Trial Outcomes & Findings for To Assess the Safety and Activity of GBR 830, Compared to Placebo, in Adults With Moderate-to-severe Atopic Dermatitis (NCT NCT02683928)

Last Updated: 2020-05-18

Results Overview

A treatment-emergent adverse event (TEAE) was defined as any new adverse event (AEs) or worsening of an existing condition after administration of the study drug up to and including the follow-up visit.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

64 participants

Primary outcome timeframe

16 weeks

Results posted on

2020-05-18

Participant Flow

Participant milestones

Participant milestones
Measure	GBR 830 Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Overall Study STARTED	48	16
Overall Study COMPLETED	26	8
Overall Study NOT COMPLETED	22	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

To Assess the Safety and Activity of GBR 830, Compared to Placebo, in Adults With Moderate-to-severe Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GBR 830 n=46 Participants Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo n=16 Participants Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart	Total n=62 Participants Total of all reporting groups
Age, Continuous	36.2 years STANDARD_DEVIATION 13.38 • n=5 Participants	40.4 years STANDARD_DEVIATION 15.14 • n=7 Participants	37.3 years STANDARD_DEVIATION 13.85 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	5 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	11 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=5 Participants	16 Participants n=7 Participants	58 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	11 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
BMI	26.10 kg/m^2 STANDARD_DEVIATION 4.086 • n=5 Participants	26.23 kg/m^2 STANDARD_DEVIATION 3.688 • n=7 Participants	26.13 kg/m^2 STANDARD_DEVIATION 3.958 • n=5 Participants

PRIMARY outcome

Timeframe: 16 weeks

Population: The Safety Analysis Set consisted of all participants who took at least 1 full or partial dose of study treatment and were used in the assessment and reporting of safety data.

Outcome measures

Outcome measures
Measure	GBR 830 n=46 Participants Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo n=16 Participants Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Incidence of Treatment-Emergent Adverse Events experiencing at least 1 TEAE	29 Participants	10 Participants
Incidence of Treatment-Emergent Adverse Events experiencing at least 1 SAE	1 Participants	0 Participants
Incidence of Treatment-Emergent Adverse Events TEAE leading to permanent withdrawal of study drug	2 Participants	1 Participants
Incidence of Treatment-Emergent Adverse Events TEAE related to study drug	4 Participants	4 Participants

PRIMARY outcome

Timeframe: Day 1, before dosing (baseline), and Day 29 and Day 71, after dosing.

Population: The Biological Activity Set (BAS) consisted of all FAS subjects who had at least 1 post-baseline skin biopsy (Visit 7, Visit 13), and received 2 doses of study drug. The primary analyses on biomarkers of disease activity obtained from biopsy were based on the BAS. Subjects were analyzed according to the treatment to which they were randomized.

Epidermal thickness was assessed in Hematoxylin and Eosin stained sections of lesional skin biopsies on Day 1 (baseline), Day 29, and Day 71.

Outcome measures

Outcome measures
Measure	GBR 830 n=29 Participants Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo n=11 Participants Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Change From Baseline in Thickness of Lesional Skin Biopsies Baseline	140.56 micrometer Standard Deviation 57.623	124.95 micrometer Standard Deviation 47.021
Change From Baseline in Thickness of Lesional Skin Biopsies Change from Baseline in H&E Thickness to Day 29	-14.90 micrometer Standard Deviation 57.787	-3.02 micrometer Standard Deviation 51.589
Change From Baseline in Thickness of Lesional Skin Biopsies Change from Baseline in H&E Thickness to Day 71	-26.51 micrometer Standard Deviation 88.676	-6.01 micrometer Standard Deviation 39.402

PRIMARY outcome

Timeframe: 71 days

Population: The Biological Activity Set (BAS) consisted of all FAS participants who had at least 1 post-baseline skin biopsy (Visit 7, Visit 13), and received 2 doses of drug. The primary analyses on biomarkers of disease activity obtained from biopsy were based on the BAS. Participants were analyzed according to the treatment to which they were randomized.

Ratio of post-baseline/baseline value of messenger ribonucleic acid (mRNA) expression in lesional skin biopsies is reported.

