A Safety Extension Study of Ontamalimab in Participants With Moderate to Severe Ulcerative Colitis or Crohn's Disease (AIDA)

A Phase 3 Long-term Safety Extension Study of SHP647 in Subjects With Moderate to Severe Ulcerative Colitis or Crohn's Disease (AIDA)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03283085

Enrollment

557

Registered

2017-09-14

Start date

2018-02-27

Completion date

2023-12-13

Last updated

2024-06-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Crohn's Disease, Ulcerative Colitis

Keywords

Immunosuppressants, Mesalamine, Ulcerative Colitis, Crohn's disease, Gastroenteritis

Brief summary

The purpose of this study is to evaluate the safety and tolerability of long-term treatment with ontamalimab in participants with moderate to severe Ulcerative Colitis (UC) or Crohn's disease (CD)

Interventions

DRUG25 mg Ontamalimab

Ontamalimab SC solution for injection

DRUG75 mg Ontamalimab

Ontamalimab SC solution for injection

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

16 Years to 80 Years

Healthy volunteers

Inclusion criteria

Participants with Ulcerative Colitis (UC): * Participants and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions. * Participants must be able to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent and/or assent, as applicable, to participate in the study. * Participants must have been enrolled previously in study SHP647-301 (NCT03259334), SHP647-302 (NCT03259308), and are in the treatment period of Study SHP647-303, completed the early termination (ET) or Week 52 visit in maintenance study SHP647-303 (NCT03290781), had responded to ontamalimab treatment (in the induction and/or maintenance studies), and meet one of the following criteria: a. Participants are on placebo at the maintenance study ET or Week 52 visit: they received ontamalimab in the induction studies and fulfilled the maintenance study response criteria, OR b. Participants have received ontamalimab at the maintenance study ET or Week 52 visit: i) Clinical composite score that has decreased by \>or=2 points and \>or=30%, with an accompanying decrease in the subscore for RB \>or=1 point or a subscore for RB \<or=1, compared to the baseline value for induction studies, and/or ii) Composite score that has decreased by \>or=30% and \>or=3 points compared to the baseline value for induction studies. * Participants receiving any treatment(s) for UC are eligible provided they have been on a stable dose for the designated period of time. Participants with Crohn's Disease: * Participants and/or their parent or legally authorized representative must have an understanding, ability, and willingness to fully comply with study procedures and restrictions. * Participants must be able to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent and/or assent, as applicable, to participate in the study. * Participants must have been enrolled previously in Study SHP647-305 (NCT03559517) or SHP647-306 (NCT03566823) and are in the treament period of Study SHP647-307 (NCT03627091), completed the ET or Week 52 visit in maintenance study SHP647-307, had responded to ontamalimab treatment (in the induction or maintenance studies) and meet one of the following criteria: 1. Participants are on placebo at the maintenance study ET or Week 52 visit: they received ontamalimab in the induction study and fulfilled the maintenance study response criteria, OR 2. Participants have received ontamalimab at the maintenance study ET or Week 52 visit: i) CDAI score that has decreased by \>or=100 points at EOT visit compared to the baseline value for induction studies, and/or ii) SES-CD that has decreased by \>or=25% compared to the baseline value for induction studies. * Participants receiving any treatment(s) for CD are eligible provided they have been on a stable dose for the designated period of time.

