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Clinical Trial Results:
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study to Evaluate the Efficacy and Safety of Oral SKI-O-703 in Patients With Active Rheumatoid Arthritis Despite Treatment With Conventional Therapies

Summary
EudraCT number	2018-003330-32
Trial protocol	PL
Global end of trial date	13 Oct 2020

Results information
Results version number	v1(current)
This version publication date	20 Jun 2021
First version publication date	20 Jun 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

OSCO-P2201

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Oscotec Inc.

Sponsor organisation address

Korea Bio-Park, Building A, 9th Floor, 700 Daewangpangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea, Republic of, 13488

Public contact

Clinical Trials Information, Oscotec Inc., +82 0316287661, clinical-oct@oscotec.com

Scientific contact

Clinical Trials Information, Oscotec Inc., +82 0316287661, clinical-oct@oscotec.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

23 Feb 2021

Is this the analysis of the primary completion data?

Yes

Primary completion date

13 Oct 2020

Global end of trial reached?

Yes

Global end of trial date

13 Oct 2020

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy of select (100 mg twice daily [BID], 200 mg BID, and 400 mg BID) doses of SKI-O-703 compared with placebo in subjects with active RA who have had an inadequate response to csDMARDs or previous 1, 2, or more anti-TNFα biologic agents

Protection of trial subjects

The study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki, ICH GCP, and all applicable regulations. A written informed consent in compliance with the respective applicable regulatory authority regulations was obtained from each subject before entering the study or performing any unusual or nonroutine procedure that involved risk to the subject. Before recruitment and enrollment, each prospective subject or his or her legal guardian was given a full explanation of the study and allowed to read the approved ICF. Once the investigator was assured that the subject/legal guardian understood the implications of participating in the study, the subject/legal guardian was asked to give consent to participate in the study by signing the ICF. The investigator retained the signed original ICF(s) and gave a copy of the signed original form to the subject or legal guardian.

Background therapy

Subjects were allowed to receive background permitted concomitant medications for RA, including MTX, and other oral DMARDs, in line with current standard of care practices for RA.

Evidence for comparator

There is no comparator.

Actual start date of recruitment

27 Mar 2019

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

1 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Korea, Republic of: 2

Country: Number of subjects enrolled

Poland: 25

Country: Number of subjects enrolled

Czechia: 3

Country: Number of subjects enrolled

Russian Federation: 22

Country: Number of subjects enrolled

Serbia: 16

Country: Number of subjects enrolled

Ukraine: 46

Country: Number of subjects enrolled

United States: 49

Worldwide total number of subjects

163

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

128

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Potential subjects were assessed as per the eligibility criteria. After completing all screening assessments, subjects who met all the inclusion and none of the exclusion criteria were enrolled into the study and were randomly assigned in 1:1:1:1 ratio to receive 1 of the 3 doses of SKI-O-703 (100 mg, 200 mg, or 400 mg) or placebo for 12 weeks.

Screening details

The study included a screening period of up to 28 days.

Period 1 title

12-Week Treatment period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Blinding implementation details

This was a double-blind study. Neither the subjects nor the investigator/site personnel were aware of the treatment assignment for the subjects in each cohort. Subject-specific doses were prepared and checked by blinded pharmacy staff and administered by appropriately trained blinded clinic staff as delegated by the Principal Investigator at the study site. Blinding was maintained throughout the study by use of active or placebo dosage forms of similar appearance.

Are arms mutually exclusive

Yes

SKI-O-703 100 mg

Arm description

Through the the double-blind 12-week treatment period, participants were randomly assigned to SKI-O-703 100 mg.

Arm type

Experimental

Investigational medicinal product name

SKI-O-703 100 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

One SKI-O-703 100 mg capsule and three placebo 100 mg capsules were administered BID, orally, no later than 30 minutes after food.

SKI-O-703 200 mg

Arm description

Through the the double-blind 12-week treatment period, participants were randomly assigned to SKI-O-703 200 mg.

Arm type

Experimental

Investigational medicinal product name

SKI-O-703 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Two SKI-O-703 100 mg capsules and two placebo 100g capsules were administered BID, orally, no later than 30 minutes after food.

SKI-O-703 400 mg

Arm description

Through the the double-blind 12-week treatment period, participants were randomly assigned to SKI-O-703 400 mg.

Arm type

Experimental

Investigational medicinal product name

SKI-O-703 400 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Four SKI-O-703 100 mg capsules were administered BID, orally, no later than 30 minutes after food.

