A positron emission tomography (PET) study to assess where the radiotracer [11C]AZ14132516 goes in the body following administration to healthy participants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB, AstraZeneca AB

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]

Trial duration

27 Apr 2023 → 11 Jul 2023

Decision date (initial)

2023-04-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To examine the distribution of [11C]AZ14132516 and binding to CCR9 in anatomical regions of interest (in abdominal area)

Secondary objectives 2

1. To assess the reproducibility of [11C]AZ14132516 binding parameters.
2. To assess the safety of [11C]AZ14132516 following intravenous administration of single and repeat doses

Conditions and MedDRA coding

Crohn's disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Capable of giving signed informed consent as described in Appendix A, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
2. Able and willing to participate in all scheduled evaluations, abide by all study restrictions, and complete all required tests and procedures.
3. Participants ≥ 20 to 65 years of age inclusive, at the time of signing the ICF.
4. Participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory parameters and ECG performed before first administration of investigational product.
5. Body weight within 50.0 to 100.0 kg and body mass index within the range 18.0 to 30.0 kg/m2 (inclusive).
6. Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a) Female participants:  WOCBP must have a negative pregnancy test at screening and before PET examination (all premenopausal women, or in case when menstrual status cannot be ascertained in women under the age of 55 years).  If sexually active with a non-sterilised male partner, must use at least one highly effective method of birth control during the study period and for 7 days following last radioligand administration.  It is strongly recommended that non-sterilised male partners of female participants of childbearing potential use a male condom plus spermicide during the study period. Female participants must not breastfeed and must not donate or retrieve ova for their own use during the study period and for 7 days following last radioligand administration. b) Male participants:  Non-sterilised male participants who are sexually active with a female partner of childbearing potential must use a condom with spermicide during the study period and for 7 days following last radioligand administration. It is strongly recommended that female partners of male participants also use at least one highly effective method of contraception throughout this period. In addition, male participants must refrain from fathering a child or donating sperm during the study period and for 7 days following last radioligand administration.

Exclusion criteria 17

1. Current significant major or unstable respiratory disease, heart disease, cerebrovascular disease, hematological disease, hepatic disease, renal disease, gastrointestinal disease, or other major diseases.
2. Participants with unstable hypertension (as judged by the Investigator) or symptomatic hypotension, history of pre-syncope or syncope due to orthostatic hypotension and/or induced by change of posture (orthostatic hypotension defined as 25 mmHg decrease in systolic and/or 15 mmHg).
3. Significant abnormalities on the clinical examination, including neurological and physical examination, vital signs, ECG and clinical.
4. Chemistry, hematology, or urine analysis results that may interfere with the study or present a safety risk to the patient.
5. Abnormal vital signs, after 10 minutes of supine rest as judged by the PET centre physician. As a guide, any readings outside the following should be considered in the evaluation: a) systolic blood pressure (BP) ≥ 140 mmHg b) diastolic BP ≥ 90 mmHg c) heart rate ≤ 35 bpm or ≥ 100 bpm The inclusion of participants meeting the above criteria may be decided on a case-by case basis by PET centre physician.
6. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. This may include participants with any of the following: (a) PR (PQ) interval prolongation of clinical significance as judged by the Investigator (b) Intermittent second or third degree AV block (AV block II Mobitz type 1, Wenchebach, while asleep or in deep rest is not disqualifying) (c) Incomplete, full, or intermittent bundle branch block (QRS ≤ 110 ms with normal QRS and T wave morphology is acceptable if there is no evidence of left ventricular hypertrophy) (d) Abnormal T wave morphology, particularly in the protocol-defined primary lead (e) Prolonged QTcF ≥ 470 ms or shortened QTcF 340 ms or a family history of long QT syndrome. The inclusion of participants meeting the above criteria may be decided on a case-by case basis by PET centre physician.
7. Known or suspected systemic infection (eg, hepatitis B virus, hepatitis C virus, HIV and tuberculosis), including previous or ongoing infectious or autoimmune disease.
8. Participants must abstain from taking prescription or non-prescription drugs (including vitamins, recreational drugs, and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study intervention until completion of the follow-up visit, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study.
9. Current drug abuse or dependence or positive screen for drugs of abuse at screening visit.
10. Participants on anticoagulant treatment.
11. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
12. Suffers from claustrophobia that limits the ability to undergo the scanning procedure.
13. Participant has abnormal blood flow confirmed by a negative Allen’s test in both hands at screening.
14. Blood donation within 1 month of screening or any blood donation/blood loss greater than 500 mL during the 3 months prior to screening.
15. Positive SARS-CoV-2 rapid antigen test at screening
16. Any other reason that, in the study PI opinion, prohibits the inclusion of the participants into the study.
17. Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Standard uptake value (SUV) in region of interest; Standard uptake value ratio (SUVR) in regions of interest (ie, total binding of [11C]AZ14132516 to CCR9)

Secondary endpoints 3

1. Absolute percentage differences of total binding of [11C]AZ14132516 to CCR9 in regions of interest between two PET examinations
2. Intraclass correlation coefficients
3. Description of any safety findings, AEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Pepparedsleden 1

City

Molndal

Postcode

431 53

Country

Sweden

Sponsor responsibilities

Article 77 compliance

AstraZeneca AB

Contact point sponsor

AstraZeneca AB

Article 77 implementation

AstraZeneca AB

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications