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Clinical Trial Results:
A Phase 2b, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Protocol to Evaluate the Safety and Efficacy of JNJ-64304500 in Subjects with Moderately to Severely Active Crohn’s Disease

Summary
EudraCT number	2016-000634-21
Trial protocol	DE GB HU PL FR IT
Global end of trial date	24 Jan 2022

Results information
Results version number	v1(current)
This version publication date	09 Feb 2023
First version publication date	09 Feb 2023
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

64304500CRD2001

ISRCTN number

US NCT number

NCT02877134

WHO universal trial number (UTN)

Sponsor organisation name

Janssen Research & Development, LLC

Sponsor organisation address

920 Route 202, South Raritan New Jersey, United States, 08869

Public contact

Clinical Registry Group, Janssen Research & Development LLC, ClinicalTrialsEU@its.jnj.com

Scientific contact

Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.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

24 Jan 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

24 Jan 2022

Was the trial ended prematurely?

Main objective of the trial

The main objective of the trial was to evaluate the efficacy of JNJ-64304500 to reduce the Crohn’s Disease Activity Index (CDAI) score from baseline and to evaluate the safety of JNJ-64304500.

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practice (GCP) and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

25 Aug 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 4

Country: Number of subjects enrolled

Bulgaria: 7

Country: Number of subjects enrolled

Germany: 12

Country: Number of subjects enrolled

France: 3

Country: Number of subjects enrolled

United Kingdom: 4

Country: Number of subjects enrolled

Hungary: 1

Country: Number of subjects enrolled

Italy: 13

Country: Number of subjects enrolled

Japan: 25

Country: Number of subjects enrolled

Korea, Republic of: 6

Country: Number of subjects enrolled

Poland: 72

Country: Number of subjects enrolled

Romania: 10

Country: Number of subjects enrolled

Russian Federation: 109

Country: Number of subjects enrolled

Ukraine: 80

Country: Number of subjects enrolled

United States: 42

Worldwide total number of subjects

388

EEA total number of subjects

122

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)

376

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

In subject disposition, data is reported in 2 periods, [Main Study” and “Part II LTE Phase”] depicts the information for the specified time period as: Part I: Through Week 38 (including safety follow-up); Part II: Through Week 24 for subjects who entered the LTE phase and through Week 36 for subjects who did not enter the LTE.

Screening details

A total of 388 subjects with moderately to severely active Crohn’s disease were randomised and treated. Of these, 304 completed main study phase and 95 completed long term extension (LTE) phase.

Period 1 title

Main Study (Parts I,II): Up to Week 38

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Part I: Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects were administered with Placebo subcutaneous injection on Weeks 0, 2, 4, 6, 8, 10. Subjects in clinical response at Week 12 continued to receive placebo every 2 weeks (Q2W) from Week 12 through Week 22.

Investigational medicinal product name

JNJ-64304500

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects not in clinical response at Week 12 were administered with JNJ-64304500 400 mg SC at Week 12 and then 200 mg SC Q2W from Week 14 through Week 22.

Part I: JNJ-64304500

Arm description

Subjects received JNJ-64304500 400 mg SC at Week 0 then 200 mg SC every two weeks through Week 22. All subjects were followed up for safety up to Week 38.

Arm type

Experimental

Investigational medicinal product name

JNJ-64304500

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects were administered with JNJ-64304500 400 mg SC injection at Week 0 then 200 mg SC every two weeks through Week 22.

Part II: Placebo

Arm description

Subjects received placebo SC at Weeks 0, 2, 4, and 8. Subjects in clinical response at Week 12 continued to receive placebo at Weeks 12, 14, 16, and 20. Subjects not in clinical response at Week 12 received JNJ-64304500 150 mg SC at Week 12 and then JNJ-64304500 75 mg SC at Weeks 14, 16, and 20. Subjects who completed Part II Week 24 assessments and who were benefited from continued treatment, in the opinion of the investigator, were eligible to enter the Part II long term extension (LTE) phase at Week 24. Subjects who did not enter into LTE phase at Week 24 were followed up for safety up to Week 36.

Arm type

Placebo

Investigational medicinal product name

JNJ-64304500

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects not in clinical response at Week 12 were administered with JNJ-64304500 150 mg SC at Week 12 and then JNJ-64304500 75 mg SC at Weeks 14, 16, and 20.

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects were administered with placebo SC injection at Weeks 0, 2, 4, and 8. Subjects in clinical response at Week 12 continued to receive placebo at Weeks 12, 14, 16, and 20.

Part II: JNJ-64304500 Low Dose

Arm description

Subjects received JNJ-64304500 50 mg SC at Week 0 and 25 mg SC at Weeks 2 and 4, then 25 mg SC every four weeks through Week 20. Subjects who completed Part II Week 24 assessments and who were benefited from continued treatment, in the opinion of the investigator, were eligible to enter the Part II LTE phase at Week 24. Subjects who did not enter into LTE phase at Week 24 were followed up for safety up to Week 36.

Arm type

Experimental

Investigational medicinal product name

JNJ-64304500

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects were administered with JNJ-64304500 50 mg SC at Week 0 and 25 mg SC at Weeks 2 and 4, then 25 mg SC every four weeks through Week 20.

Part II: JNJ-64304500 Middle Dose

Arm description

Subjects received JNJ-64304500 150 mg SC at Week 0 and 75 mg SC at Weeks 2 and 4, then 75 mg SC every four weeks through Week 20. Subjects who completed Part II Week 24 assessments and who were benefited from continued treatment, in the opinion of the investigator, were eligible to enter the Part II LTE phase at Week 24. Subjects who did not enter into LTE phase at Week 24 were followed up for safety up to Week 36.

Arm type

Experimental

Investigational medicinal product name

JNJ-64304500

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects were administered with JNJ-64304500 150 mg SC at Week 0 and 75 mg SC at Weeks 2 and 4, then 75 mg SC every four weeks through Week 20.

Part II: JNJ-64304500 High Dose

Arm description

Subjects received JNJ-64304500 400 mg SC at Week 0 and 200 mg SC at Weeks 2 and 4, then 200 mg SC every four weeks through Week 20. Subjects who completed Part II Week 24 assessments and who were benefited from continued treatment, in the opinion of the investigator, were eligible to enter the Part II LTE phase at Week 24. Subjects who did not enter into LTE phase at Week 24 were followed up for safety up to Week 36.

Arm type

Experimental

Investigational medicinal product name

JNJ-64304500

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects were administered with JNJ-64304500 400 mg SC at Week 0 and 200 mg SC at Weeks 2 and 4, then 200 mg SC every four weeks through Week 20.

