LOU064

Study Description

The purpose of this Phase 2 study is to evaluate the efficacy, safety, and tolerability of oral remibrutinib (LOU064) at doses of 10 mg BID, 25 mg BID, 100 mg BID for one month (4-5 weeks), and oral remibrutinib 25 mg BID for 1 week compared to placebo in adult participants (age 18-55 years, inclusive). Assessments will serve to measure protection against allergic reaction by measuring the decrease of sensitivity (e.g.: signs and symptoms of allergic reaction) to oral peanut allergen administered in a double-blind, placebo-controlled food challenge (DBPCFC). Participants will have medically confirmed peanut allergy. Data from this study will be used to support the registration of remibrutinib use in the food allergy population to protect against allergic reactions due to an accidental exposure to peanut.

Study Eligibility

Inclusion criteria

Participants eligible for inclusion in this study must meet all of the following criteria:

1. Signed informed consent must be obtained prior to study participation. Participants must be able to understand and provide informed consent.
2. Male or female participants who are 18 to 55 years of age, inclusive, at the time of signing informed consent.
3. Documented medical history of allergy to peanuts or peanut-containing foods.
4. Positive peanut-specific IgE (peanut sIgE), ≥ 6 kUA/L at Screening Visit 1.
5. Positive skin prick test (SPT) for peanut allergen at Screening Visit 1. This is defined as the average diameter (longest diameter and mid-point orthogonal diameter) ≥ 3 mm wheal compared to the negative control.
6. A positive peanut DBPCFC during screening (Screening Visits 2 and 3). A positive peanut result is defined as the occurrence of dose-limiting symptoms at a single dose ≤ 100 mg of peanut protein during the screening DBPCFC.
7. Participants must be able to comply with treatment regimen, participate in the DBPCFC, and must be willing to continue avoiding exposure to peanuts and any other foods that they are allergic to throughout this study.

Exclusion criteria

Participants meeting any of the following criteria are not eligible for inclusion in this study.

1. Previous use of remibrutinib or other BTK inhibitors.
   
   
2. Use of other investigational drugs within 5 half-lives or within 30 days (for small molecules) prior to Screening Visit 1, or until the expected pharmacodynamic (PD) effect has returned to baseline (for biologics), whichever is longer; or longer if required by local regulations.
   
   
3. History of hypersensitivity to any of the following:
• study drug or its excipients or to drugs of similar chemical classes
• hypersensitivity or intolerance to any of the matrix components used within the material for the DBPCFC (please refer to the LOU064I12201 Pharmacy Manual forthe preparation of the DBPCFC material and for details on the material components)
  
  
4. History of severe or life-threatening hypersensitivity event leading to ICU (intensive care unit) admission or intubation within 60 days prior to Screening Visit 1. 
   
   
5. Any occurrence of dose-limiting symptoms to placebo allergen at screening DBPCFC (determined after unblinding of DBPCFC from Screening Visits 2 and 3, described in Section 6.4.2). 
   
   
6. Participants with uncontrolled asthma (according to GINA guidelines, GINA 2021) who meet any of the following criteria:
   • FEV1 < 80% of participant's predicted normal value at Screening Visit 1
   • Hospitalization for asthma within 12 months prior to Screening Visit 1
     
     
7. Current or previous history of a mast cell disorder, including mastocytosis, or tryptase ≥ 20 ng/ml at Screening Visit 1. 
   
   
8. Have received any live or live-attenuated vaccines (including but not limited to varicella zoster virus or measles, oral polio, nasal influenza) within 6 weeks prior to randomization or requirement to receive these vaccinations less than 4 weeks after the last study drug dose. Refer to Section 4.5 for statement on vaccine administration. 
   
   
9. History of major surgery within 8 weeks prior to Screening Visit 1, and/or planning or expecting to have surgery during the study or up to 30 days after the last dose. 
   
   
10. Use of prohibited medication within the interval defined (Table 6‐4) prior to treatment randomization (Day 1). 
    
    
11. Any clinically significant disease that, in the opinion of the investigator, would put the safety of the patient at risk through participating, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study, or would compromise patient compliance or preclude completion of the study. 
    
