Allergic esophagus inflammation Coeliac disease Gluten intolerance
Conditions
Interventions
Subjects in Cohorts B1 (70 mg dose) and B2 (210 mg dose) will receive the study
drug (CALY-002 or placebo) IV once every 2 weeks (q2w) for 8 weeks (2 × 28-day
treatment cycles
a total of 4 doses).
All subjects in cohort C1 will receive IV administration of CALY-002 at a
currently planned dose of 210 mg q2w for 12 weeks (3 × 28-day treatment cycles
a total of 6 study drug administrations).
Sponsors
Calypso Biotech BV
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: For inclusion in Part B of the study, a subject with CeD should meet all of the following criteria: 1. Subject is a male or female >= 18 years of age, at the time of signing the ICF. 2. Subject has a BMI between > 17.5 and 1.5 and CD3+ IEL density < 40 cells/100 villus enterocytes. 6. Subject must have been on a GFD for at least 12 consecutive months prior to screening and will have to remain on a GFD for the duration of study participation (during the 8-week gluten challenge, subjects will consume approximately 3 g of gluten daily while continuing with their GFD). 7. Subject must have negative anti-tissue transglutaminase (tTG) immunoglobulin A (IgA) serology at screening. Note: At primary diagnosis of CeD, subjects should have had a Marsh score of at least IIIA/B/C and either the existence of positive TG-IgA serology that became negative upon GFD or clinical improvement after introduction of GFD. If no TG-IgA serology was done at the first diagnosis, then the investigator should contact the medical monitor and discuss subject eligibility. 8. Subject must have human leukocyte antigen (HLA) genotype DQ2 or DQ8 as confirmed by medical records. 9. Subject must be willing to undertake a gluten challenge (ie, intake of approximately 3 g of gluten daily) for 56 consecutive days (8 weeks) during the Treatment Period. Note: This will be the only allowed intake of gluten while subjects need to remain on their GFD throughout study participation. 10. Subject must be healthy on the basis of physical examination findings, clinical laboratory tests, medical history, vital signs, and cardiac monitoring (normal 12-lead ECG results) performed at screening, in the opinion of the investigator. 11. An FCBP must either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation or intrauterine device; barrier contraceptive with spermicide; or vasectomised partner), one of which must be a barrier method, from the time of signing the ICF through EOS. In addition, an FCBP must have two negative pregnancy tests as verified by the investigator prior to receiving the first dose: • A negative serum FSH and β-HCG pregnancy test at screening. • A negative urine pregnancy test prior to randomisation on Day 1. 12. A male subject must practice true abstinence or agree to use a condom (a latex condom is recommended) during sexual contact with a pregnant female or an FCBP and will avoid conceiving from the time of signing the ICF through EOS, even if he has undergone a successful vasectomy.<br
Exclusion criteria
Exclusion criteria: A subject with CeD will not be eligible for inclusion in Part B of this study if any of the following criteria apply: 1. Subject has a concurrent active autoimmune disease (other than CeD) that requires systematic treatment with immunosuppressants. Note: Inclusion of subjects with a history of autoimmune disease without symptoms or treatment for more than 3 years or subjects with autoimmune thyroiditis that is well controlled with levothyroxine substitutions can be discussed with the medical monitor. 2. Subject has severe complication of CeD such as refractory CeD. 3. Subject has active dermatitis herpetiformis. 4. Subject has active (microscopic) colitis with clinical signs of diarrhoea and abdominal pain. 5. Subject has any significant medical condition (including but not limited to neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, haematological, drug allergies, or other major disorders), laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 6. Subject has any condition that confounds the ability to interpret data from the study. 7. Subject is pregnant or breastfeeding. 8. Subject is currently receiving or has been previously treated with a biologic agent. Exception: If prior treatment with the biologic agent was completed at least 6 months prior to the first dose, the medical monitor can be consulted for potential recruitment. 9. Subject has a history of anaphylactic reactions to protein therapeutics. 10. Subject has evidence of SARS-CoV-2 infection and/or subject has not been fully vaccinated for COVID-19 (according to the vaccine's local summary of product characteristics) at least 2 weeks before screening and/or subject is deemed at risk for the coronavirus disease (COVID19) in the opinion of the treating physician or the subject has participated in another clinical study involving treatment(s), which may increase such risk. 11. Subject has participated or is planning to participate in another investigational drug study within 60 days prior to the first dose. 12. Subject has malignancy or prior malignancy, with a disease free interval of < 5 years after diagnosis and intervention, except for curative treatment for non-melanoma skin cancer or resected carcinoma in situ. 13. Subject has current or recent (within 4 weeks prior to screening) signs or symptoms of infection that require parenteral antibiotic administration. 14. Subjects has a hepatitis B infection (confirmed by HBsAg), hepatitis C infection (confirmed by HCV RNA testing), or HIV 1 or HIV-2 antibodies or infection at screening. 15. Subject has had major surgery (including joint surgery) within 8 weeks prior to screening and hospitalisation for a clinically relevant event within the 4 weeks prior to screening. 16. Subject has received immunisation with a live or live attenuated vaccine within 60 days prior to the first dose or is planning to receive immunisation with a live or live attenuated vaccine within 60 days after the last dose. 17. Subject has been committed to an institution by way of official or judicial order. 18. Subject has used any new prescription or experimental drugs (including biologics/monoclonal antibodies) for the treatment of their coeliac disease 30
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part B: Primary: To assess the safety and tolerability of CALY-002 following multiple ascending doses administered IV in subjects with coeliac disease (CeD). Part C: Primary: To assess the safety and tolerability of CALY-002 following multiple IV administration in subjects with eosinophilic oesophagitis (EoE). | — |
Secondary
| Measure | Time frame |
|---|---|
| Part B: Secondary: (1) To characterise the PK of CALY-002 following multiple ascending doses administered IV in subjects with CeD; (2) To investigate the immunogenicity of CALY-002 following multiple ascending doses administered IV in subjects with CeD. Part C: Secondary: (1) To characterise the PK of CALY-002 following multiple IV administration in subjects with EoE; (2) To investigate the immunogenicity of CALY-002 following multiple IV administration in subjects with EoE. | — |
Countries
Netherlands
Outcome results
None listed