Part II: Ustekinumab

Arm description

Subjects received Ustekinumab (tiered doses approximating 6 milligrams/kilograms (mg/kg) intravenously [IV]) at Week 0 (as indicated in the bullets below), followed by 90 mg SC at Weeks 8 and 16. - Ustekinumab 260 mg (weight [less than or equal to [<=] 55 kg). - Ustekinumab 390 mg (weight greater than [>] 55 kg and less than or equal to [<=] 85 kg). Ustekinumab 520 mg (weight >85 kg). Subjects who completed Part II Week 24 assessments and who were benefited from continued treatment, in the opinion of the investigator, were eligible to enter the Part II LTE phase at Week 24. Subjects who did not enter into LTE phase at Week 24 were followed up for safety up to Week 36.

Arm type

Experimental

Investigational medicinal product name

Ustekinumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects received Ustekinumab (tiered doses approximating 6 mg/kg IV at Week 0 (as indicated in the bullets below), followed by 90 mg SC at Weeks 8 and 16. - Ustekinumab 260 mg (weight <=55 kg). - Ustekinumab 390 mg (weight >55 kg and <=85 kg). - Ustekinumab 520 mg (weight >85 kg).

Number of subjects in period 1	Part I: Placebo	Part I: JNJ-64304500	Part II: Placebo	Part II: JNJ-64304500 Low Dose	Part II: JNJ-64304500 Middle Dose	Part II: JNJ-64304500 High Dose	Part II: Ustekinumab
Started	72	73	48	50	49	49	47
Placebo Non Responders at Week 12	44 ^[1]	0 ^[2]	31 ^[3]	0 ^[4]	0 ^[5]	0 ^[6]	0 ^[7]
Completed	58	48	40	35	42	39	42
Not completed	14	25	8	15	7	10	5
Death	-	1	-	-	-	1	-
Unspecified	1	1	3	6	4	3	2
Lost to follow-up	-	4	-	1	-	-	1
Withdrawal by subject	13	19	5	8	3	6	2

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only placebo non responders at Week 12 were reported.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only placebo non responders at Week 12 were reported.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only placebo non responders at Week 12 were reported.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only placebo non responders at Week 12 were reported.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only placebo non responders at Week 12 were reported.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only placebo non responders at Week 12 were reported.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Only placebo non responders at Week 12 were reported.

Period 2 title

Part II LTE Phase: From Week 24-88

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part II LTE: Placebo

Arm description

Subjects randomized to placebo group and who were benefitted from continued treatment in the opinion of the investigator, entered the Part II LTE phase and received placebo or JNJ-64304500 middle dose (JNJ-64304500 75 mg SC) at Weeks 24, 28, 32, 36, 40, 44, 48, 52 56, 60, 64, 68, and 72. Subjects were followed up for safety up to Week 88.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects were administered with placebo SC at Weeks 24, 28, 32, 36, 40, 44, 48, 52 56, 60, 64, 68, and 72.

Part II LTE: JNJ-64304500 Low Dose

Arm description

Subjects randomized to the ‘JNJ-64304500 Low Dose’ group and who were benefitted from continued treatment in the opinion of the investigator, entered the Part II LTE phase and received JNJ-64304500 25 mg SC at Weeks 24, 28, 32, 36, 40, 44, 48, 52 56, 60, 64, 68, and 72. Subjects were followed up for safety up to Week 88.

Arm type

Experimental

Investigational medicinal product name

JNJ-64304500

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects were administered with JNJ-64304500 25 mg SC at Weeks 24, 28, 32, 36, 40, 44, 48, 52 56, 60, 64, 68, and 72.

Part II LTE: JNJ-64304500 Middle Dose

Arm description

Subjects randomized to the ‘JNJ-64304500 Middle Dose’ group and who were benefitted from continued treatment in the opinion of the investigator, entered the Part II LTE phase and received JNJ-64304500 75 mg SC at Weeks 24, 28, 32, 36, 40, 44, 48, 52 56, 60, 64, 68, and 72. Subjects were followed up for safety up to Week 88.

Arm type

Experimental

Investigational medicinal product name

JNJ-64304500

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects were administered with JNJ-64304500 75 mg SC at Weeks 24, 28, 32, 36, 40, 44, 48, 52 56, 60, 64, 68, and 72.

Part II LTE: JNJ-64304500 High Dose

Arm description

Subjects randomized to the ‘JNJ-64304500 High Dose’ group and who were benefitted from continued treatment in the opinion of the investigator, entered the Part II LTE phase and received JNJ-64304500 200 mg SC at Weeks 24, 28, 32, 36, 40, 44, 48, 52 56, 60, 64, 68, and 72. Subjects were followed up for safety up to Week 88.

Arm type

Experimental

Investigational medicinal product name

JNJ-64304500

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intravenous use

Dosage and administration details

Subjects were administered with JNJ-64304500 200 mg SC at Weeks 24, 28, 32, 36, 40, 44, 48, 52 56, 60, 64, 68, and 72.

Part II LTE: Ustekinumab

Arm description

Subjects randomized to the ‘Ustekinumab’ group and who were benefitted from continued treatment in the opinion of the investigator, entered the Part II LTE phase and received Ustekinumab 90 mg IV at Weeks 24, 32, 40, 48, 56, 64 and 72. Subjects were followed up for safety up to Week 88.

Arm type

Experimental

Investigational medicinal product name

JNJ-64304500

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use, Intravenous use

Dosage and administration details

Subjects were administered with Ustekinumab 90 mg IV at Weeks 24, 32, 40, 48, 56, 64 and 72.

Number of subjects in period 2 ^[8]	Part II LTE: Placebo	Part II LTE: JNJ-64304500 Low Dose	Part II LTE: JNJ-64304500 Middle Dose	Part II LTE: JNJ-64304500 High Dose	Part II LTE: Ustekinumab
Started	22	21	27	24	28
Completed	20	17	20	14	24
Not completed	2	4	7	10	4
Not specified	-	-	3	1	1
Study terminated by sponsor	1	1	1	-	-
Lost to follow-up	-	1	-	-	-
Withdrawal by subject	1	2	3	9	3

Notes
[8] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Only eligible subjects from main study phase, entered into Part II LTE phase.

Baseline characteristics

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Reporting group title

Part I: Placebo

Reporting group description

Reporting group title

Part I: JNJ-64304500

Reporting group description

Subjects received JNJ-64304500 400 mg SC at Week 0 then 200 mg SC every two weeks through Week 22. All subjects were followed up for safety up to Week 38.

Reporting group title

Part II: Placebo

Reporting group description

Reporting group title

Part II: JNJ-64304500 Low Dose

Reporting group description

Reporting group title

Part II: JNJ-64304500 Middle Dose

Reporting group description

Reporting group title

Part II: JNJ-64304500 High Dose

Reporting group description

Reporting group title

Part II: Ustekinumab

Reporting group description

Reporting group values	Part I: Placebo	Part I: JNJ-64304500	Part II: Placebo	Part II: JNJ-64304500 Low Dose	Part II: JNJ-64304500 Middle Dose	Part II: JNJ-64304500 High Dose	Part II: Ustekinumab	Total
Number of subjects	72	73	48	50	49	49	47	388
Title for AgeCategorical
Units: subjects
Children (2-11 years)	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0
Adults (18-64 years)	71	70	45	48	47	49	46	376
From 65 to 84 years	1	3	3	2	2	0	1	12
85 years and over	0	0	0	0	0	0	0	0
Title for AgeContinuous
Units: years
arithmetic mean (standard deviation)	38.9 ( 13.3 )	38 ( 13.25 )	40.6 ( 13.69 )	36.4 ( 11.14 )	37.1 ( 15.04 )	37.2 ( 12.87 )	42 ( 12.62 )	-
Title for Gender
Units: subjects
Female	31	33	24	16	27	20	23	174
Male	41	40	24	34	22	29	24	214

End points

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Reporting group title

Part I: Placebo

Reporting group description

Reporting group title

Part I: JNJ-64304500

Reporting group description

Subjects received JNJ-64304500 400 mg SC at Week 0 then 200 mg SC every two weeks through Week 22. All subjects were followed up for safety up to Week 38.

Reporting group title

Part II: Placebo

Reporting group description

Reporting group title

Part II: JNJ-64304500 Low Dose

Reporting group description

Reporting group title

Part II: JNJ-64304500 Middle Dose

Reporting group description

Reporting group title

Part II: JNJ-64304500 High Dose

Reporting group description

Reporting group title

Part II: Ustekinumab

Reporting group description

Reporting group title

Part II LTE: Placebo

Reporting group description

Reporting group title

Part II LTE: JNJ-64304500 Low Dose

Reporting group description

Reporting group title

Part II LTE: JNJ-64304500 Middle Dose

Reporting group description

Reporting group title

Part II LTE: JNJ-64304500 High Dose

Reporting group description

Reporting group title

Part II LTE: Ustekinumab

Reporting group description

Primary: Part I: Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 8

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End point title

Part I: Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 8 ^[1] ^[2]

End point description

The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 8 different Crohn’s disease-related variables. The CDAI score was assessed by collecting information on 8 different Crohn’s disease-related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s), and/or opiates, and general well-being. The last 4 variables were scored over 7 days by the subject on a diary card. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. The efficacy analyses were based on the Full analysis set (FAS) included all randomised subjects in Part 1 who received at least 1 dose of study agent.

End point type

Primary

End point timeframe

Baseline to Week 8

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics was done, no inferential statistical analysis was performed.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Part I: Placebo	Part I: JNJ-64304500
Number of subjects analysed	72	73
Units: units on a scale
arithmetic mean (standard deviation)	-60.0 ( 77.08 )	-103.6 ( 93.54 )

No statistical analyses for this end point

Primary: Part II: Change From Baseline in the CDAI Score at Week 12

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End point title

Part II: Change From Baseline in the CDAI Score at Week 12 ^[3] ^[4]

End point description

The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 8 different Crohn’s disease-related variables. The CDAI was assessed by collecting information on 8 different Crohn's disease-related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being. The last 4 variables are scored over 7 days by the subject on a diary card. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. FAS included all randomised subjects in Part II who received at least 1 dose of study agent. Here 'N' (Number of subjects analysed) refers to number of subjects analysed for this endpoint.

End point type

Primary

End point timeframe

Baseline to Week 12

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics was done, no inferential statistical analysis was performed.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Part II: Placebo	Part II: JNJ-64304500 Low Dose	Part II: JNJ-64304500 Middle Dose	Part II: JNJ-64304500 High Dose	Part II: Ustekinumab
Number of subjects analysed	46	44	47	48	47
Units: units on a scale
arithmetic mean (standard deviation)	-59.2 ( 89.51 )	-93.2 ( 117.91 )	-72.2 ( 92.79 )	-84.3 ( 103.28 )	-148.8 ( 84.59 )

No statistical analyses for this end point

Secondary: Part II: Percentage of Subjects in Clinical Remission at Week 12 as Measured by CDAI (CDAI Less than [<] 150)

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End point title

Part II: Percentage of Subjects in Clinical Remission at Week 12 as Measured by CDAI (CDAI Less than [<] 150) ^[5]

End point description

Clinical Remission was defined as a CDAI score of <150 point. The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 8 different Crohn’s disease-related variables. extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. FAS included all randomised subjects in Part II who received at least 1 dose of study agent.

End point type

Secondary

End point timeframe

Week 12

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Part II: Placebo	Part II: JNJ-64304500 Low Dose	Part II: JNJ-64304500 Middle Dose	Part II: JNJ-64304500 High Dose	Part II: Ustekinumab
Number of subjects analysed	48	50	49	49	47
Units: percentage of subjects
number (not applicable)	14.6	30	18.4	22.4	53.2

No statistical analyses for this end point

Secondary: Part II: Percentage of Subjects in Clinical Response at Week 12 as Measured by CDAI (Greater than or Equal to [>=] 100-point Reduction from Baseline in CDAI or CDAI <150)

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End point title

Part II: Percentage of Subjects in Clinical Response at Week 12 as Measured by CDAI (Greater than or Equal to [>=] 100-point Reduction from Baseline in CDAI or CDAI <150) ^[6]

End point description

Clinical response was defined as a >=100-point reduction from the baseline CDAI score, or a CDAI score <150. The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. The CDAI is a validated multi-item measure of severity of illness derived as a weighted sum of 8 different Crohn’s disease-related variables. extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being. The CDAI score is used to quantify the symptoms of subjects with Crohn's Disease. A decrease in CDAI over time indicates improvement in disease activity. In general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities. FAS included all randomised subjects in Part II who received at least 1 dose of study agent.

End point type

Secondary

End point timeframe

Week 12

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Part II: Placebo	Part II: JNJ-64304500 Low Dose	Part II: JNJ-64304500 Middle Dose	Part II: JNJ-64304500 High Dose	Part II: Ustekinumab
Number of subjects analysed	48	50	49	49	47
Units: percentage of subjects
number (not applicable)	22.9	42.0	40.8	30.6	72.3

No statistical analyses for this end point

Secondary: Part II: Change from Baseline in Patient-Reported Outcome (PRO)-2 at Week 12

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End point title

Part II: Change from Baseline in Patient-Reported Outcome (PRO)-2 at Week 12 ^[7]

End point description

The PRO-2 score is defined as the sum of the abdominal pain and stool frequency components of the CDAI. PRO-2 scores ranges from 0 to approximately 300, higher score indicates higher disease activity. FAS included all randomised subjects in Part II who received at least 1 dose of study agent. Here 'N' (Number of subjects analysed) refers to number of subjects analysed for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Part II: Placebo	Part II: JNJ-64304500 Low Dose	Part II: JNJ-64304500 Middle Dose	Part II: JNJ-64304500 High Dose	Part II: Ustekinumab
Number of subjects analysed	46	44	47	48	46
Units: units on scale
arithmetic mean (standard deviation)	-28.8 ( 47.72 )	-46.1 ( 59.14 )	-39.8 ( 52.59 )	-42.9 ( 47.33 )	-70.1 ( 52.97 )

No statistical analyses for this end point

Secondary: Part II: Percentage of Subjects in Clinical remission at Week 12 as measured by PRO-2 (PRO-2 <75)

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End point title

Part II: Percentage of Subjects in Clinical remission at Week 12 as measured by PRO-2 (PRO-2 <75) ^[8]

End point description

Clinical remission was defined as a PRO-2 score of <75 point. FAS included all randomised subjects in Part II who received at least 1 dose of study agent. FAS included all randomised subjects in Part II who received at least 1 dose of study agent.

End point type

Secondary

End point timeframe

Week 12

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Part II: Placebo	Part II: JNJ-64304500 Low Dose	Part II: JNJ-64304500 Middle Dose	Part II: JNJ-64304500 High Dose	Part II: Ustekinumab
Number of subjects analysed	48	50	49	49	47
Units: percentage of subjects
number (not applicable)	16.7	32.0	30.6	44.9	53.2

No statistical analyses for this end point

Secondary: Part II: Percentage of Subjects in Clinical response at Week 12 as measured by PRO-2 (>=50-point reduction from baseline in PRO-2 Score or PRO-2 Score <75)

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End point title

Part II: Percentage of Subjects in Clinical response at Week 12 as measured by PRO-2 (>=50-point reduction from baseline in PRO-2 Score or PRO-2 Score <75) ^[9]

End point description

Clinical response was defined as >=50-point reduction from baseline in PRO-2 or Score or PRO-2 Score <75. FAS included all randomised subjects in Part II who received at least 1 dose of study agent.

End point type

Secondary

End point timeframe

Week 12

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Part II: Placebo	Part II: JNJ-64304500 Low Dose	Part II: JNJ-64304500 Middle Dose	Part II: JNJ-64304500 High Dose	Part II: Ustekinumab
Number of subjects analysed	48	50	49	49	47
Units: percentage of subjects
number (not applicable)	31.3	44.0	46.9	49.0	68.1

No statistical analyses for this end point

Secondary: Part II: Change from Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12

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End point title

Part II: Change from Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12 ^[10]

End point description

SES-CD is a validated instrument reflecting an endoscopist global appraisal of mucosal lesions in Crohn's disease. SES-CD grades lesions by location (5 bowel segments: ileum, right colon, transverse colon, left colon, and rectum) using 4 endoscopic variables: ulcer size, extent of ulcerated surface, extent of affected surface, and presence/type of narrowing. The total SES-CD was calculated as the sum of the 4 variables for the 5 bowel segments: rectum, left colon, transverse colon, right colon, and ileum. Scores range from 0 to 60, with higher scores indicating more severe disease. FAS included all randomised subjects in Part II who received at least 1 dose of study agent. Here 'N' (Number of subjects analysed) refers to number of subjects analysed for this endpoint.

End point type

Secondary

End point timeframe

Baseline, Week 12

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint was planned to be analyzed for specified arms only.

End point values	Part II: Placebo	Part II: JNJ-64304500 Low Dose	Part II: JNJ-64304500 Middle Dose	Part II: JNJ-64304500 High Dose	Part II: Ustekinumab
Number of subjects analysed	34	33	33	38	36
Units: units on a scale
arithmetic mean (standard deviation)	-2.2 ( 6.58 )	-0.7 ( 6.47 )	-1.2 ( 4.89 )	-2.7 ( 6.93 )	-2.6 ( 5.32 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Part I: Through Week 38; Part II: Through Week 24 for subjects who entered the LTE and through Week 36 for subjects who did not enter the LTE; Part II LTE: from Week 24 through Week 88

Adverse event reporting additional description

The safety analysis set included all randomised subjects who received at least 1 dose of study agent (placebo or JNJ-64304500 or ustekinumab, including a partial dose).

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

Part I: Placebo

Reporting group description

Subjects received placebo subcutaneously (SC) at Weeks 0, 2, 4, 6, 8, and 10. Subjects in clinical response at Week 12 continued to receive placebo every 2 weeks (Q2W) through Week 22. Subjects not in clinical response at Week 12 received JNJ-64304500 400 mg SC at Week 12 and then 200 mg SC Q2W from Week 14 through Week 22. Safety results included data up to the time of receiving JNJ-64304500 for those who received JNJ-64304500 at Week 12 and included all data for those who did not receive JNJ-64304500 at Week 12. Subjects were followed up for safety up to Week 38.

Reporting group title

Part I: Placebo to JNJ-64304500

Reporting group description

Subjects received placebo SC at Weeks 0, 2, 4, 6, 8, and 10. Subjects in clinical response at Week 12 continued to receive placebo Q2W through Week 22. Subjects not in clinical response at Week 12 received JNJ-64304500 400 mg SC at Week 12 and then 200 mg SC Q2W from Week 14 through Week 22. Safety results included data from the time of receiving JNJ- 64304500 at Week 12 onward. Subjects were followed up for safety up to Week 38.

Reporting group title

Part I: JNJ-64304500

Reporting group description

Subjects received JNJ-64304500 400 mg SC at Week 0 then 200 mg SC every two weeks through Week 22. Subjects were followed up for safety up to Week 38.

Reporting group title

Part II: Placebo

Reporting group description

Subjects received placebo SC at Weeks 0, 2, 4, and 8. Subjects in clinical response at Week 12 continued to receive placebo at Weeks 12, 14, 16, and 20. Subjects not in clinical response at Week 12 received JNJ 64304500 150 mg SC at Week 12 and then JNJ-64304500 75 mg SC at Weeks 14, 16, and 20. Safety results included data up to the time of receiving JNJ- 64304500 for those who received JNJ-64304500 at Week 12 and included all data for those who did not receive JNJ-64304500 at Week 12. Subjects who completed Part II Week 24 assessments and who were benefited from continued treatment, in the opinion of the investigator, were eligible to enter the Part II LTE phase at Week 24. Subjects who did not enter into LTE phase at Week 24 were followed up for safety up to Week 36.

Reporting group title

Part II: Placebo to JNJ-64304500 Middle Dose

Reporting group description

Subjects received placebo SC at Weeks 0, 2, 4, and 8. Subjects in clinical response at Week 12 continued to receive placebo at Weeks 12, 14, 16, and 20. Subjects not in clinical response at Week 12 received JNJ 64304500 150 mg SC at Week 12 and then JNJ-64304500 75 mg SC at Weeks 14, 16, and 20. Safety results included data from the time of receiving JNJ- 64304500 at Week 12 onward. Subjects who completed Part II Week 24 assessments and who were benefited from continued treatment, in the opinion of the investigator, were eligible to enter the Part II LTE phase at Week 24. Subjects who did not enter into LTE phase at Week 24 were followed up for safety up to Week 36.

