A Phase 1 Study to Investigate Safety, Tolerability, and Pharmacokinetics of CK-0045 in Healthy Participants and Otherwise Healthy Participants With Obesity

Study Overview
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Brief Summary
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The goal of this clinical trial is to assess the safety, tolerability and blood levels following a single dose or after multiple doses of CK-0045 given subcutaneously to healthy participants or otherwise healthy participants with obesity. 76 participants will receive CK-0045 or matching placebo at different escalating doses in 2 study parts: 40 healthy participants will receive a single dose and 36 otherwise healthy participants with obesity will receive 6 doses one week apart.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Investigate Safety, Tolerability, and Pharmacokinetics of CK-0045 Following Subcutaneous Administration in Healthy Participants and Otherwise Healthy Participants With Obesity

Conditions
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Healthy

Intervention / Treatment
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* Drug: CK-0045
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For non-vasectomized men with partners who are women of child bearing potential (WOCBP) and for WOCBP, highly effective contraception for 3 months. For all female participants: a negative serum (β-hCG) pregnancy test at screening and a negative urine pregnancy test on Day -1. In the opinion of the investigator, healthy based on medical history, physical and neurological examination, vital signs, and ECG, and clinical chemistry, hematology, coagulation, and urinalysis. A body weight in the range of 50 to 100 kg and a body mass index (BMI) of 18.5 to 27.0 kg/m2, inclusive, at screening for the SAD part and a BMI of 30.0 to 39.9 kg/m2, inclusive, at screening for the MAD part. A systolic blood pressure of ≥91 and ≤140 mmHg (SAD) / ≤145 mmHg (MAD) , a diastolic blood pressure of ≥51 and ≤80 mmHg (SAD) / ≤90 mmHg (MAD), and a pulse rate of ≥45 and ≤100 bpm at screening and Day 1 predose. Negative COVID-19 test (PCR) and no clinical symptoms of corona on Day -1. Signed informed consent form. Willing to adhere to the prohibitions and restrictions specified in the protocol. Exclusion Criteria: Currently have or have a history of any clinically significant medical illness or medical disorders the investigator considers should exclude the participant. Have one or more clinical laboratory test values outside the normal range at screening or on Day -1 (exceptions apply to MAD for fasting glucose, triglycerides, total cholesterol and liver enzymes). Has a QTcF interval >430 ms at screening or Day 1 predose for the SAD part or has a QTcF interval >450 ms (for male participants) or >470 ms (for female participants) at screening or Day 1 predose for the MAD part. Have a clinically significant or chronic infection or diagnosed latent infection. Significant acute illness within 7 days prior to the (first) study drug administration or have had a major illness or hospitalization within 1 month prior to the (first) study drug administration. Any history of clinically relevant skin diseases including but not limited to: Psoriasis, vitiligo, atopic dermatitis, eczema. History of any malignancy. Tattoos present on place of injection site. Major or traumatic surgery within 6 months of screening. Any participant who plans to undergo elective surgery within 4 weeks prior to the (first) study drug administration and through the end of the study. Positive serology test for HIV type 1 and 2 antibodies, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies at screening. Recent history (within 6 months from screening) of alcohol or drug abuse. Active smoker and/or has used nicotine or nicotine-containing products (including e cigarettes or the equivalent of e-cigarettes) within the past 6 months of the (first) study drug administration. A positive urine toxicology screen at screening or Day -1 for substances of abuse. Have a positive alcohol breath test at screening or Day -1. Consumes, on average, more than approximately 500 mg/day of caffeine at screening for the SAD part or consumes, on average, more than approximately 700 mg/day of caffeine at screening for the MAD part. Donated blood within 90 days prior to (first) study drug administration. Trains/exercises intensively, e.g., for a marathon or triathlon, or at a competitive level. Have a history of active drug and/or food allergy or other active allergic disease requiring the constant use of medications, or a history of severe allergic reaction, angioedema or anaphylaxis at screening. Received any experimental therapy or new investigational agent within 30 days or 5 half-lives (whichever is longer) of the (first) study drug administration. Treatment with over-the-counter medications, and herbal medication within 14 days or prescription medications within 14 days or 5 half-lives (whichever is longer) prior to (first) study drug administration and through the end of the study, unless approved by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single ascending dose (SAD) CK-0045 Dose level 1 to 5<br>At each dose level 6 healthy participants will receive a single dose of CK-0045 by s.c. administration | Drug: CK-0045<br>* Interleukin-22 agonist<br>|
| Placebo Comparator: SAD placebo<br>At each dose level 2 healthy participants will receive a single dose of matching placebo by s.c. administration | Drug: Placebo<br>* Matching placebo<br>|
| Experimental: Multiple ascending dose (MAD) CK-0045 Dose level 1 to 3<br>At each dose level 9 otherwise healthy participants with obesity will receive a loading dose of CK-0045 on Day 1 followed by a dose on Day 8, Day 15, Day 22, Day 29 and Day 36 of CK-0045 by s.c. administration | Drug: CK-0045<br>* Interleukin-22 agonist<br>|
| Placebo Comparator: MAD placebo<br>At each dose level 3 otherwise healthy participants with obesity will receive matching placebo on Day 1, Day 8 , Day 15, Day 22, Day 29 and Day 36 by s.c. administration | Drug: Placebo<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity and seriousness of treatment emergent adverse events | The safety and tolerability following single and multiple ascending doses of CK-0045 will be assessed | Up to 8 weeks after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) | The Cmax following single and multiple ascending doses of CK-0045 will be characterized | Day 1 to 8 weeks after last dose | 
| Area under the serum concentration-time curve from 0 to 168 hours (AUC168) after administration | AUC168 following single and multiple ascending doses of CK-0045 will be characterized | Day 1 to Day 8 | 
| Area under the serum concentration-time curve from 0 to infinity (AUCinf) | AUCinf following single and multiple ascending doses of CK-0045 will be characterized | Day 1 to 8 weeks after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interleukin-22, Safety, Tolerability, Pharmacokinetics