This study has been transitioned to CTIS with ID 2023-506046-24-00 check the CTIS register for the current data. Main:To evaluate the long-term safety and tolerability of efavaleukin alfa in subjects with moderate to severe ulcerative colitis (UC)…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Treatment-emergent adverse events
Secondary outcome
- Clinical response at week 52 and 104
- Clinical remission at week 52 and 104
- Durable clinical remission at week 52 and 104
- Endoscopic remission at week 52 and 104
- Histologic remission at week 52 and 104
- Corticosteroid-free remission at week 52 and 104 in subjects receiving
corticosteroids at randomization of Study 20170104
- Combined endoscopic and histologic remission at week 52 and 104
- Symptomatic remission at week 52 and 104
- Change from baseline of Study 20170104 in histological score (Geboes) at week
52 and 104
Background summary
Ulcerative colitis is a chronic inflammatory bowel disease (IBD) with symptoms
of abdominal pain, bloody diarrhea, and fecal urgency, which can occur without
warning, placing a significantburden on daily life. There is an increased risk
of colorectal cancer, with risk factors such as long duration of disease,
extensive colonic involvement, severe inflammation and epithelialdysplasia, and
childhood-onset disease.
Conventional treatment consists of oral or topical aminosalicylates (5-ASAs) or
topical steroids for induction of remission and oral and/or topical 5-ASAs for
maintenance (Rubin et al 2019).Advanced therapies for treatment include
immunosuppressants, biologic therapies such as anti-TNF inhibitors,
anti-integrins (ie, vedolizumab), and interleukin-12 and -23 antagonists
(ie,ustekinumab) as well as small molecule JAK inhibitors (eg, tofacitinib).
Despite this there is a lack of effective treatment, with patients becoming
intolerant or nonresponsive with a proportionof patients being unsuitable for
treatment. Therefore, there continues to be unmet need for new therapies with
better safety and efficacy, particularly for achieving long term,
steroid-free,remission and mucosal healing.
A loss of homeostatic balance between Treg and other lymphocytes is considered
a causative factor in many inflammatory conditions, with ulcerative colitis
associated with geneticpolymorphisms in the IL-2 gene. Efavaleukin alfa is an
IL-2 mutein Fc fusion protein that has been developed to preferentially expand
Tregs in patients with inflammatory diseases. Thisgreater selectivity of
efavaleukin alfa may provide for greater efficacy and a wider therapeutic
margin in inflammatory diseases relative to low dose recombinant IL-2 based
modalities and,therefore,
supports the investigation of efavaleukin alfa for the treatment of UC with
lower side effects.
This study is a phase 2 LTE study for subjects who completed the 52 week phase
2 dose-finding study (Study 20170104). Subjects will enroll into the LTE in a
blinded manner on the same dose they were receiving at the completion of their
participation in Study 20170104. This study will evaluate the long-term safety
and clinical efficacy of efavaleukin alfa in subjects entering Study 20170104
with moderately to severely active UC.
Study objective
This study has been transitioned to CTIS with ID 2023-506046-24-00 check the CTIS register for the current data.
Main:
To evaluate the long-term safety and tolerability of efavaleukin alfa in
subjects with moderate to severe ulcerative colitis (UC)
Secondary:
- To evaluate the effect of efavaleukin alfa long-term treatment on clinical
response
- To evaluate the effect of efavaleukin alfa long-term treatment on clinical
remission
- To evaluate the effect of efavaleukin alfa long-term treatment on durable
clinical remission
- To evaluate the effect of efavaleukin alfa long-term treatment on endoscopic
remission
- To evaluate the effect of efavaleukin alfa long-term treatment on histologic
remission
- To evaluate the effect of efavaleukin alfa long-term treatment on
corticosteroid-free remission - To evaluate the effect of efavaleukin alfa
long-term treatment on combined endoscopic and histologic remission
- To evaluate the effect of efavaleukin alfa long-term treatment on symptomatic
remission
- To evaluate the effect of efavaleukin alfa long-term treatment on change in
histological score
Study design
This phase 2 long-term extension (LTE) study will assess the long-term safety
and efficacy of efavaleukin alfa in subjects with moderately to severely active
ulcerative colitis (UC). Efavaleukin alfa may be a viable treatment option for
patients with moderately to severely active UC who have failed at least one of
the following: conventional therapy (eg, immunomodulators, corticosteroids),
biologic therapy, or targeted small molecule therapy (ie, Janus kinase [JAK]
inhibitor).
This study is a phase 2 LTE study for subjects who completed the 52 week phase
2 dose-finding study (Study 20170104). Subjects will enroll into the LTE in a
blinded manner on the same dose they were receiving at the completion of their
participation in Study 20170104. This study will evaluate the long-term safety
and clinical efficacy of efavaleukin alfa in subjects entering Study 20170104
with moderately to severely active UC.