Reporting group title

Part II: JNJ-64304500 Low Dose

Reporting group description

Reporting group title

Part II: JNJ-64304500 Middle Dose

Reporting group description

Reporting group title

Part II: JNJ-64304500 High Dose

Reporting group description

Reporting group title

Part II: Ustekinumab

Reporting group description

Reporting group title

Part II LTE: Placebo

Reporting group description

Subjects randomized to the 'Placebo' group and who were benefitted from continued treatment in the opinion of the investigator, entered the Part II LTE phase and received placebo at Weeks 24, 28, 32, 36, 40, 44, 48, 52 56, 60, 64, 68, and 72. Subjects were followed up to Week 88 for safety.

Reporting group title

Part II LTE: Placebo to JNJ-64304500 Middle Dose

Reporting group description

Subjects randomized to placebo group and had dose adjustment to JNJ-64304500 middle dose at Week 12, continued to receive JNJ-64304500 middle dose (received JNJ-64304500 75 mg SC) at Weeks 24, 28, 32, 36, 40, 44, 48, 52 56, 60, 64, 68, and 72 in the Part II LTE. Subjects were followed up for safety up to Week 88.

Reporting group title

Part II LTE: JNJ-64304500 Low Dose

Reporting group description

Reporting group title

Part II LTE: JNJ-64304500 Middle Dose

Reporting group description

Reporting group title

Part II LTE: JNJ-64304500 High Dose

Reporting group description

Reporting group title

Part II LTE: Ustekinumab

Reporting group description

Subjects randomized to ‘Ustekinumab’ group and who were benefitted from continued treatment in the opinion of the investigator, entered the Part II LTE phase and received Ustekinumab 90 mg IV at Weeks 24, 32, 40, 48, 56, 64 and 72. Subjects were followed up for safety up to Week 88.

Part I: Placebo

Part I: Placebo to JNJ-64304500

Part I: JNJ-64304500

Part II: Placebo

Part II: Placebo to JNJ-64304500 Middle Dose

Part II: JNJ-64304500 Low Dose

Part II: JNJ-64304500 Middle Dose

Part II: JNJ-64304500 High Dose

Part II: Ustekinumab

Part II LTE: Placebo

Part II LTE: Placebo to JNJ-64304500 Middle Dose

Part II LTE: JNJ-64304500 Low Dose

Part II LTE: JNJ-64304500 Middle Dose

Part II LTE: JNJ-64304500 High Dose

Part II LTE: Ustekinumab

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 72 (1.39%)

2 / 44 (4.55%)

8 / 73 (10.96%)

3 / 48 (6.25%)

0 / 31 (0.00%)

3 / 50 (6.00%)

0 / 49 (0.00%)

6 / 49 (12.24%)

2 / 47 (4.26%)

1 / 10 (10.00%)

3 / 12 (25.00%)

2 / 21 (9.52%)

5 / 27 (18.52%)

5 / 24 (20.83%)

5 / 28 (17.86%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Benign Ovarian Tumour

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 47 (2.13%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Squamous Cell Carcinoma

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

1 / 28 (3.57%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Uterine Leiomyoma

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Deep Vein Thrombosis

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 49 (2.04%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Death

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 49 (2.04%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Reproductive system and breast disorders

Ovarian Cyst Ruptured

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Pulmonary Embolism

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 49 (2.04%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Depression Suicidal

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 49 (2.04%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Lipase Increased

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

1 / 50 (2.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Hand Fracture

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Radius Fracture

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute Myocardial Infarction

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

1 / 27 (3.70%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac Arrest

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

1 / 73 (1.37%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Myocardial Infarction

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

1 / 73 (1.37%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Headache

subjects affected / exposed

1 / 72 (1.39%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

1 / 73 (1.37%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

1 / 28 (3.57%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal Pain

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

1 / 10 (10.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Crohn's Disease

subjects affected / exposed

0 / 72 (0.00%)

1 / 44 (2.27%)

5 / 73 (6.85%)

1 / 48 (2.08%)

0 / 31 (0.00%)

1 / 50 (2.00%)

0 / 49 (0.00%)

2 / 49 (4.08%)

1 / 47 (2.13%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 21 (4.76%)

4 / 27 (14.81%)

0 / 24 (0.00%)

1 / 28 (3.57%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 7

1 / 1

0 / 0

0 / 1

0 / 0

1 / 2

0 / 1

0 / 0

0 / 1

0 / 4

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Ileal Perforation

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

1 / 48 (2.08%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileal Stenosis

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

1 / 28 (3.57%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ileus

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

1 / 12 (8.33%)

0 / 21 (0.00%)

0 / 27 (0.00%)

1 / 24 (4.17%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Large Intestine Perforation

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

1 / 48 (2.08%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small Intestinal Obstruction

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

1 / 50 (2.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small Intestinal Stenosis

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

1 / 28 (3.57%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Acute Hepatic Failure

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

1 / 73 (1.37%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholecystitis

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

1 / 49 (2.04%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

1 / 24 (4.17%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Foot Deformity

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

1 / 24 (4.17%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Anal Abscess

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

1 / 50 (2.00%)

0 / 49 (0.00%)

1 / 49 (2.04%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

3 / 24 (12.50%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 6

0 / 0

deaths causally related to treatment / all

0 / 0

Device Related Sepsis

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

1 / 73 (1.37%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

1 / 73 (1.37%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis Viral

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

1 / 73 (1.37%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peritonitis

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

1 / 28 (3.57%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Salmonellosis

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

1 / 27 (3.70%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

1 / 73 (1.37%)

1 / 48 (2.08%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary Tract Infection Bacterial

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

1 / 21 (4.76%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Hypokalaemia

subjects affected / exposed

0 / 72 (0.00%)

1 / 44 (2.27%)

0 / 73 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malnutrition

subjects affected / exposed

0 / 72 (0.00%)

0 / 44 (0.00%)

1 / 73 (1.37%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 50 (0.00%)

0 / 49 (0.00%)

0 / 47 (0.00%)

0 / 10 (0.00%)

0 / 12 (0.00%)

0 / 21 (0.00%)

0 / 27 (0.00%)

0 / 24 (0.00%)

