Trial Outcomes & Findings for A Study of Efficacy and Safety of Ustekinumab in Patients With Primary Biliary Cirrhosis (PBC) Who Had an Inadequate Response to Ursodeoxycholic Acid (NCT NCT01389973)
NCT ID: NCT01389973
Last Updated: 2016-06-20
Results Overview
The ALP response was defined as a greater than 40 percent (%) decrease from Baseline in ALP concentration at Week 12.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Week 12
Results posted on
2016-06-20
Participant Flow
The study had 2 parts, Part 1 (proof of concept) and Part 2. As per the study design, the study was considered completed after part 1 and part 2 was not initiated. Results shown below are for Part 1 of the study.
Participant milestones
| Measure |
Open-label: Ustekinumab 90 mg
In proof of concept phase of Part 1, participants received ustekinumab 90 milligram (mg) subcutaneously at Week 0, 4 and thereafter every 8 weeks through Week 20. Eligible participants entered long-term extension which began at Week 28 and continued through Week 216.
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
20
|
Reasons for withdrawal
| Measure |
Open-label: Ustekinumab 90 mg
In proof of concept phase of Part 1, participants received ustekinumab 90 milligram (mg) subcutaneously at Week 0, 4 and thereafter every 8 weeks through Week 20. Eligible participants entered long-term extension which began at Week 28 and continued through Week 216.
|
|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Trial Stopped by Sponsor
|
9
|
|
Overall Study
Other
|
10
|
Baseline Characteristics
A Study of Efficacy and Safety of Ustekinumab in Patients With Primary Biliary Cirrhosis (PBC) Who Had an Inadequate Response to Ursodeoxycholic Acid
Baseline characteristics by cohort
| Measure |
Open-label: Ustekinumab 90 mg
n=20 Participants
In proof of concept phase of Part 1, participants received ustekinumab 90 milligram (mg) subcutaneously at Week 0, 4 and thereafter every 8 weeks through Week 20. Eligible participants entered long-term extension which began at Week 28 and continued through Week 216.
|
|---|---|
|
Age, Continuous
|
48.8 years
STANDARD_DEVIATION 10.13 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 12Population: Efficacy analysis set included all participants who received at least 1 administration of ustekinumab (full or partial).
The ALP response was defined as a greater than 40 percent (%) decrease from Baseline in ALP concentration at Week 12.
Outcome measures
| Measure |
Open-label: Ustekinumab 90 mg
n=20 Participants
In proof of concept phase of Part 1, participants received ustekinumab 90 milligram (mg) subcutaneously at Week 0, 4 and thereafter every 8 weeks through Week 20. Eligible participants entered long-term extension which began at Week 28 and continued through Week 216.
|
|---|---|
|
Part 1: Number of Participants With Alkaline Phosphatase (ALP) Response at Week 12
|
0 participants
|
SECONDARY outcome
Timeframe: Week 28Population: Efficacy analysis set included all participants who received at least 1 administration of ustekinumab (full or partial).
Outcome measures
| Measure |
Open-label: Ustekinumab 90 mg
n=20 Participants
In proof of concept phase of Part 1, participants received ustekinumab 90 milligram (mg) subcutaneously at Week 0, 4 and thereafter every 8 weeks through Week 20. Eligible participants entered long-term extension which began at Week 28 and continued through Week 216.
|
|---|---|
|
Part 1: Number of Participants With ALP Response at Week 28
|
0 participants
|
SECONDARY outcome
Timeframe: Week 28Population: Efficacy analysis set included all participants who received at least 1 administration of ustekinumab (full or partial).
ALP remission is defined as either normalization of ALP (for participants with baseline ALP between 1.67\*and 2.8\* upper limit of normal \[ULN\] or an ALP less than \[˂\]1.67\*ULN \[for participants with baseline ALP greater than {˃} 2.8\* ULN\]). ALP levels above 1.67\* ULN level were associated with an increased rate of disease progression.
Outcome measures
| Measure |
Open-label: Ustekinumab 90 mg
n=20 Participants
In proof of concept phase of Part 1, participants received ustekinumab 90 milligram (mg) subcutaneously at Week 0, 4 and thereafter every 8 weeks through Week 20. Eligible participants entered long-term extension which began at Week 28 and continued through Week 216.
|
|---|---|
|
Part 1: Number of Participants With ALP Remission at Week 28
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline and Week 28Population: Efficacy analysis set included all participants who received at least 1 administration of ustekinumab (full or partial).
