Study of Intravenously Administered Anti-LIGHT Monoclonal Antibody CBS001 in Healthy Volunteers

A Double-blind, Randomized, Placebo-controlled, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Immunogenicity of Single- and Multiple-ascending Doses of Intravenously Administered Anti-LIGHT Monoclonal Antibody CBS001 in Healthy Volunteers

A Phase 1, first in human (FIH), single-centre, double-blind, randomized, placebo-controlled, dose escalating trial to assess the safety and tolerability, pharmacokinetics (PK), immunogenicity and pharmacodynamics (PD) of CBS001 in healthy subjects. The study will be conducted in 2 parts:

Part A: Single ascending intravenous (IV) doses of CBS001 Part B: Multiple ascending IV doses of CBS001

Study Overview

• Status: Terminated
• Conditions: Chronic Inflammatory Disease
• Intervention / Treatment: Drug: CBS001; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7EW
    • HMR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female healthy volunteer.
2. Aged 18-65 years.
3. A body mass index (BMI; Quetelet index) in the range 18.0-30.9. Body Mass Index = weight (kg)/(height[m]^2
4. Ability to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
5. Willingness to give written consent to participate after reading the information and consent form (ICF), and after having the opportunity to discuss the trial with the investigator or their delegate.
6. Agree to follow the contraception requirements of the trial
7. Agree not to donate blood or blood products during the study and for up to 3 months after the administration of the trial medication or until the final follow-up visit (whichever is longer).
8. Registered with a General Practitioner (GP) in the United Kingdom.
9. Willingness to give written consent to have data entered into The Overvolunteering Prevention System (TOPS).

Exclusion Criteria:

1. Woman who is pregnant or lactating, or pre-menopausal woman who is sexually active and not using a reliable method of contraception.
2. Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
3. Isolated bilirubin > 1.5 x upper limit of normal (ULN). Isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is < 35% indicative of Gilbert's syndrome.
4. Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous.
5. Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, allergic diseases such as asthma or atopic dermatitis requiring medication, or history of any psychotic mental illness.
6. Presence or history of severe adverse reaction to any drug or a history of sensitivity to any CBS001 excipient.
7. Use of a prescription medicine (except hormone contraceptives or hormone replacement therapy [HRT] in women) during the 28 days before the (first) dose of trial medication, or use of an over-the-counter medicine (except acetaminophen [paracetamol], dietary supplement, or herbal remedy) including St John's Wort during the 7 days before the (first) dose of trial medication.
8. Receipt of an investigational product (including prescription medicines) as part of another clinical trial within the 3 months before [first] admission to this study; in the follow-up period of another clinical trial at the time of screening for this study.
9. Receipt of an approved or investigational biological product within the 12 months before screening.
10. Receipt of a vaccination (except COVID-19 vaccine) within 28 days before (first) dose of trial medication, or planned vaccination during the study.
11. Presence or history of drug or alcohol abuse, or intake of more than 14 units of alcohol weekly, or more than 10 cigarettes or 6.25 g of tobacco daily.
12. Blood pressure and heart rate in supine position at the screening examination outside the ranges: blood pressure 90-140 mm Hg systolic, 40-90 mm Hg diastolic; heart rate 40-100 beats/min. Repeat measurements are permitted if values are borderline (ie values that are within 5 mm Hg for blood pressure or 5 beats/min for heart rate) or if requested
13. Corrected QT interval (QTcF) value greater than 450 msec (men) or greater than 470 msec (women) measured on 12-lead ECG at the screening examination. Triplicate measurements will be made, and a mean value used to determine eligibility. A repeat (in triplicate) is also allowed on 1 occasion for determination of eligibility. Participants can be included if the repeat value is within range or still borderline, but deemed not clinically significant by the investigator.
14. Possibility that the volunteer will not cooperate with the requirements of the protocol.
15. Evidence of drug abuse on urine testing.
16. Positive test for hepatitis B, hepatitis C (unless has received curative antiviral treatment and has a negative polymerase chain reaction [PCR] for viral load) or HIV. Loss of more than 400 mL blood during the 3 months before the study, eg as a blood donor.
17. Objection by GP to volunteer entering study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A - Cohort 1A; Single dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo
Experimental: Part A - Cohort 2A; Single dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo
Experimental: Part A - Cohort 3A; Single dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo
Experimental: Part A - Cohort 4A; Single dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo
Experimental: Part A - Cohort 5A; Single dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo
Experimental: Part A - Cohort 6A; Single dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo
Experimental: Part A - Cohort 7A; Single dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo
Experimental: Part A - Cohort 8A; Single dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo
Experimental: Part B - Cohort 1B; Multiple dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo
Experimental: Part B - Cohort 2B; Multiple dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo
Experimental: Part A - Cohort 3B; Multiple dose cohort	Drug: CBS001; Intravenously administered, humanised anti-LIGHT IgG monoclonal antibody.; Drug: Placebo; CBS001 matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Part A)	Number of Participants with One or More Drug Related Adverse Events (AEs) or any Serious AEs	Up to Day 190
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Part B)	Number of Participants with One or More Drug Related Adverse Events (AEs) or any Serious AEs	Up to Day 247

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CBS001 plasma evaluation over time (Part A)	CBS001 plasma concentrations will be measured at specified visits	Up to Day 190
CBS001 plasma evaluation over time (Part B)	CBS001 plasma concentrations will be measured at specified visits	Up to Day 247
Antibodies against CBS001 in serum (Part A)	Immunogenicity	Up to Day 190
Antibodies against CBS001 in serum (Part B)	Immunogenicity	Up to Day 247

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentrations of pharmacodynamic marker(s) (Part A) (Exploratory)	Serum concentrations of pharmacodynamic marker(s) will be measured at specified visits	Up to Day 190
Serum concentrations of pharmacodynamic marker(s) (Part B) (Exploratory)	Serum concentrations of pharmacodynamic marker(s) will be measured at specified visits	Up to Day 247

Collaborators and Investigators

• Sponsor: Capella Bioscience Ltd
• Collaborators: Centessa Pharmaceuticals plc

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2022
• Primary Completion (Actual): August 22, 2023
• Study Completion (Actual): August 22, 2023

Study Registration Dates

• First Submitted: April 5, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: CBS001-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No