0 / 28 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part I: Placebo	Part I: Placebo to JNJ-64304500	Part I: JNJ-64304500	Part II: Placebo	Part II: Placebo to JNJ-64304500 Middle Dose	Part II: JNJ-64304500 Low Dose	Part II: JNJ-64304500 Middle Dose	Part II: JNJ-64304500 High Dose	Part II: Ustekinumab	Part II LTE: Placebo	Part II LTE: Placebo to JNJ-64304500 Middle Dose	Part II LTE: JNJ-64304500 Low Dose	Part II LTE: JNJ-64304500 Middle Dose	Part II LTE: JNJ-64304500 High Dose	Part II LTE: Ustekinumab
Total subjects affected by non serious adverse events
subjects affected / exposed	24 / 72 (33.33%)	10 / 44 (22.73%)	38 / 73 (52.05%)	16 / 48 (33.33%)	6 / 31 (19.35%)	24 / 50 (48.00%)	23 / 49 (46.94%)	26 / 49 (53.06%)	20 / 47 (42.55%)	5 / 10 (50.00%)	5 / 12 (41.67%)	6 / 21 (28.57%)	12 / 27 (44.44%)	10 / 24 (41.67%)	9 / 28 (32.14%)
Investigations
Blood Alkaline Phosphatase Increased
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	4 / 73 (5.48%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)	1 / 47 (2.13%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 21 (4.76%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	0	4	2	0	0	0	0	1	0	0	1	0	0	0
Lymphocyte Count Decreased
subjects affected / exposed	2 / 72 (2.78%)	0 / 44 (0.00%)	7 / 73 (9.59%)	1 / 48 (2.08%)	0 / 31 (0.00%)	2 / 50 (4.00%)	3 / 49 (6.12%)	1 / 49 (2.04%)	0 / 47 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 21 (4.76%)	0 / 27 (0.00%)	1 / 24 (4.17%)	0 / 28 (0.00%)
occurrences all number	2	0	7	1	0	2	3	1	0	1	0	1	0	1	0
Neutrophil Count Decreased
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	2 / 73 (2.74%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 50 (2.00%)	0 / 49 (0.00%)	1 / 49 (2.04%)	1 / 47 (2.13%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	1 / 27 (3.70%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	0	2	0	0	1	0	2	1	1	0	0	1	0	0
Platelet Count Increased
subjects affected / exposed	1 / 72 (1.39%)	0 / 44 (0.00%)	0 / 73 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 50 (2.00%)	4 / 49 (8.16%)	0 / 49 (0.00%)	2 / 47 (4.26%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	1 / 27 (3.70%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	1	0	0	0	0	1	5	0	2	1	0	0	2	0	0
Weight Decreased
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	0 / 73 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 50 (0.00%)	1 / 49 (2.04%)	0 / 49 (0.00%)	1 / 47 (2.13%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	2 / 28 (7.14%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	0	0	2
White Blood Cell Count Decreased
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	4 / 73 (5.48%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 50 (2.00%)	1 / 49 (2.04%)	1 / 49 (2.04%)	1 / 47 (2.13%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	0	5	0	0	1	1	1	1	1	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Inflammation
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	0 / 73 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)	0 / 47 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	5 / 72 (6.94%)	2 / 44 (4.55%)	8 / 73 (10.96%)	3 / 48 (6.25%)	0 / 31 (0.00%)	2 / 50 (4.00%)	4 / 49 (8.16%)	4 / 49 (8.16%)	5 / 47 (10.64%)	1 / 10 (10.00%)	1 / 12 (8.33%)	0 / 21 (0.00%)	1 / 27 (3.70%)	0 / 24 (0.00%)	2 / 28 (7.14%)
occurrences all number	7	3	11	3	0	2	5	4	5	1	1	0	1	0	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 72 (4.17%)	1 / 44 (2.27%)	9 / 73 (12.33%)	3 / 48 (6.25%)	0 / 31 (0.00%)	6 / 50 (12.00%)	7 / 49 (14.29%)	2 / 49 (4.08%)	1 / 47 (2.13%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 21 (0.00%)	3 / 27 (11.11%)	1 / 24 (4.17%)	2 / 28 (7.14%)
occurrences all number	3	1	16	4	0	7	8	2	1	0	1	0	3	2	2
Iron Deficiency Anaemia
subjects affected / exposed	2 / 72 (2.78%)	0 / 44 (0.00%)	1 / 73 (1.37%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 50 (0.00%)	1 / 49 (2.04%)	0 / 49 (0.00%)	0 / 47 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	2 / 28 (7.14%)
occurrences all number	2	0	1	0	1	0	1	0	0	0	0	0	0	0	2
Lymphopenia
subjects affected / exposed	1 / 72 (1.39%)	1 / 44 (2.27%)	4 / 73 (5.48%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 50 (2.00%)	3 / 49 (6.12%)	1 / 49 (2.04%)	0 / 47 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	1	2	5	0	0	1	3	1	0	0	0	0	0	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	4 / 72 (5.56%)	1 / 44 (2.27%)	1 / 73 (1.37%)	2 / 48 (4.17%)	0 / 31 (0.00%)	1 / 50 (2.00%)	1 / 49 (2.04%)	1 / 49 (2.04%)	0 / 47 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	1 / 27 (3.70%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	4	1	1	5	0	1	1	1	0	0	0	0	2	0	0
Pyrexia
subjects affected / exposed	1 / 72 (1.39%)	1 / 44 (2.27%)	3 / 73 (4.11%)	3 / 48 (6.25%)	1 / 31 (3.23%)	0 / 50 (0.00%)	2 / 49 (4.08%)	1 / 49 (2.04%)	2 / 47 (4.26%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	1 / 27 (3.70%)	2 / 24 (8.33%)	0 / 28 (0.00%)
occurrences all number	2	1	3	6	1	0	5	2	2	1	0	0	2	2	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	0 / 73 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 50 (2.00%)	0 / 49 (0.00%)	1 / 49 (2.04%)	1 / 47 (2.13%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	2 / 27 (7.41%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	0	0	0	0	2	0	1	1	0	0	0	2	0	0
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	3 / 72 (4.17%)	3 / 44 (6.82%)	5 / 73 (6.85%)	1 / 48 (2.08%)	1 / 31 (3.23%)	2 / 50 (4.00%)	1 / 49 (2.04%)	3 / 49 (6.12%)	5 / 47 (10.64%)	1 / 10 (10.00%)	0 / 12 (0.00%)	1 / 21 (4.76%)	0 / 27 (0.00%)	0 / 24 (0.00%)	2 / 28 (7.14%)