Placebo

Arm description

Through the the double-blind 12-week treatment period, participants were randomly assigned to Placebo.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Four placebo capsules were administered BID, orally, no later than 30 minutes after food. Placebo capsules were identical in appearance and weight to the SKI-O-703 capsules and contained microcrystalline cellulose and magnesium stearate.

Number of subjects in period 1	SKI-O-703 100 mg	SKI-O-703 200 mg	SKI-O-703 400 mg	Placebo
Started	41	40	41	41
Completed	39	37	36	38
Not completed	2	3	5	3
Consent withdrawn by subject	2	-	2	2
Physician decision	-	1	1	-
Adverse event, non-fatal	-	1	1	1
Other	-	1	1	-

Baseline characteristics

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Reporting group title

SKI-O-703 100 mg

Reporting group description

Through the the double-blind 12-week treatment period, participants were randomly assigned to SKI-O-703 100 mg.

Reporting group title

SKI-O-703 200 mg

Reporting group description

Through the the double-blind 12-week treatment period, participants were randomly assigned to SKI-O-703 200 mg.

Reporting group title

SKI-O-703 400 mg

Reporting group description

Through the the double-blind 12-week treatment period, participants were randomly assigned to SKI-O-703 400 mg.

Reporting group title

Placebo

Reporting group description

Through the the double-blind 12-week treatment period, participants were randomly assigned to Placebo.

Reporting group values	SKI-O-703 100 mg	SKI-O-703 200 mg	SKI-O-703 400 mg	Placebo	Total
Number of subjects	41	40	41	41	163
Age categorical
Units: Subjects
Adults (18-64 years)	31	31	36	30	128
From 65-84 years	10	9	5	11	35
Age continuous
Units: years
median (full range (min-max))	57 (24 to 77)	58 (29 to 72)	52 (26 to 82)	55 (32 to 81)	-
Gender categorical
Units: Subjects
Female	29	32	33	34	128
Male	12	8	8	7	35

Subject analysis set title

Intention-to-treat set

Subject analysis set type

Intention-to-treat

Subject analysis set description

The ITT set was defined as all randomized subjects who received at least one dose of study drug (SKI-O-703 or placebo). Subjects were analyzed as randomized. This population was used for all efficacy analyses and summaries of demographics and baseline characteristics data.

Subject analysis set title

Modified ITT set

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

The modified ITT (mITT) set was defined as all the subjects who received at least one dose of study drug (SKI-O-703 or placebo) and had at least 1 postbaseline assessment. Subjects were analyzed as randomized.

Subject analysis set title

Per-protocol set

Subject analysis set type

Per protocol

Subject analysis set description

The Per-protocol (PP) set was defined as all the subjects in ITT set who did not have any major protocol deviation(s) which were flagged in the protocol deviation list and were compliant with the treatment. All the efficacy analyses were repeated on PP set. Subjects were analyzed as randomized.

Subject analysis set title

Safety set

Subject analysis set type

Safety analysis

Subject analysis set description

The safety set was defined as all subjects who received at least one dose of study drug (SKI-O-703 or placebo). Subjects were analyzed as treated. This population was used for summaries of safety data.

Subject analysis sets values	Intention-to-treat set	Modified ITT set	Per-protocol set	Safety set
Number of subjects	163	160	148	163
Age categorical
Units: Subjects
Adults (18-64 years)	128			128
From 65-84 years	35			35
Age continuous
Units: years
median (full range (min-max))	56 (24 to 82)			56 (24 to 82)
Gender categorical
Units: Subjects
Female	128			128
Male	35			35

End points

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Reporting group title

SKI-O-703 100 mg

Reporting group description

Through the the double-blind 12-week treatment period, participants were randomly assigned to SKI-O-703 100 mg.

Reporting group title

SKI-O-703 200 mg

Reporting group description

Through the the double-blind 12-week treatment period, participants were randomly assigned to SKI-O-703 200 mg.

Reporting group title

SKI-O-703 400 mg

Reporting group description

Through the the double-blind 12-week treatment period, participants were randomly assigned to SKI-O-703 400 mg.

Reporting group title

Placebo

Reporting group description

Through the the double-blind 12-week treatment period, participants were randomly assigned to Placebo.