Outcome measures
| Measure |
Open-label: Ustekinumab 90 mg
n=20 Participants
In proof of concept phase of Part 1, participants received ustekinumab 90 milligram (mg) subcutaneously at Week 0, 4 and thereafter every 8 weeks through Week 20. Eligible participants entered long-term extension which began at Week 28 and continued through Week 216.
|
|---|---|
|
Part 1: Percent Change From Baseline in ALP Concentration at Week 28
|
-11.25 percent change
Standard Deviation 17.462
|
SECONDARY outcome
Timeframe: Baseline and Week 28Population: Efficacy analysis set included all participants who received at least 1 administration of ustekinumab (full or partial). "N" (number of participants analyzed) signifies participants who were evalubale for this outcome measure. "n" signifies participants who were evalubale for each specified category.
Outcome measures
| Measure |
Open-label: Ustekinumab 90 mg
n=18 Participants
In proof of concept phase of Part 1, participants received ustekinumab 90 milligram (mg) subcutaneously at Week 0, 4 and thereafter every 8 weeks through Week 20. Eligible participants entered long-term extension which began at Week 28 and continued through Week 216.
|
|---|---|
|
Part 1: Percent Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, and Bilirubin Concentration at Week 28
Alanine Aminotransferase (n=18)
|
-9.21 percent change
Standard Deviation 32.362
|
|
Part 1: Percent Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, and Bilirubin Concentration at Week 28
Aspartate Aminotransferase (n=18)
|
-7.22 percent change
Standard Deviation 27.188
|
|
Part 1: Percent Change From Baseline in Alanine Aminotransferase, Aspartate Aminotransferase, and Bilirubin Concentration at Week 28
Bilirubin (n=3)
|
-4.61 percent change
Standard Deviation 14.183
|
Adverse Events
Open-label: Ustekinumab 90 mg
Serious events: 1 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Open-label: Ustekinumab 90 mg
n=20 participants at risk
In proof of concept phase of Part 1, participants received ustekinumab 90 milligram (mg) subcutaneously at Week 0, 4 and thereafter every 8 weeks through Week 20. Eligible participants entered long-term extension which began at Week 28 and continued through Week 216.
|
|---|---|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
Other adverse events
| Measure |
Open-label: Ustekinumab 90 mg
n=20 participants at risk
In proof of concept phase of Part 1, participants received ustekinumab 90 milligram (mg) subcutaneously at Week 0, 4 and thereafter every 8 weeks through Week 20. Eligible participants entered long-term extension which began at Week 28 and continued through Week 216.
|
|---|---|
|
General disorders
Fatigue
|
40.0%
8/20 • Week 0 up to final safety visit in Part 1
|
|
General disorders
Feeling abnormal
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
General disorders
Injection site bruising
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
General disorders
Injection site erythema
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
General disorders
Pyrexia
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Infections and infestations
Urinary tract infection
|
20.0%
4/20 • Week 0 up to final safety visit in Part 1
|
|
Infections and infestations
Influenza
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Infections and infestations
Oral herpes
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Infections and infestations
Sinusitis
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Infections and infestations
Upper respiratory tract infection
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Infections and infestations
Bronchitis
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Infections and infestations
Ear infection
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Infections and infestations
Vaginal infection
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Nausea
|
15.0%
3/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Abdominal pain
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Dyspepsia
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Inguinal hernia
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Paraesthesia oral
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Salivary gland enlargement
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Gastrointestinal disorders
Toothache
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Nervous system disorders
Headache
|
25.0%
5/20 • Week 0 up to final safety visit in Part 1
|
|
Nervous system disorders
Migraine
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Nervous system disorders
Paraesthesia
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Nervous system disorders
Radiculopathy
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.0%
3/20 • Week 0 up to final safety visit in Part 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Reproductive system and breast disorders
Menorrhagia
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Reproductive system and breast disorders
Vulvovaginal dryness
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Reproductive system and breast disorders
Vulvovaginal pruritus
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.0%
2/20 • Week 0 up to final safety visit in Part 1
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Respiratory, thoracic and mediastinal disorders
Allergic sinusitis
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Eye disorders
Conjunctivitis
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Eye disorders
Dry eye
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Injury, poisoning and procedural complications
Laceration
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Injury, poisoning and procedural complications
Rib fracture
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Blood and lymphatic system disorders
Anaemia
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Hepatobiliary disorders
Hepatic pain
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Immune system disorders
Seasonal allergy
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Investigations
Weight decreased
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Psychiatric disorders
Insomnia
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Renal and urinary disorders
Dysuria
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Vascular disorders
Raynaud's phenomenon
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.0%
1/20 • Week 0 up to final safety visit in Part 1
|
Additional Information
Senior Director, Clinical Development, Immunology
Janssen, R&D, LLC, Spring House, PA
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60