occurrences all number	3	4	5	2	7	2	1	4	8	1	0	1	0	0	2
Crohn's Disease
subjects affected / exposed	4 / 72 (5.56%)	0 / 44 (0.00%)	6 / 73 (8.22%)	4 / 48 (8.33%)	0 / 31 (0.00%)	4 / 50 (8.00%)	7 / 49 (14.29%)	2 / 49 (4.08%)	2 / 47 (4.26%)	1 / 10 (10.00%)	1 / 12 (8.33%)	1 / 21 (4.76%)	4 / 27 (14.81%)	2 / 24 (8.33%)	2 / 28 (7.14%)
occurrences all number	4	0	8	5	0	4	7	2	2	1	1	1	5	3	2
Diarrhoea
subjects affected / exposed	2 / 72 (2.78%)	1 / 44 (2.27%)	2 / 73 (2.74%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 50 (2.00%)	0 / 49 (0.00%)	1 / 49 (2.04%)	0 / 47 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	2 / 28 (7.14%)
occurrences all number	2	1	2	0	0	2	0	1	0	0	0	0	0	0	2
Enterovesical Fistula
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	0 / 73 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)	0 / 47 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Gastric Ulcer
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	0 / 73 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)	0 / 47 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Gastritis
subjects affected / exposed	0 / 72 (0.00%)	1 / 44 (2.27%)	0 / 73 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	1 / 49 (2.04%)	0 / 47 (0.00%)	1 / 10 (10.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	2	0	0	0	0	0	1	0	1	0	0	0	0	0
Gastrooesophageal Reflux Disease
subjects affected / exposed	1 / 72 (1.39%)	0 / 44 (0.00%)	1 / 73 (1.37%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	3 / 49 (6.12%)	0 / 47 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	1	0	1	1	0	0	0	3	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 72 (1.39%)	0 / 44 (0.00%)	3 / 73 (4.11%)	1 / 48 (2.08%)	0 / 31 (0.00%)	2 / 50 (4.00%)	1 / 49 (2.04%)	3 / 49 (6.12%)	1 / 47 (2.13%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 21 (4.76%)	0 / 27 (0.00%)	1 / 24 (4.17%)	0 / 28 (0.00%)
occurrences all number	1	0	4	1	0	2	1	4	1	0	0	2	0	1	0
Vomiting
subjects affected / exposed	1 / 72 (1.39%)	0 / 44 (0.00%)	3 / 73 (4.11%)	1 / 48 (2.08%)	0 / 31 (0.00%)	1 / 50 (2.00%)	0 / 49 (0.00%)	4 / 49 (8.16%)	0 / 47 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	1	0	4	1	0	1	0	5	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	1 / 72 (1.39%)	0 / 44 (0.00%)	0 / 73 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	3 / 49 (6.12%)	0 / 47 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	1 / 24 (4.17%)	0 / 28 (0.00%)
occurrences all number	1	0	0	0	0	0	0	3	0	0	0	0	0	1	0
Rash
subjects affected / exposed	0 / 72 (0.00%)	1 / 44 (2.27%)	2 / 73 (2.74%)	0 / 48 (0.00%)	0 / 31 (0.00%)	2 / 50 (4.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)	1 / 47 (2.13%)	0 / 10 (0.00%)	0 / 12 (0.00%)	2 / 21 (9.52%)	0 / 27 (0.00%)	0 / 24 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	1	2	0	0	2	0	0	2	0	0	2	0	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 72 (1.39%)	0 / 44 (0.00%)	1 / 73 (1.37%)	4 / 48 (8.33%)	0 / 31 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	2 / 49 (4.08%)	1 / 47 (2.13%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	1 / 27 (3.70%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	1	0	1	4	0	0	0	2	1	0	0	0	1	0	0
Back Pain
subjects affected / exposed	0 / 72 (0.00%)	1 / 44 (2.27%)	1 / 73 (1.37%)	0 / 48 (0.00%)	1 / 31 (3.23%)	1 / 50 (2.00%)	0 / 49 (0.00%)	1 / 49 (2.04%)	0 / 47 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 21 (4.76%)	1 / 27 (3.70%)	2 / 24 (8.33%)	0 / 28 (0.00%)
occurrences all number	0	1	1	0	1	1	0	1	0	0	0	2	1	2	0
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	0 / 73 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 50 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)	0 / 47 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	2 / 28 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Influenza
subjects affected / exposed	1 / 72 (1.39%)	1 / 44 (2.27%)	4 / 73 (5.48%)	1 / 48 (2.08%)	1 / 31 (3.23%)	0 / 50 (0.00%)	2 / 49 (4.08%)	0 / 49 (0.00%)	1 / 47 (2.13%)	0 / 10 (0.00%)	0 / 12 (0.00%)	1 / 21 (4.76%)	0 / 27 (0.00%)	1 / 24 (4.17%)	0 / 28 (0.00%)
occurrences all number	1	1	4	1	1	0	2	0	1	0	0	1	0	1	0
Nasopharyngitis
subjects affected / exposed	3 / 72 (4.17%)	2 / 44 (4.55%)	7 / 73 (9.59%)	2 / 48 (4.17%)	1 / 31 (3.23%)	3 / 50 (6.00%)	3 / 49 (6.12%)	4 / 49 (8.16%)	4 / 47 (8.51%)	0 / 10 (0.00%)	1 / 12 (8.33%)	1 / 21 (4.76%)	3 / 27 (11.11%)	1 / 24 (4.17%)	1 / 28 (3.57%)
occurrences all number	3	2	8	2	1	3	3	4	4	0	1	1	3	1	1
Rhinitis
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	0 / 73 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 50 (0.00%)	1 / 49 (2.04%)	5 / 49 (10.20%)	0 / 47 (0.00%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	0 / 28 (0.00%)
occurrences all number	0	0	0	0	1	0	1	5	0	0	0	0	0	0	0
Upper Respiratory Tract Infection
subjects affected / exposed	1 / 72 (1.39%)	0 / 44 (0.00%)	0 / 73 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	1 / 50 (2.00%)	2 / 49 (4.08%)	4 / 49 (8.16%)	1 / 47 (2.13%)	0 / 10 (0.00%)	0 / 12 (0.00%)	0 / 21 (0.00%)	0 / 27 (0.00%)	1 / 24 (4.17%)	1 / 28 (3.57%)
occurrences all number	1	0	0	1	0	1	3	4	1	0	0	0	0	1	1
Metabolism and nutrition disorders
Hypophosphataemia
subjects affected / exposed	0 / 72 (0.00%)	0 / 44 (0.00%)	0 / 73 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 50 (2.00%)	0 / 49 (0.00%)	1 / 49 (2.04%)	0 / 47 (0.00%)	0 / 10 (0.00%)	1 / 12 (8.33%)	0 / 21 (0.00%)	0 / 27 (0.00%)	0 / 24 (0.00%)	1 / 28 (3.57%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	1	0	0	0	1