Subject analysis set title

Intention-to-treat set

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Modified ITT set

Subject analysis set type

Modified intention-to-treat

Subject analysis set description

Subject analysis set title

Per-protocol set

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Safety set

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: Analysis of Change from Baseline in DAS28-hsCRP at Week 12

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End point title

Analysis of Change from Baseline in DAS28-hsCRP at Week 12

End point description

The primary efficacy endpoint was the mean change from baseline in DAS28-hsCRP at Week 12 based on 3 individual components including TJC28, SJC28, and hsCRP. DAS28-hsCRP was calculated only when all 3 individual components (TJC28, SJC28, and hsCRP) were assessed at this visit; otherwise, DAS28-hsCRP at Week 12 was considered as missing. The differences in DAS28-hsCRP LS Means were not statistically significant between any of the SKI-O-703 treatment groups and the placebo group.

End point type

Primary

End point timeframe

At week 12

End point values	SKI-O-703 100 mg	SKI-O-703 200 mg	SKI-O-703 400 mg	Placebo
Number of subjects analysed	41	40	41	41
Units: percent
arithmetic mean (standard deviation)
Baseline	5.52 ( 0.627 )	5.31 ( 0.819 )	5.38 ( 0.833 )	5.47 ( 0.874 )
Actual Value at Week 12	4.56 ( 1.006 )	4.30 ( 0.940 )	4.25 ( 1.191 )	4.50 ( 0.847 )
Change from Baseline at Week 12	-0.96 ( 0.892 )	-1.01 ( 1.030 )	-1.13 ( 1.074 )	-0.98 ( 0.892 )

Statistical Analysis Plan - 100 mg vs Placebo

Statistical analysis description

The change from baseline in DAS28-hsCRP at Week 12 was analyzed using an ANCOVA model. The model included treatment groups as a factor and DAS28-hsCRP at baseline as a covariate.

Comparison groups

Placebo v SKI-O-703 100 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.846

Method

ANCOVA

Parameter type

Difference in LS Mean

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

0.47

Variability estimate

Standard error of the mean

Dispersion value

0.217

Statistical Analysis Plan - 200 mg vs Placebo

Statistical analysis description

The change from baseline in DAS28-hsCRP at Week 12 was analyzed using an ANCOVA model. The model included treatment groups as a factor and DAS28-hsCRP at baseline as a covariate.

Comparison groups

Placebo v SKI-O-703 200 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.616

Method

ANCOVA

Parameter type

Difference in LS Mean

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

0.32

Variability estimate

Standard error of the mean

Dispersion value

0.218

Statistical Analysis Plan - 400 mg vs Placebo

Statistical analysis description

The change from baseline in DAS28-hsCRP at Week 12 was analyzed using an ANCOVA model. The model included treatment groups as a factor and DAS28-hsCRP at baseline as a covariate.

Comparison groups

Placebo v SKI-O-703 400 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.368

Method

ANCOVA

Parameter type

Difference in LS Mean

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.63

upper limit

0.23

Variability estimate

Standard error of the mean

Dispersion value

0.217

Adverse events

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Timeframe for reporting adverse events

Treatment emergent adverse events (TEAEs) have been measured during the 12 week Treatment Period.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

SKI-O-703 100 mg

Reporting group description

SKI-O-703 capsules were provided as Swedish orange capsules and contained the active ingredient SKI-O-703 (100 mg). SKI-O-703 100 mg was administered BID, orally, no later than 30 minutes after food.

Reporting group title

SKI-O-703 200 mg

Reporting group description

SKI-O-703 capsules were provided as Swedish orange capsules and contained the active ingredient SKIO-703 (100 mg). SKI-O-703 200 mg was administered BID, orally, no later than 30 minutes after food.

Reporting group title

SKI-O-703 400 mg

Reporting group description

SKI-O-703 capsules were provided as Swedish orange capsules and contained the active ingredient SKIO-703 (100 mg). SKI-O-703 400 mg was administered BID, orally, no later than 30 minutes after food.

Reporting group title

Placebo

Reporting group description

Placebo capsules were identical in appearance and weight to the SKI-O-703 capsules and contained microcrystalline cellulose and magnesium stearate. Placebo was administered BID, orally, no later than 30 minutes after food.