Intervention
Subjects will enroll into the LTE in a blinded manner on the same dose they
were receiving at the completion of their participation in study 20170104.
Study burden and risks
See responses to questions E2 / E4 / E6 / E9 and E9a.
The safety of efavaleukin alfa has been evaluated in healthy subjects and in
subjects with rheumatoid arthritis (RA), chronic graft versus host
disease(cGvHD), and systemic lupus erythematosus (SLE). See Section 2.3 of the
protocol for more information on these studies. Efavaleukin alfa has been well
tolerated in clinical studies and has an acceptable safety profile. Based upon
the totality of available safety data to date, the benefit/risk profile of
efavaleukin alfa is favorable. The benefit risk assessment detailed in Section
2.3 supports the conduct of this phase 2 clinical trial in subjects with UC.
Reference should be made to the latest version of the Investigator*s Brochure
for further safety data on efavaleukin alfa.
Minervum 7061
Breda 4817 ZK
NL
Minervum 7061
Breda 4817 ZK
NL
Listed location countries
Age
Inclusion criteria
101 Subject has provided informed consent prior to initiation of any study
specific activities/procedures.
102 Subject has completed the week 52 endoscopy in the phase 2 parent
dose-finding study (20170104) and who in the opinion of the investigator may
benefit from continued treatment.
Exclusion criteria
201 Permanent discontinuation of investigational product during the 52-week
phase 2 dose finding study (20170104) for any reason. Disease Related
202 Adenoma and dysplasia exclusion criteria:
o Any current sporadic adenoma without dysplasia (adenomatous polyps
occurring proximal to known areas of colitis) that has not been removed.
o Dysplasia occurring in flat mucosa, sporadic adenomas containing
dysplasia, and dysplasia-associated lesions or masses will be managed as
follows:
* 1. Any history or current evidence of high-grade dysplasia.
* 2. Any history or current evidence of dysplasia occurring in flat
mucosa. This includes histopathology reporting indefinite for dysplasia,
low-grade dysplasia, and high-grade dysplasia.
* 3. Any history or current evidence of a nonadenoma like dysplasia
associated lesions or masses, with or without evidence of
dysplasia.
* 4. Any current sporadic adenoma containing dysplasia or any current
adenoma-like dysplasia-associated lesions or masses that has not been removed.
Other Medical Conditions
203 Any malignancy diagnosed during Study 20170104, including evidence of
cutaneous basal or squamous cell carcinoma or melanoma
204 Active infection (including chronic, acute, recurrent, opportunistic
infections) at the time of eligibility evaluation requiring intravenous
(IV)anti-infectives or hospitalization (infections requiring oral and/or
topicalanti-infective[s] for > 7 days may be allowed in consultation with the
Amgen physician).
205 Required systemic corticosteroid use for any indication other than UC. The
only exception is corticosteroids used for the treatment of adrenal
insufficiency are allowed. Prior/Concomitant Therapy
206 Plan to receive a live (attenuated) vaccine during the treatment period and
up to 6 weeks after the last dose of investigational product inthe LTE study.
Prior/Concurrent Clinical Study Experience
207 Currently receiving treatment in another investigational device or drug
study. Other investigational procedures while participating in this study are
excluded.
Other Exclusions
208 Female subjects who are pregnant or breastfeeding or planning to become
pregnant or breastfeed during study and for an additional 6 weeks after the
last dose of investigational product.
209 Female subjects of childbearing potential unwilling to use protocol
specified method of contraception see Appendix 5 (Section 11.5) during
treatment and for an additional 6 weeks after the last dose of investigational
product.
210 Subject has known sensitivity to any of the products to be administered
during dosing with the exception of subjects who exhibitedsensitivity in Study
20170104 but did not result in treatment discontinuation.
211 Subject likely to not be available to complete all protocol-required study
visits or procedures, and/or to comply with all required study procedures
(e.g., Clinical Outcome Assessments) to the best of the subject and
investigator's knowledge.
212 Subject has a history or evidence of any other clinically significant
disorder (including laboratory abnormalities), condition, or disease that, in
the opinion of the investigator or Amgen physician, if consulted would pose a
risk to subject safety, or interfere with the study evaluation, procedures, or
completion.
214 Female subjects of reproductive potential must agree not to donate eggs
during the study and for 6 weeks after receiving the last dose of
investigational product.
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 |
|---|---|
| EU-CTR | CTIS2023-506046-24-00 |
| EudraCT | EUCTR2022-001686-12-NL |
| ClinicalTrials.gov | NCT-nummernognietbekend.hetnummervolgt |
| CCMO | NL82759.028.22 |