of signing the informed consent.
Body weight
2. Participants who are >= 40 kg at Screening Visit 1.
Type of Participant and Disease Characteristics
3. Participants who have a documented diagnosis of HES prior to Visit 2. HES diagnosis is based on:
- blood eosinophilia of >1500 eosinophils/microL on at least 2 occasions at >= 1-month interval, without a discernible non-haematological secondary cause, and
- signs or symptoms of organ involvement and/or dysfunction that can be directly related to eosinophilia.
4. Flare history: A history of 2 or more HES flares within the past 12 months prior to Visit 1. Historical HES flares are defined as documented HES-related worsening of clinical symptoms or blood eosinophil counts requiring an addition or escalation in OCS or cytotoxic/immunosuppressive therapy. At least one HES flare within the past 12 months must not be related to a decrease in HES therapy during the 4 weeks prior to the flare.
Sex and Contraceptive/Barrier Requirements
5. Male or female participants
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
- Is a woman of non-childbearing potential (WONCBP) OR
- Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, from at least 14 days prior to the first dose of study intervention until at least 30 weeks after the last administered dose of study intervention. The Investigator should evaluate the potential for contraceptive method failure (e.g., non-compliance, recently initiated) in relationship to the first dose of study intervention.
- A WOCBP must have a negative highly sensitive serum pregnancy test at Screening Visit 1 and a negative highly sensitive urine pregnancy test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- The Investigator should evaluate the potential for contraceptive method failure (e.g., non-compliance, recently initiated in relationship to the first dose of study intervention.
- The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Informed Consent
6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. HES disease manifestations which in the opinion of the Investigator may put the participant at unacceptable risk from study participation or confound interpretation of efficacy or safety data. Specific consideration should be given to the participants ability to comply with protocol requirements, including the list of prohibited therapies; exclusion criteria no. 14 - 16.
2. Infection:
- Participants with chronic or ongoing active infections requiring systemic treatment.
- Participants with a pre-existing parasitic infestation within 6 months prior to Visit 1.
3. Immunodeficiency: Participants with a known immunodeficiency (e.g., Human Immunodeficiency Virus [HIV]), other than that explained by the use of OCS or other therapy taken for HES.
4. Malignancy:
- Participants with a history of or current lymphoma.
- Participants with current malignancy or previous history of cancer in remission for less than 5 years prior to Visit 1. Participants that had localized carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded.
- Participants with a haematologic malignancy with hypereosinophilia in which HES is not the primary diagnosis, e.g., chronic myeloid leukaemia, myelodysplastic syndrome, chronic eosinophilic leukaemia-not otherwise specified.
5. Liver disease:
- Cirrhosis or current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice.
NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C) are acceptable if participant otherwise meets entry criteria.
6. Cardiovascular: Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
7. Vasculitis: Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at Screening will be evaluated and current vasculitis must be excluded prior to randomization.
8. Eosinophilia of unknown significance: Hypereosinophila with no clinical symptoms and/or proof of organ dysfunction.
9. Clinical diagnosis of EGPA.
10. Coronavirus disease 2019 (COVID-19): Participants that, according to the Investigators medical judgment, are likely to have active COVID-19 infection should be excluded. Participants with known COVID-19 positive contacts within the past 14 days must be excluded for at least 14 days following the exposure during which the participant must remain symptom-free.
11. Other concurrent medical conditions that may affect the participants safety: Participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, cardiac or any other system abnormalities that are not associated with HES and are uncontrolled with standard treatment.
12. Hypersensitivity: Participants with an allergy/ intolerance to a monoclonal antibody or biologic, or any of the excipients of the investigational product in the protocol.
Prior/Concomitant Therapy
13. Monoclonal antibodies (mAbs) targeting IL-5/5R: Participants who have a previous documented failure with anti-IL-5/5R therapy.
14. mAbs: Participants who have received mAb within 30 days or 5 half-lives, whichever is longer, prior to Visit 1. If a participant has been treated with and responsive to biologics for HES, the participant should not stop the treatment for study eligibility purpose.
15. Non-oral systemic corticosteroids: Participants who have received intravenous, intramuscular, or subcutaneous corticosteroids within 4-weeks prior to Visit 2.
16. Investigational medications/clinical study:
- Participants who have received treatment with an investigational agent within 30 days or 5 drug half-lives whichever is longer, prior to Visit 1. The term investigational applies to any drug not approved for sale in the country in which it is being used or investigational formulations of marketed products.
- Participants who are currently participating in any other interventional clinical study.
Note: Any COVID-19 vaccine approved by local government is permitted. Experimental COVID-19 vaccines are not permitted.
Diagnostic Assessments
17. FIP1L1-PDGFR alpha Status: Participants who test positive for the FIP1L1-PDGFR alpha fusion gene. Blood sampling is required for all participants at Screening (Visit 1) for this test unless the documented result is available.
18. ECG Assessment: QTcF >= 450 msec or QTcF >= 480 msec for participants with Bundle Branch Block at Screening Visit 1.
Other Exclusions
19. OCS responsiveness: Participants who are not responsive to OCS based on clinical response or blood eosinophil counts in the opinion of the Investigator.
20. Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
21. Pregnancy: Participants who are pregnant or breastfeeding. Participants must not be randomized if they plan to become pregnant during the time of study participation.
22. Adherence: Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physicians recommendations.

Related Information

• Primary Sponsor: Fujii Katsuya
• Secondary ID(s): NCT05334368