Serious adverse events	SKI-O-703 100 mg	SKI-O-703 200 mg	SKI-O-703 400 mg	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	1 / 41 (2.44%)	1 / 41 (2.44%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial adenocarcinoma
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Myocarditis
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia viral
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	SKI-O-703 100 mg	SKI-O-703 200 mg	SKI-O-703 400 mg	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	16 / 41 (39.02%)	23 / 40 (57.50%)	25 / 41 (60.98%)	19 / 41 (46.34%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial adenocarcinoma
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Vascular disorders
Flushing
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Pyrexia
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Allergy to plants
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Reproductive system and breast disorders
Endometrial hyperplasia
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Metrorrhagia
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Emphysema
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	2 / 41 (4.88%)	0 / 40 (0.00%)	4 / 41 (9.76%)	0 / 41 (0.00%)
occurrences all number	2	0	4	0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	3 / 41 (7.32%)	0 / 41 (0.00%)
occurrences all number	1	0	3	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	2 / 41 (4.88%)	1 / 41 (2.44%)
occurrences all number	0	0	2	1
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	2 / 41 (4.88%)	0 / 41 (0.00%)
occurrences all number	0	0	2	0
Blood pressure increased
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	1	1	0
Neutrophil count decreased
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Weight decreased
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Blood bilirubin increased
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Blood potassium decreased
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Platelet count increased
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Weight increased
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Cardiac disorders
Left ventricular hypertrophy
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Sinus tachycardia
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Ventricular extrasystoles
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Myocarditis
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Nervous system disorders
Headache
subjects affected / exposed	1 / 41 (2.44%)	6 / 40 (15.00%)	6 / 41 (14.63%)	2 / 41 (4.88%)
occurrences all number	1	6	6	2
Somnolence
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	1	0	1
Sciatica
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Blood and lymphatic system disorders
Iron deficiency anaemia
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	2 / 41 (4.88%)	0 / 41 (0.00%)
occurrences all number	0	0	2	0
Neutropenia
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	1 / 41 (2.44%)	1 / 41 (2.44%)
occurrences all number	0	1	1	1
Hypochromic anaemia
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Microcytic anaemia
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Eye disorders
Chalazion
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Vertigo
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	1	0	0	1
Gastrointestinal disorders
Nausea
subjects affected / exposed	0 / 41 (0.00%)	3 / 40 (7.50%)	2 / 41 (4.88%)	2 / 41 (4.88%)
occurrences all number	0	3	2	2
Constipation
subjects affected / exposed	3 / 41 (7.32%)	0 / 40 (0.00%)	1 / 41 (2.44%)	4 / 41 (9.76%)
occurrences all number	3	0	1	4
Dyspepsia
subjects affected / exposed	0 / 41 (0.00%)	3 / 40 (7.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	3	0	0
Diarrhoea
subjects affected / exposed	2 / 41 (4.88%)	1 / 40 (2.50%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	2	1	1	0
Flatulence
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Haematochezia
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Epigastric discomfort
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Toothache
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Periodontal disease
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Hepatobiliary disorders
Hepatic steatosis
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Hepatic function abnormal
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Rosacea
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Urticaria
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Urethral syndrome
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Leukocyturia
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	2 / 41 (4.88%)	0 / 41 (0.00%)
occurrences all number	0	0	2	0
Rheumatoid arthritis
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Arthralgia
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Joint range of motion decreased
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Pain in extremity
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Synovitis
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	0	1	0
Bursitis
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Infections and infestations
Rhinitis
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	2 / 41 (4.88%)	0 / 41 (0.00%)
occurrences all number	0	1	2	0
Bronchitis
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	2 / 41 (4.88%)
occurrences all number	0	0	0	2
Asymptomatic bacteriuria
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	1	1	0
Nasopharyngitis
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	1	1	0
Urinary tract infection
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	1 / 41 (2.44%)	1 / 41 (2.44%)
occurrences all number	0	0	1	1
Upper respiratory tract infection
subjects affected / exposed	0 / 41 (0.00%)	2 / 40 (5.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	2	0	0
Cystitis
subjects affected / exposed	1 / 41 (2.44%)	1 / 40 (2.50%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	1	1	0	1
Respiratory tract infection viral
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	1	0	1
Oral herpes
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Gastroenteritis viral
subjects affected / exposed	1 / 41 (2.44%)	0 / 40 (0.00%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	1	0	0	0
Genital infection
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Pneumonia viral
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Respiratory tract infection
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Metabolism and nutrition disorders
Hyperkalaemia
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	1 / 41 (2.44%)	0 / 41 (0.00%)
occurrences all number	0	1	1	0
Vitamin D deficiency
subjects affected / exposed	0 / 41 (0.00%)	1 / 40 (2.50%)	0 / 41 (0.00%)	0 / 41 (0.00%)
occurrences all number	0	1	0	0
Hypercholesterolaemia
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1
Type 2 diabetes mellitus
subjects affected / exposed	0 / 41 (0.00%)	0 / 40 (0.00%)	0 / 41 (0.00%)	1 / 41 (2.44%)
occurrences all number	0	0	0	1