More information

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Were there any global substantial amendments to the protocol? Yes

14 Jun 2016

-To add the collection of stool consistency data using the Bristol Stool Form Scale and assessment of abdominal pain based on the numerical rating scale, as well as exploratory analyses of these data. -To include an additional sample for anti-drug antibody analysis at Week 2 and to increase the frequency of efficacy and clinical laboratory assessments to all visits of the Main Study phase. -Text was revised to clarify that the sample size for Part II was based on the power to detect a dose-response signal and the sample size/power considerations for the pairwise comparisons of the JNJ-64304500 groups with placebo were based on the comparison of the high dose group with placebo.

09 Nov 2016

-To change the 12-week follow-up period after the last administration of study agent to a 16-week follow-up period. -To add the PGIS of Crohn’s disease and the PGIC of severity of Crohn’s disease as efficacy assessments in Part II of the study. -To add exploratory histologic assessments. -To add instructions regarding injection-site location to accurately assess potential injection-site reactions. -To update an inclusion criterion related to contraception to be in-line with the core safety information. -To update the inclusion criteria related to prior or current medications for Crohn’s disease to clarify the requirements for Part II.

12 Dec 2017

-To evaluate the efficacy and safety of JNJ-64304500 in a broader population, the subject population in Part II was changed to include both biologic intolerant or refractory (Bio-IR) and biologic nonfailure, that is, inadequate response to or failed to tolerate corticosteroids or immunomodulators, but not a biologic (Bio-NF) subjects. -To increase the sample size in Part II to 275 subjects to have sufficient power based on the amended Part II population.

24 Apr 2018

-To revise the study drug concentrations for the JNJ-64304500 low and middle doses in Part II of the study to correspond to the Investigational Product Preparation Instructions dilution regimen.

17 Jan 2019

-To reduce the sample size for Part II from 275 to 250 subjects. -To change the primary endpoint timing for Part II from Week 8 to Week 12, based on the results from the previous Part 1 Week 12 analysis. -To add a Part II LTE to provide longer term study drug access to eligible subjects for up to 52 weeks. -To clarify the exclusion and discontinuation criteria.

04 Feb 2020

-To adjust the maximum proportion of Bio-NF subjects to 60 percent (%) (from 50%), which allowed for additional enrollment flexibility, based upon observed enrollment patterns in Part II. The maximum proportion of Bio-IR subjects remained at 60%. The proposed change did not pose a risk to statistical power for Part II, as the power was based on overall population.

04 Jun 2021

-Part II of the study was unblinded due to lack of sufficient efficacy of JNJ-64304500 based on the Part II Week 12 analysis. The unblinding occurred after all Part II subjects completed their Week 24 assessments. -Subjects who were receiving JNJ-64304500 or placebo in the Part II LTE were discontinued. -Subjects receiving ustekinumab in countries where ustekinumab is not commercially available were continued in the LTE. To reduce the burden of the ustekinumab subjects who continue in the LTE, the laboratory assessments (including pharmacokinetic and immunogenicity) were removed, and the 16-week safety follow-up was removed due to the well-known safety profile of ustekinumab.

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 2b, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Protocol to Evaluate the Safety and Efficacy of JNJ-64304500 in Subjects with Moderately to Severely Active Crohn’s Disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part I: Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 8

Primary: Part I: Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 8

Primary: Part II: Change From Baseline in the CDAI Score at Week 12

Primary: Part II: Change From Baseline in the CDAI Score at Week 12

Secondary: Part II: Percentage of Subjects in Clinical Remission at Week 12 as Measured by CDAI (CDAI Less than [<] 150)

Secondary: Part II: Percentage of Subjects in Clinical Remission at Week 12 as Measured by CDAI (CDAI Less than [<] 150)

Secondary: Part II: Percentage of Subjects in Clinical Response at Week 12 as Measured by CDAI (Greater than or Equal to [>=] 100-point Reduction from Baseline in CDAI or CDAI <150)

Secondary: Part II: Percentage of Subjects in Clinical Response at Week 12 as Measured by CDAI (Greater than or Equal to [>=] 100-point Reduction from Baseline in CDAI or CDAI <150)

Secondary: Part II: Change from Baseline in Patient-Reported Outcome (PRO)-2 at Week 12

Secondary: Part II: Change from Baseline in Patient-Reported Outcome (PRO)-2 at Week 12

Secondary: Part II: Percentage of Subjects in Clinical remission at Week 12 as measured by PRO-2 (PRO-2 <75)

Secondary: Part II: Percentage of Subjects in Clinical remission at Week 12 as measured by PRO-2 (PRO-2 <75)

Secondary: Part II: Percentage of Subjects in Clinical response at Week 12 as measured by PRO-2 (>=50-point reduction from baseline in PRO-2 Score or PRO-2 Score <75)

Secondary: Part II: Percentage of Subjects in Clinical response at Week 12 as measured by PRO-2 (>=50-point reduction from baseline in PRO-2 Score or PRO-2 Score <75)

Secondary: Part II: Change from Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12

Secondary: Part II: Change from Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 2b, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Protocol to Evaluate the Safety and Efficacy of JNJ-64304500 in Subjects with Moderately to Severely Active Crohn’s Disease

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part I: Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 8

Primary: Part I: Change From Baseline in the Crohn's Disease Activity Index (CDAI) Score at Week 8

Primary: Part II: Change From Baseline in the CDAI Score at Week 12

Primary: Part II: Change From Baseline in the CDAI Score at Week 12

Secondary: Part II: Percentage of Subjects in Clinical Remission at Week 12 as Measured by CDAI (CDAI Less than [<] 150)

Secondary: Part II: Percentage of Subjects in Clinical Remission at Week 12 as Measured by CDAI (CDAI Less than [<] 150)

Secondary: Part II: Percentage of Subjects in Clinical Response at Week 12 as Measured by CDAI (Greater than or Equal to [>=] 100-point Reduction from Baseline in CDAI or CDAI <150)

Secondary: Part II: Percentage of Subjects in Clinical Response at Week 12 as Measured by CDAI (Greater than or Equal to [>=] 100-point Reduction from Baseline in CDAI or CDAI <150)

Secondary: Part II: Change from Baseline in Patient-Reported Outcome (PRO)-2 at Week 12

Secondary: Part II: Change from Baseline in Patient-Reported Outcome (PRO)-2 at Week 12

Secondary: Part II: Percentage of Subjects in Clinical remission at Week 12 as measured by PRO-2 (PRO-2 <75)

Secondary: Part II: Percentage of Subjects in Clinical remission at Week 12 as measured by PRO-2 (PRO-2 <75)

Secondary: Part II: Percentage of Subjects in Clinical response at Week 12 as measured by PRO-2 (>=50-point reduction from baseline in PRO-2 Score or PRO-2 Score <75)

Secondary: Part II: Percentage of Subjects in Clinical response at Week 12 as measured by PRO-2 (>=50-point reduction from baseline in PRO-2 Score or PRO-2 Score <75)

Secondary: Part II: Change from Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12

Secondary: Part II: Change from Baseline in Simple Endoscopic Score for Crohn's Disease (SES-CD) 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 2b, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Protocol to Evaluate the Safety and Efficacy of JNJ-64304500 in Subjects with Moderately to Severely Active Crohn’s Disease