Outcome measures

Outcome measures
Measure	GBR 830 n=29 Participants Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo n=11 Participants Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies CCL11/hARP	0.67 ratio Interval 0.4 to 1.13	1.20 ratio Interval 0.5 to 2.9
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies CCL17/hARP	0.62 ratio Interval 0.38 to 1.01	0.75 ratio Interval 0.34 to 1.67
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies CCL18/hARP	0.75 ratio Interval 0.59 to 0.96	0.64 ratio Interval 0.43 to 0.96
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies CCL26/hARP	0.81 ratio Interval 0.63 to 1.03	0.67 ratio Interval 0.45 to 1.01
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies CXCL10/hARP	0.53 ratio Interval 0.36 to 0.79	0.85 ratio Interval 0.45 to 1.63
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies FOXP3/hARP	0.88 ratio Interval 0.77 to 1.02	0.93 ratio Interval 0.74 to 1.16
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies INFg/hARP	0.77 ratio Interval 0.48 to 1.23	1.34 ratio Interval 0.62 to 2.91
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies IL-23p40/hARP	0.74 ratio Interval 0.52 to 1.04	0.71 ratio Interval 0.41 to 1.23
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies IL-5/hARP	0.72 ratio Interval 0.39 to 1.32	0.67 ratio Interval 0.25 to 1.84
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies IL13/hARP	0.96 ratio Interval 0.52 to 1.76	0.43 ratio Interval 0.16 to 1.11
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies IL17A/hARP	1.01 ratio Interval 0.55 to 1.87	0.70 ratio Interval 0.25 to 1.96
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies IL22/hARP	0.64 ratio Interval 0.42 to 0.99	0.47 ratio Interval 0.23 to 0.97
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies IL23p19/hARP	0.92 ratio Interval 0.82 to 1.03	0.97 ratio Interval 0.81 to 1.17
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies K16/hARP	0.58 ratio Interval 0.39 to 0.86	0.72 ratio Interval 0.37 to 1.38
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies MMP12/hARP	0.58 ratio Interval 0.36 to 0.92	0.40 ratio Interval 0.19 to 0.85
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies OX40L/hARP	1.04 ratio Interval 0.88 to 1.22	1.24 ratio Interval 0.97 to 1.58
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies S100A12/hARP	0.42 ratio Interval 0.25 to 0.72	0.58 ratio Interval 0.24 to 1.39
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies S100A9/hARP	0.51 ratio Interval 0.33 to 0.78	0.63 ratio Interval 0.31 to 1.28
Change From Baseline in Ratio of Active Atopic Dermatitis Messenger Ribonucleic Acid (mRNA) Expression (Normalized to Human Acidic Ribosomal Protein [hARP]) in Lesional Skin Biopsies TSLRP/hARP	0.91 ratio Interval 0.79 to 1.05	0.84 ratio Interval 0.67 to 1.06

SECONDARY outcome

Timeframe: Day 4, Day 29, Day 57, Day 71

Population: Full Analysis Set (FAS): The FAS consisted of all participants who were randomized and received at least 1 partial or full dose of study treatment. The FAS population was used for the analysis of the efficacy data not obtained from skin biopsy. Participants were analyzed according to the treatment by which they were randomized.

In EASI, four disease characteristics of atopic dermatitis (erythema, edema/papulation, excoriation, and lichenification) are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the four body regions (Head and neck, trunk, arms, and legs). The assigned percentages of body surface area (BSA) for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs, respectively. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin in that area: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD.

Outcome measures

Outcome measures
Measure	GBR 830 n=46 Participants Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo n=16 Participants Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Percent Change in Eczema Area and Severity Index (EASI) Clinical Scores From Baseline Percent Change from Baseline to Visit 3 (Day 4)	-9.80 percentage of change from baseline Standard Deviation 14.253	-11.33 percentage of change from baseline Standard Deviation 16.835
Percent Change in Eczema Area and Severity Index (EASI) Clinical Scores From Baseline Percent Change from Baseline to Visit 7 (day 29)	-38.72 percentage of change from baseline Standard Deviation 36.148	-32.40 percentage of change from baseline Standard Deviation 31.918
Percent Change in Eczema Area and Severity Index (EASI) Clinical Scores From Baseline Percent Change from Baseline to Visit 12 (day 57)	-61.00 percentage of change from baseline Standard Deviation 31.951	-39.54 percentage of change from baseline Standard Deviation 46.791
Percent Change in Eczema Area and Severity Index (EASI) Clinical Scores From Baseline Percent Change from Baseline to Visit 13 (day 71)	-67.35 percentage of change from baseline Standard Deviation 23.107	-38.22 percentage of change from baseline Standard Deviation 37.865

SECONDARY outcome

Timeframe: Day 4, Day 29, Day 57, Day 71

Population: N is the number of participants in the respective treatment group. Numbers and percentages calculated at each visit are based on the number of participants achieving IGA score of 0 or 1 among those evaluable participants at each visit.

The IGA is an assessment scale used in clinical studies to determine severity of AD based on a 5-point scale ranging from 0 (clear) to 4 (severe/very severe).

Outcome measures

Outcome measures
Measure	GBR 830 n=46 Participants Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo n=16 Participants Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 Visit 3 (day 4)	0 Participants	0 Participants
Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 Visit 7 (day 29)	2 Participants	0 Participants
Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 Visit 12 (day 57)	6 Participants	2 Participants
Percentage of Participants Who Achieved an Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 Visit 13 (day 71)	6 Participants	1 Participants

SECONDARY outcome

Timeframe: Blood samples were collected on Day 1 and Day 29: pre-dose (15 mins), end of infusion (1 hour) and 1.5, 2, 72, and 504 hours post start of infusion

Population: The Pharmacokinetic Analysis Set (PKAS) consisted of the subset of the Safety Analysis Set population for which sufficient serum concentration data were available to facilitate derivation of at least 1 PK parameter, and the time (HH:MM) of dosing on the day of sampling was known for at least 1 of the dosing visits.

