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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04993443

Registration number

NCT04993443

Ethics application status

Date submitted

17/05/2021

Date registered

6/08/2021

Date last updated

13/04/2023

Titles & IDs

Public title

First-In-Human Study to Evaluate the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of LQ036

Scientific title

A Single and Multiple-dose Escalation First-in-Human Study Evaluating the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of LQ036 Administered Via Inhalation and IV Infusion in Healthy Subjects and Patients With Mild Asthma.

Secondary ID [1]

LQ036A001

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Asthma

Condition category

Condition code

Respiratory

Asthma

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - LQ036
Other interventions - Matching Placebo

Experimental: Active Comparator: Drug :LQ036 - Experimental, Single and Multiple Oral escalating dose

Placebo comparator: Placebo Comparator: Matching Placebo for LQ036 - Matching Placebo for LQ036: Matching Placebo

Treatment: Drugs: LQ036
For Each part of the study, a staggered dosing schedule may be used for the first dose level, in each cohort including 2 sentinel subjects (1 active and 1 placebo) initiating dosing first and the remaining 6 subjects for Part A-C and 8 subjects for Part D initiating dosing no sooner than the next day. Each study part (A, B, C, and D) will be completed sequentially, but with partial overlapping. Part B and C may only be initiated after review of the safety, tolerability, and PK data following dosing of the SAD Cohort 3 or 4.

Part D may be initiated when safety tolerability and PK data are known and deemed acceptable by the SRC for multiple doses in Part B, at least at the same concentration to be administered in Part D.

Other interventions: Matching Placebo
Matching Placebo for LQ036: Matching Placebo

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Other interventions

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [1]

Up to 5 weeks.

Primary outcome [2]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [2]

Up to 1 Month

Primary outcome [3]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [3]

Up to 1 Month

Primary outcome [4]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [4]

Up to 1 Month

Primary outcome [5]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [5]

Up to 1 Month

Primary outcome [6]

To assess changes in cardiovascular system function (change in QTC parameters) as a criterion of safety and tolerability variables.

Timepoint [6]

Up to 1 Month

Primary outcome [7]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [7]

Up to 5 Weeks

Primary outcome [8]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [8]

Up to 5 Weeks

Primary outcome [9]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [9]

Up to 5 Weeks

Primary outcome [10]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [10]

Up to 5 Weeks

Primary outcome [11]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [11]

Up to 5 Weeks

Primary outcome [12]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [12]

Up to 5 Weeks

Primary outcome [13]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [13]

Up to 5 Weeks

Primary outcome [14]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [14]

Up to 5 Weeks

Primary outcome [15]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [15]

Up to 5 Weeks

Primary outcome [16]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [16]

Up to 5 Weeks

Primary outcome [17]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [17]

Up to 5 Weeks

Primary outcome [18]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [18]

Up to 5 Weeks

Primary outcome [19]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [19]

Up to 5 Weeks

Primary outcome [20]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [20]

Up to 5 Weeks

Primary outcome [21]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [21]

Up to 5 Weeks

Primary outcome [22]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [22]

Up to 5 Weeks

Primary outcome [23]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [23]

Up to 5 Weeks

Primary outcome [24]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [24]

Up to 5 Weeks

Primary outcome [25]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [25]

Up to 5 Weeks

Primary outcome [26]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [26]

Up to 5 Weeks

Primary outcome [27]

To evaluate the safety of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [27]

Up to 5 Weeks

Primary outcome [28]

To evaluate the tolerability of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [28]

Up to 5 weeks

Primary outcome [29]

To evaluate the immunogenicity of single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [29]

Up to 5 Weeks

Primary outcome [30]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects.

Timepoint [30]

Up to 2 Weeks

Primary outcome [31]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects.

Timepoint [31]

Up to 2 Weeks

Primary outcome [32]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects.

Timepoint [32]

Up to 2 Weeks

Primary outcome [33]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [33]

Up to 2 Weeks

Primary outcome [34]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [34]

Up to 2 Weeks

Primary outcome [35]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [35]

Up to 2 Weeks

Primary outcome [36]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [36]

Up to 2 Weeks

Primary outcome [37]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [37]

Up to 2 Weeks

Primary outcome [38]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [38]

Up to 2 Weeks

Primary outcome [39]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [39]

Up to 2 Weeks

Primary outcome [40]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [40]

Up to 2 Weeks

Primary outcome [41]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects

Timepoint [41]

Up to 2 Weeks

Primary outcome [42]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects (Kel)

Timepoint [42]

Up to 2 Weeks

Primary outcome [43]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma (Racc)

Timepoint [43]

Up to 2 Weeks

Primary outcome [44]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma. (PTF%)

Timepoint [44]

Up to 2 Weeks

Primary outcome [45]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects.

Timepoint [45]

Up to 2 Weeks

Primary outcome [46]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects

Timepoint [46]

Up to 2 Weeks

Primary outcome [47]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [47]

Up to 2 Weeks

Primary outcome [48]

To evaluate the pharmacokinetics (PK) of LQ036 after single and multiple doses of LQ036 administered via inhalation and IV routes in healthy subjects and patients with mild Asthma.

Timepoint [48]

Up to 2 Weeks

Primary outcome [49]

To evaluate the change in fraction exhaled nitric oxide (FeNO) after multiple doses of LQ036 administered via inhalation in patients with mild asthma.

Timepoint [49]

Up to 6 weeks

Secondary outcome [1]

To compare the PK of LQ036 after administration via inhalation and IV routes

Timepoint [1]

Up to 2 weeks

Secondary outcome [2]

To compare the safety and tolerability of LQ036 after administration via inhalation and IV routes (AUC0-24 versus AUC0-t)

Timepoint [2]

Up to 2 weeks

Secondary outcome [3]

To compare the safety and tolerability of LQ036 after administration via inhalation and IV routes (Cmax versus Cmax ss)

Timepoint [3]

Up to 2 weeks

Secondary outcome [4]

To compare the safety and tolerability of LQ036 after administration via inhalation and IV routes (Tmax versus Tmax ss)

Timepoint [4]

Up to 2 weeks

Secondary outcome [5]

To compare the PK of LQ036 after administration via inhalation in healthy subjects versus patients with mild asthma.

Timepoint [5]

Up to 2 weeks

Secondary outcome [6]

To compare the safety and tolerability of LQ036 via inhalation in healthy subjects versus patients with mild asthma. (AUC0-24 versus AUC0-t)

Timepoint [6]

Up to 2 weeks

Secondary outcome [7]

To compare the safety and tolerability of LQ036 via inhalation in healthy subjects versus patients with mild asthma. (Cmax versus Cmax ss)

Timepoint [7]

Up to 2 weeks

Secondary outcome [8]

To compare the safety and tolerability of LQ036 via inhalation in healthy subjects versus patients with mild asthma. (Tmax versus Tmax ss)

Timepoint [8]

Up to 2 weeks

Eligibility

Key inclusion criteria

* Healthy as defined by:

1. the absence of clinically significant illness and surgery within 4 weeks prior to dosing.
2. the absence of a clinically significant history of neurological, endocrine, cardiovascular, respiratory (except resolved childhood asthma), hematological, immunological, psychiatric (except including depression that has not required treatment for at least 6 months), gastrointestinal, renal, hepatic, and metabolic disease.
* Male or female, non-smokers or casual smokers (defined as smoking the equivalent of less than an average of 5 cigarettes per week over a 3 month period, and willing to abstain from smoking during involvement in the study and for 1 month prior to screening), =18 and =55 years of age, with BMI >18.0 and <32.0 kg/m2.
* Females of childbearing potential who are sexually active with a male partner must be willing to use one of the following acceptable contraceptive methods throughout the study and for 30 days after the last study drug administration:

1. Simultaneous use of intrauterine device placed at least 4 weeks prior to study drug administration, and condom for the male partner;
2. Simultaneous use of hormonal contraceptives started at least 4 weeks prior to study drug administration and condom for the male partner.
3. Sterile male partner (vasectomized since at least 6 months).
* Male subjects who are sexually active with a female partner of childbearing potential (childbearing potential females are defined as women that are neither post-menopausal nor surgically sterile) must be willing to use one of the following acceptable contraceptive methods from the first study drug administration until at least 90 days after the last study drug administration:

1. Simultaneous use of a male condom and, for the female partner, hormonal contraceptives used since at least 4 weeks, or intra-uterine contraceptive device placed since at least 4 weeks;
2. Male subjects must be willing not to donate sperm until 90 days following the last study drug administration.
* Subjects with normal lung function defined as greater than or equal to 80% predicted forced expiratory volume in one second (FEV1).
* Males and females who are in same-sex relationships can be included. There are no mandatory contraceptive requirements for males or females in same-sex relationships.
* Male and female heterosexual subjects who practice abstinence from sexual intercourse as a usual and preferred lifestyle.
* Part D only: Volunteers with mild asthma defined as:

1. Asthma diagnosed with appropriate medical documentation;
2. FEV1 =70% predicted FEV1 and FEV1/FVC ratio =0.7 at screening;
3. FeNO =35 ppb at screening;
4. Well-controlled, or partly-controlled, by as-needed use of short-acting ß2 agonists for at least 3 months prior to dosing;
5. Reversibility test at screening consistent with diagnosis of asthma (=12% and 200 mL increase in FEV1 over the baseline value).
* Capable of consent