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Were there any global substantial amendments to the protocol? Yes

05 Dec 2018

• The word “patient” was replaced with “subject” throughout the protocol. • Added EudraCT number on protocol title page. • Added food effect rationale from recently completed food effect study following single oral administration of 400 mg SKI-O-703 (Study OSCO-P1203). • Added justification for use of placebo in the study as per the request from regulatory group. • Provided detailed information of procedures and assessments to be done during each period (at screening and randomization [Day 1], 12-week treatment period, and 4-week follow-up period). Also added details of subject error. Details of randomization visit (Study Day 1) has been updated and provided clarification for PK/PD subsets. • The following sections were updated for better clarity: - Inclusion criteria. - Exclusion criteria. - Schedule of Events. - PK assessment. - PD assessment - Study Treatments: Updated dosage strength, deleted 50 mg and 200 mg strength capsules, now only 100 mg capsules will be used. Accordingly, dosing scheme also updated. • Updated some definitions. • Added ‘Grade 5 Fatal’ intensity under section for assessment of severity of AEs. • Subgroup of geographic region has been added. • Appendices were updated or added (eg, to provide details of list of excluded drugs, to provide details regarding efficacy assessments, etc).

08 Feb 2019

• Exclusion criteria related to TB was updated. • Local urine pregnancy test was added for Visits 2 to 7 for WOCBP. • Pregnancy-related text was updated to clarify that if a female subject became pregnant, she must discontinue study drug immediately. Also, it was clarified that subjects must be counseled during the informed consent process to inform the investigator of any pregnancy that occurred during study participation and for 6 months after the last dose of study drug. • On Day 1, the physical examination was updated from brief to complete. • Text related to PK and PD blood sample processing was updated. • Oracle™ Clinical Remote Data Capture was deleted throughout and Medidata Rave was added for consistency. • Appendices were updated.

03 Apr 2020

• Updated Inclusion and exclusion criteria • Study Design: As per request from Serbian authority, additional language has been added in Section 3.1.Updated safety variables to include tympanic temperature measurement for Korean subjects. Details of randomization visit (Study Day 1) has been updated and provided clarification for PK/PD subsets. • Updated guidelines for dose interruption and reduction. • Updated content of placebo capsules. • Removed the requirement about promptly reporting any overdose with or without associated AEs to the PPD Drug Safety Center. • csDMARDs dose stability during wash-out is not applicable. • Known CYP1A2 and UGT1A1 inhibitors and inducers must be prohibited for 4 weeks or 5 half-lives (whichever is longer), prior to Day 1 dosing. • Updates Schedule of Events. • Removed assessment of carbon dioxide in serum chemistry. Updated urinalysis to remove turbidity assessment. • The requirements to be an Independent Joint Assessor were expanded. • Defined the 8 categories that will be assessed by the HAQ-DI. • All statistical tests will be 2-sided and performed using a 5% significance level, leading to 95% CIs (2-sided). • A mixed model repeat measure (MMRM) analysis will be used instead of ANCOVA for analysis of secondary endpoints. • Appendices were updated. There is also Protocol Amendment 04, Version 5.0 dated 19 Oct 2020.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported.

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Clinical trials

Clinical Trial Results:
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study to Evaluate the Efficacy and Safety of Oral SKI-O-703 in Patients With Active Rheumatoid Arthritis Despite Treatment With Conventional Therapies

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Analysis of Change from Baseline in DAS28-hsCRP at Week 12

Primary: Analysis of Change from Baseline in DAS28-hsCRP at Week 12

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

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Clinical trials

Clinical Trial Results: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study to Evaluate the Efficacy and Safety of Oral SKI-O-703 in Patients With Active Rheumatoid Arthritis Despite Treatment With Conventional Therapies

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Analysis of Change from Baseline in DAS28-hsCRP at Week 12

Primary: Analysis of Change from Baseline in DAS28-hsCRP at Week 12

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study to Evaluate the Efficacy and Safety of Oral SKI-O-703 in Patients With Active Rheumatoid Arthritis Despite Treatment With Conventional Therapies