Pharmacokinetics in terms of Cmax (maximum observed concentration after second \[last\] dosing interval) was estimated after the first and second dose.

Outcome measures

Outcome measures
Measure	GBR 830 n=45 Participants Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Pharmacokinetics of GBR 830 in Terms of Cmax After First and Second Dose. Cmax after Second Dose	352 microgram/mL Geometric Coefficient of Variation 29	—
Pharmacokinetics of GBR 830 in Terms of Cmax After First and Second Dose. Cmax after First Dose	303 microgram/mL Geometric Coefficient of Variation 29	—

SECONDARY outcome

Timeframe: Blood samples were collected on Day 1 and Day 29: pre-dose (15 mins), end of infusion (1 hour) and 1.5, 2, 72, and 504 hours post start of infusion

Pharmacokinetics in terms of AUC0-tau \[Trapezoid calculation of area under the serum drug concentration-time curve from time zero (pre dose time point of the infusion) to the end of the dosing interval\] was estimated.

Outcome measures

Outcome measures
Measure	GBR 830 n=40 Participants Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Pharmacokinetics of GBR 830 in Terms of AUC0-tau After the First and Second Dose. AUC0-tau after the First Dose	57217 microgram*hour/mL Geometric Coefficient of Variation 26	—
Pharmacokinetics of GBR 830 in Terms of AUC0-tau After the First and Second Dose. AUC0-tau after the Second Dose	69670 microgram*hour/mL Geometric Coefficient of Variation 29	—

SECONDARY outcome

Timeframe: Samples collected for immunogenicity analysis at Baseline (pre-dose), and at Day 15, Day 29 (pre-dose), Day 57, and Day 85.

Population: The Safety Analysis Set consisted of all particpants who took at least 1 full or partial dose of study treatment and were used in the assessment and reporting of safety data.

Blood samples were collected at time points to detect anti-drug antibodies (ADAs) to GBR 830, as per procedures similar to collection of PK samples. Antibodies of GBR 830 were detected and confirmed using a validated enzyme-linked immunosorbent assay (ELISA) method.

Outcome measures

Outcome measures
Measure	GBR 830 n=46 Participants Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo n=16 Participants Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Number of Participants Positive or Negative for Anti-drug Antibodies (ADA) to GBR 830 to Evaluate Immunogenicity Positive	6 Participants	1 Participants
Number of Participants Positive or Negative for Anti-drug Antibodies (ADA) to GBR 830 to Evaluate Immunogenicity Negative	40 Participants	15 Participants

Adverse Events

GBR 830

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GBR 830 n=46 participants at risk Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo n=16 participants at risk Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Cardiac disorders Coronary artery occlusion	2.2% 1/46 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	0.00% 0/16 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.

Other adverse events

Additional Information

Study Director

Ichnos Sciences SA

Phone: 2013314000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	GBR 830 n=46 participants at risk Two doses of GBR 830, 10 mg/kg (solution for infusion, prepared in normal saline) administered intravenously (IV) four weeks apart	Placebo n=16 participants at risk Two doses of placebo (formulation buffer for infusion, prepared in normal saline) administered IV four weeks apart
Infections and infestations Nasopharyngitis	8.7% 4/46 • Number of events 5 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	12.5% 2/16 • Number of events 2 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Infections and infestations Upper respiratory tract infection	8.7% 4/46 • Number of events 5 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	12.5% 2/16 • Number of events 2 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Infections and infestations post procedural infection	8.7% 4/46 • Number of events 4 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	0.00% 0/16 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Infections and infestations Gastroenteritis	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	12.5% 2/16 • Number of events 2 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Infections and infestations Tooth abscess	2.2% 1/46 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Infections and infestations Lice infestation	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Skin and subcutaneous tissue disorders Dermatitis atopic	13.0% 6/46 • Number of events 6 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	12.5% 2/16 • Number of events 2 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	12.5% 2/16 • Number of events 2 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Nervous system disorders Headache	13.0% 6/46 • Number of events 7 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	25.0% 4/16 • Number of events 5 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Nervous system disorders Syncope	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Musculoskeletal and connective tissue disorders Myalgia	6.5% 3/46 • Number of events 3 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	0.00% 0/16 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Gastrointestinal disorders Toothache	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 3 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
General disorders Fatigue	4.3% 2/46 • Number of events 4 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Cardiac disorders Supraventricular tachycardia	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Injury, poisoning and procedural complications Laceration	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Psychiatric disorders Insomnia	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	12.5% 2/16 • Number of events 2 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/46 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.	6.2% 1/16 • Number of events 1 • AEs and SAEs were collected from the time of signing the informed consent form (ICF) until the follow up for a total duration of 16 weeks. A total of 64 eligible participants were randomized to receive either GBR 830 or corresponding placebo. Two participants assigned to GBR 830 withdrew informed consent before dosing. Therefore, a total of 62 subjects were included in the Full Analysis Set and Safety Analysis Set.