A MULTICENTRE, SAD, AND MAD CLINICAL TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF IV TREATMENT OF CALY-002 IN HEALTHY SUBJECTS AND SUBJECTS WITH COELIAC DISEASE AND EOSINOPHILIC OESOPHAGITIS

Recruiting

Conditions: Allergic esophagus inflammation
Coeliac disease
Gluten intolerance
Eosinophilic oesophagitis
10017943

Registration Number: NL-OMON52682

Lead Sponsor: Calypso Biotech BV

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 6

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 < 35.0 kg/m2 (both inclusive).
3. Subject must be willing to consent to all study-related procedures and
visits, including a minimum of 2 endoscopy procedures with small intestine
biopsies during study participation. Subject must have signed an ICF indicating
that he/she understands the purpose of and procedures required for the study
and is willing to participate in the study.
4. Subject must have a diagnosis of CeD by intestinal biopsy at least 12 months
prior to screening as confirmed by medical records.
5. Subject must have no histological signs of active CeD at screening as
confirmed by a screening intestinal biopsy, with a VH:CD ratio > 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

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Part B:<br /><br>Primary: To assess the safety and tolerability of CALY-002 following multiple<br /><br>ascending doses administered IV in subjects with coeliac disease (CeD).<br /><br><br /><br>Part C:<br /><br>Primary: To assess the safety and tolerability of CALY-002 following multiple<br /><br>IV administration in subjects with eosinophilic oesophagitis (EoE). </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Part B:<br /><br>Secondary:<br /><br>(1) To characterise the PK of CALY-002 following multiple ascending doses<br /><br>administered IV in subjects with CeD;<br /><br>(2) To investigate the immunogenicity of CALY-002 following multiple ascending<br /><br>doses administered IV in subjects with CeD.<br /><br><br /><br>Part C:<br /><br>Secondary:<br /><br>(1) To characterise the PK of CALY-002 following multiple IV administration in<br /><br>subjects with EoE;<br /><br>(2) To investigate the immunogenicity of CALY-002 following multiple IV<br /><br>administration in subjects with EoE. </p><br>