    
12. History of malignancy of any organ system within 5 years of Screening Visit 1 [except for basal cell carcinoma; actinic keratoses; Bowen disease (carcinoma in situ) that have been treated, with no evidence of recurrence in the past 12 weeks prior to Screening Visit 1; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed]. 
    
    
13. Presence of clinically significant cardiovascular conditions such as but not limited to myocardial infarction, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to screening.
    
    
14. History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants participating in the study such as:
    • Resting QTcF ≥ 450 msec (male) or ≥ 460 msec (female) at Screening Visit 1.
    • Concomitant clinically significant cardiac arrhythmias, e.g. atrial fibrillation,
    sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker
    • History of familial long QT syndrome or known family history of Torsades de Pointe, cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III anti-arrhythmic drugs
      
      
15. History of significant bleeding risk or coagulation disorders. 
    
    
16. Participants with screening hematology parameters below the following thresh-holds will be excluded:
    
    • Hemoglobin: < 10 g/dl
    • Platelets: < 100,000/mm3
    • Leucocytes: < 3,000/mm3
    • Neutrophils: < 1,500/mm3
17. Requirement for anticoagulant medication [for example, warfarin or Novel Oral Anti-Coagulants (NOAC)]. 
    
    
18. Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel. The use of dual anti-platelet therapy (e.g. acetylsalicylic acid + clopidogrel) is prohibited. 
    
    
19. History of gastrointestinal bleeding, e.g. in association with use of nonsteroidal anti-inflammatory drugs (NSAID), that was clinically relevant (e.g. where intervention was indicated or requiring hospitalization or blood transfusion). 
    
    
20. Patients with history of splenectomy. 
    
    
21. Known or suspected ongoing, chronic or recurrent infectious disease including but not limited to tuberculosis, atypical mycobacterioses, listeriosis, aspergillosis, or endemic mycoses, and/or known positivity for human immunodeficiency virus (HIV) infection. HIV antibody tests will be performed to determine HIV status with follow-up testing/reporting as required by local regulation. 
    
    
22. Active systemic bacterial, viral, parasitic or fungal infection that are, in the opinion of the investigator, clinically significant, including but not limited to infections requiring hospitalization or IV antibiotics. 
    
    
23. Evidence of an ongoing hepatitis C infection (e.g. defined by the detection of hepatitis C ribonucleic acid (HCV-RNA) at screening) and/or an ongoing hepatitis B infection (defined by the detection of hepatitis B virus surface antigen (HBsAg) and/or hepatitis B virus (HBV)-DNA at screening; participants who are positive for anti-hepatitis B core (HBc) antibodies but who are negative for antibodies against HBsAg and HBV-DNA can be included into the study if they agree to monitoring for HBsAg and HBV-DNA reactivation). 
    
    
24. Active, chronic disease of the immune system (including stable disease treated with immune therapy, e.g. rheumatoid arthritis, systemic lupus erythematosus, etc.) with the exception of well-controlled diabetes or thyroid disorder. 
    
    
25. History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) or International Normalized Ratio (INR) of more than 1.5 at screening. 
    
    
26. History of renal disease, creatinine level above 1.5x ULN, or estimated Glomerular Filtration Rate (eGFR) <45ml/min (using the Cockcroft-Gault equation) at screening. 
    
    
27. History or evidence of ongoing alcohol or drug abuse, within the last 6 months prior to screening. 
    
    
28. Pregnant or nursing (lactating) females. 
    
    
29. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for at least 2 weeks after stopping study medication. Highly effective contraception methods include:
    
    
    
    • Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
    • Female bilateral tubal ligation, female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
    • Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.
    • Use of oral, (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). Women are considered not of childbearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks prior to enrollment on study. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If local regulations are more stringent than the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF. 
      
      
30. Patients who, in the opinion of the Investigator, will not be able to comply with study procedures or visits, adhere to dosing schedule, or other otherwise be in compliance with study requirements.

Contact Information

Phone: 501-364-3886
Email: whitesided@archildrens.org