The primary hypothesis of this study is that a dose-response relationship exists between disease activity as measured by the change from baseline in the Mayo score at Week 8 and JNJ-54781532 treatment regimens in subjects with moderately to severely…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy evaluations will include:
* Mayo score and partial Mayo score
* Inflammatory Bowel Disease Questionnaire (IBDQ)
* C-reactive protein (CRP)
* Fecal lactoferrin and fecal calprotectin
* Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
Primary Endpoint
The primary endpoint is the change from baseline in the Mayo score at Week 8.
Secondary outcome
The secondary objectives are as follows:
1. To evaluate the efficacy of JNJ-54781532 in inducing clinical response at
Week 8.
2. To evaluate the efficacy of JNJ-54781532 in inducing clinical remission at
Week 8.
3. To evaluate the efficacy of JNJ-54781532 in inducing mucosal healing at Week
8.
Exploratory Objectives
The exploratory objectives are as follows:
1. To explore the optimal treatment duration of JNJ-54781532 for the primary
and major secondary endpoints.
2. To explore the response to treatment through Week 32 among subjects who are
in clinical response to JNJ-54781532 at Week 8.
3. To explore the efficacy of JNJ-54781532 in achieving partial Mayo score
response (or partial Mayo score remission) and eliminating corticosteroid use
at Week 32 among subjects who are in clinical response and receiving
concomitant corticosteroids at Week 8.
Background summary
JNJ-54781532, also known as JNJ-54781532-AAD and ASP015K, is an investigational
oral immunosuppressant that acts by inhibiting Janus kinase (JAK), with
moderate selectivity for JAK3, a key enzyme in the interleukin (IL)-2 signal
pathway. ASP015K is being developed by Astellas Pharma
Global Development, Inc. (Astellas) and has been studied in subjects with
moderate to severe chronic plaque psoriasis, and for the prophylaxis of solid
organ rejection in subjects receiving allogeneic kidney or liver transplants.
ASP015K is currently being studied in subjects with rheumatoid arthritis (RA).
The sponsor has entered into a codevelopment agreement with Astellas, and under
this agreement the sponsor has acquired the rights to pursue the development of
this compound for any additional indications. As such, the sponsor is currently
developing JNJ-54781532 (ASP015K) for the treatment of subjects with moderately
to severely active ulcerative colitis (UC).
Study objective
The primary hypothesis of this study is that a dose-response relationship
exists between disease activity as measured by the change from baseline in the
Mayo score at Week 8 and JNJ-54781532 treatment regimens in subjects with
moderately to severely active UC.
Study design
This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled,
parallel-group, dose-response study of oral tablets of JNJ-54781532 in adult
subjects with moderately to severely active UC, defined as a baseline Mayo
score of 6 to 12, with an endoscopic subscore of *2. Eligible subjects will be
randomized to 1 of 5 treatment groups (ie, 4 different dosages of JNJ-54781532
or placebo) at Week 0. At Week 8, subjects who are randomized to placebo and
not in clinical response will receive treatment with JNJ-54781532 150 mg once
daily; all the other subjects will continue to receive their original
randomized dosage of study agent through Week 32. All subjects will have a
final safety visit approximately 4 weeks after their last dose of study agent.
The end of the study is defined as the date the last subject completes the
final safety visit (ie, approximately 4 weeks after the last dose of study
agent).
Eligible subjects will be randomized in a 1:1:1:1:1 ratio to 1 of 5 treatment
groups at Week 0:
* Placebo
* JNJ-54781532 25 mg once daily
* JNJ-54781532 75 mg once daily
* JNJ-54781532 150 mg once daily
* JNJ-54781532 75 mg twice daily
All subjects will receive their original randomized dosage of study agent
through Week 8 and will be assessed for clinical response (ie, a decrease from
baseline in the Mayo score by *30% and *3 points, with either a decrease from
baseline in the rectal bleeding subscore of *1 or a rectal bleeding subscore of
0 or 1) at that timepoint. Treatment after Week 8 will be determined by
clinical response status as follows:
* Subjects in clinical response at Week 8: These subjects will continue to
receive their original randomized dosage of study agent through Week 32.
* Subjects not in clinical response at Week 8:
* Subjects randomized to placebo will begin treatment with JNJ-54781532 150 mg
once daily.
* Subjects randomized to JNJ-54781532 will continue to receive their original
randomized dosage of JNJ-54781532.
* At Week 16, subjects who do not achieve a partial Mayo score response (ie, a
change from baseline of *3 in the partial Mayo score) at Week 16 will be
discontinued from study agent. Subjects who achieve a partial Mayo score
response at Week 16 can continue receiving
JNJ-54781532 through Week 32. To maintain the blind, subjects randomized to a
once daily dosage of JNJ-54781532 will receive a second daily administration of
placebo. Study agent will be administered orally as 5 tablets (ie, all active
drug, all matching placebo, or mixed active drug and matching placebo) given
twice daily according to treatment group assignment. Study agent should be
taken with food and approximately 240 mL (8 oz) of water. Study agent should be
taken at approximately the same time each day.
Intervention
There are 5 Treatment groups in this study. Four of the treatment groups
include different doses of JNJ-54781532. One of the treatment groups is
treatment with placebo.
The treatment groups for this study are:
*JNJ-54781532 25 mg once daily
* JNJ-54781532 75 mg once daily
* JNJ-54781532 150 mg once daily
* JNJ-54781532 75 mg twice daily
* Placebo
The chance that the subject will be placed in any one of these groups is 1 out
of 5.
Study burden and risks
Number of visits:12x
Clinical laboratory assessments: 12x
PK samples at week 2: pre-dose, 0.5, 1 and 3 hour post-dose
Physical examination: 4x
ECG: 2x
X-ray:1x
Endoscopy: 2x (with biopsy)
Questionnaires:2x Inflammatory bowel disease questionnaire.
Diary: daily Mayo diary card + medication diary
Side effects:
Antwerpseweg 15-17
Beerse 2340
BE
Antwerpseweg 15-17
Beerse 2340
BE
Listed location countries
Age
Inclusion criteria
- Have a clinical diagnosis of ulcerative colitis (UC) at least 3 months prior to screening ;- Have moderately to severely active UC, defined as a baseline (Week 0) Mayo score of 6 to 12 ; including an endoscopy subscore greater than or equal to 2 as determined by a central read of the video endoscopy ;- Current treatment with oral corticosteroids or have a history of failure to respond to, or tolerate, at least 1 of the following therapies oral corticosteroids (including budesonide), 6-mercaptopurine (6-MP), azathioprine (AZA), or anti-tumor necrosis factor therapy or be corticosteroid dependent (ie, an inability to successfully taper corticosteroids without a return of the symptoms of UC ;- Must discontinue 6-MP/AZA for at least 1 week before the first dose of study medication
Exclusion criteria
- At imminent risk for colectomy ;- Have ulcerative colitis limited to the rectum only or to less than 20 centimeter of the colon ;- Presence of a stoma ;- Presence or history of a fistula ;- History or current diagnosis of active or latent tuberculosis (An exception is made for
subjects who have a history of latent TB and are currently receiving treatment for latent
TB) , human immunodeficiency virus, hepatitis C virus or hepatitis B virus infection ;- Have had more than 1 herpes zoster infection or have had any diagnosis disseminated herpes zoster;- Previous treatment with a janus kinase inhibitor (eg, tofacitinib)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-000263-88-NL |
| CCMO | NL46443.018.13 |