Minimum age

18 Years

Maximum age

55 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

* Any clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results or positive test for HIV, hepatitis B, or hepatitis C found at screening or at check-in (Day -1, not applicable to serology assessments).
* Any clinically significant illness, infection, medical/surgical procedure, or trauma within 4 weeks of check-in, or planned inpatient surgery or hospitalization during the study period.
* Any history of malignancy or neoplastic disease (not including excised, non-recurrent, non-melanoma skin cancers).
* Positive urine drug screen, urine cotinine test, or alcohol breath test at screening or at check-in (Day -1).
* History of allergic reactions to LQ036, to any biologic therapy, or other related drugs, or to any excipient in the formulation.
* Positive pregnancy test at screening or at check-in (Day -1)
* Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood pressure less than 90 or greater than 140 mmHg, diastolic blood pressure less than 40 or greater than 90 mmHg, or heart rate less than 40 or greater than 100 bpm) at screening.
* History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit. Regular use of alcohol is defined as greater than 14 units of alcohol per week, where 1 unit is defined as 100 mL of wine at 13.5% a/v, 375 mL of beer at 3.5% a/v, or 30 mL of spirit at 40% a/v.
* History of significant drug abuse within 1 year prior to screening or use of soft drugs (such as tetrahydrocannabinol) within 1 month prior to the screening visit or hard drugs (amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine, and phencyclidine) within 3 months prior to screening.
* Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
* Use of medications for the timeframes specified below, with the exception of medications exempted by the Investigator on a case-by-case basis because they are judged unlikely to affect the PK profile of the study drug or subject safety (e.g., topical drug products without significant systemic absorption):

1. Prescription medications (except for hormonal contraceptives in all study parts and short-acting ß2 agonists for patients in Part D) within 14 days prior to the first dosing;
2. Over-the-counter products and natural health products (including herbal remedies, homeopathic and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports) within 7 days prior to the first dosing, with the exception of the occasional use of paracetamol/acetaminophen (up to 2 g daily), ibuprofen (up to 800 mg daily), and oral contraceptives;
3. Depot injection or implant (except for hormonal contraceptives) of any drug within 3 months prior to the first dosing;
4. Long-acting ß2 agonists for 4 weeks prior to screening;
5. Anti-immunoglobulin E,anti-Interleukin-5, or anti-Interleukin-4 Receptor therapy for 6 months prior to screening;
6. Inhaled corticosteroids (greater than 500 µg/day of beclometasone dipropionate or equivalent) within 16 weeks prior to screening,
7. Oral or injectable steroids for the treatment of asthma or respiratory tract infection within 5 years prior to screening;
8. Intranasal steroids within 4 weeks prior to screening;
9. Topical steroids within 4 weeks prior to screening;
10. Leukotriene antagonists within 2 weeks prior to screening;
11. Anticholinergics or cromoglycate within 1 week prior to screening.
12. Inhaled short-acting ß2 agonists (such as salbutamol) within 6 months prior to screening (not applicable to patients in Part D).
* Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.
* Breast-feeding subject.
* History of latent or active tuberculosis, or exposure to endemic areas within 8 weeks prior to QuantiFERON®-TB testing performed at screening.
* Positive QuantiFERON®-TB test indicating possible tuberculosis infection.
* Immunization with a live attenuated vaccine within 1 month prior to dosing or planned vaccination during the course of the study.
* Serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to screening.
* History of clinically significant opportunistic infection (e.g., invasive candidiasis or one pneumocystis pneumonia).
* History of parasitic diseases (e.g., toxoplasmosis, cysticercosis, toxocariasis).
* History of frequent, recurrent herpes simplex.
* Presence of fever (body temperature greater than 37.6 °C) e.g., a fever associated with a symptomatic viral or bacterial infection, within 2 weeks prior to the first dosing.
* Life threatening asthmatic episode at any time in the past.
* C-reactive protein level above 5 mg/L.
* Any reason that, in the opinion of the Investigator, would prevent the subject from participating in the study.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 1

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Stopped early

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

6/09/2021

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

9/03/2023

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD,VIC

Recruitment hospital [1]

Q-Pharm Pty Ltd (Nucleus Network Brisbane) - Brisbane

Recruitment hospital [2]

Nucleus Network Melbourne - Melbourne

Recruitment postcode(s) [1]

4006 - Brisbane

Recruitment postcode(s) [2]

3004 - Melbourne

Funding & Sponsors

Primary sponsor type

Other

Name

Syneos Health

Address

Country

Other collaborator category [1]

Other

Name [1]

Shanghai Novamab Biopharmaceuticals Co. Ltd.

Address [1]

Country [1]

Ethics approval

Ethics application status

Summary

Brief summary

This is Phase I first-in-human trial evaluating the safety, tolerability, immunogenicity, and pharmacogenomics of LQ036 via inhalation and IV infusion.

The study will be divided into 4 parts: Single Ascending Dose, Multiple Ascending Dose, and Intra Venous with a target of 88 healthy volunteers and 30 patients with mild Asthma.

Trial website

https://clinicaltrials.gov/study/NCT04993443

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Huaiyu Gu

Address

Shanghai Novamab Biopharm Co., Ltd.

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04993443

Trial Review

Registering a new trial?

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04993443