Exclusion criteria

Participants with UC: * Participants who had major protocol deviation(s) (as determined by the sponsor) in study SHP647-301, SHP647-302, or SHP647-303. * Participants who permanently discontinued investigational product because of an AE, regardless of relatedness to investigational product, in study SHP647-301, SHP647-302, or SHP647-303. * Participants who are likely to require major surgery for UC. * Participants are females who became pregnant during study SHP647-301, SHP647-302, or SHP647-303, females who are lactating, females who are planning to become pregnant during the study period, or males or females of childbearing potential not agreeing to continue using appropriate contraception methods (i.e. highly effective methods for female and medically appropriate methods for male study participants) through the conclusion of study participation. * Participants who do not agree to postpone donation of any organ or tissue, including male participants who are planning to bank or donate sperm and female participants who are planning to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of investigational product. * Participants who, in the opinion of the investigator or the sponsor, will be uncooperative or unable to comply with study procedures. * Participants who have a newly-diagnosed malignancy or recurrence of malignancy (other than resected cutaneous basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ of the uterine cervix that has been treated with no evidence of recurrence). * Participants who have developed any major illness/condition or evidence of an unstable clinical condition (example \[e.g.\], renal, hepatic, hematologic, gastrointestinal \[except disease under study\], endocrine, cardiovascular, pulmonary, immunologic \[e.g. Felty's syndrome\], or local active infection/infectious illness) that, in the investigator's judgment, will substantially increase the risk to the participant if he or she participates in the study. * Participants with any other severe acute or chronic medical or psychiatric condition or laboratory or ECG abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. * Participants with known exposure to Mycobacterium tuberculosis (TB) since testing at screening in study SHP647-301 (NCT03259334) or SHP647-302 (NCT03259308) and who have been advised to require treatment for latent or active disease, but who are without a generally accepted course of treatment. * Participants who are investigational site staff members or relatives of those site staff members or participants who are sponsor employees directly involved in the conduct of the study. * Participants who are participating in other investigational studies (other than SHP647-301, SHP647-302, or SHP647-303) or plan to participate in other investigational studies during long-term extension study SHP647-304. Participants with Crohn's Disease: * Participants who had major protocol deviation(s) (as determined by the sponsor) in study SHP647-305, SHP647-306 or SHP647-307. * Participants who permanently discontinued investigational product because of an adverse events (AE), regardless of relatedness to investigational product, in study SHP647-305, SHP647-306 or SHP647-307. * Participants who are likely to require major surgery for CD or developed acute severe complications of CD (with or without fulfilling the treatment failure criteria in the maintenance study) that required immediate intervention (e.g. need for immediate biologic treatment with proven effect) and/or Crohn's Disease Activity Index (CDAI) score more than (\>) 450. * Participants are females who became pregnant during study SHP647-305, SHP647-306 or SHP647-307, females who are lactating, females who are planning to become pregnant during the study period, or males or females of childbearing potential not agreeing to continue appropriate contraception methods (i.e. highly effective methods for female and medically appropriate methods for male study participants) through the conclusion of study participation. * Participants who do not agree to postpone donation of any organ or tissue, including male participants who are planning to bank or donate sperm and female participants who are planning to harvest or donate eggs, for the duration of the study and through 16 weeks after last dose of investigational product.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Serious Infections	From first dose of study drug up to EOS (up to 5.79 years)	Serious infections were defined as any infections that were life-threatening or those requiring hospitalization or intravenous antibiotics based on the investigator's assessment.
Number of Participants With Discernible Changes in Electrocardiogram (ECG) Over Time	From first dose of study drug up to EOS (up to 5.79 years)	ECG included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals parameters measurement. Any discernible changes in the ECG value over time based on investigator interpretation were reported.
Number of Participants With Discernible Changes in Vital Signs Over Time	From first dose of study drug up to EOS (up to 5.79 years)	Vital sign assessments included blood pressure, pulse, respiratory rate, and temperature. Any discernible changes in vital signs over time per investigator interpretation were reported.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	From first dose of study drug up to end of study [EOS] (up to 5.79 years)	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs (TEAEs) were defined as AEs with start dates or worsening dates at the time of or following the first exposure to investigational product.
Number of Participants With Notable Changes in Clinical Laboratory Parameters Over Time	From first dose of study drug up to EOS (up to 5.79 years)	Clinical laboratory assessments included hematology, serum chemistry and urinalysis. Any notable changes in the clinical laboratory value over time based on the investigator interpretation were reported.

Secondary

Measure	Time frame	Description
Number of Participants With Crohn's Disease With Treatment Response Over Time	Up to 5.79 years	Treatment response over time=Crohn's Disease Activity Index(CDAI)score that has decreased ≥100 points and/or simple endoscopic score for Crohn's disease(SES-CD)that has decreased by ≥25%,both compared to baseline value for induction studies.SES-CD is simple scoring system with 4 endoscopic variables measured in same 5 ileocolonic segments as CD index of severity. Overall values on SES-CD range from 0-56,higher values=more severe disease.4 endoscopic variables are scored from 0-3 in each bowel segment:ileum,right/transverse/left colon,rectum. Presence & size of ulcers(none=0;diameter 0.1-0.5centimeter(cm)=1;0.5-2cm=2;\>2cm=3);extent of ulcerated surface(none=0;\<10%=1;10%-30%=2; \>30%= 3);extent of affected surface(none=0;\<50%=1;50%-75%=2;\>75%=3);Presence & type of narrowing (none=0;single can be passed=1;multiple can be passed=2;cannot be passed=3).
Number of Participants With Ulcerative Colitis With Treatment Response Over Time	Up to 5.79 years	Treatment response over time was defined as clinical composite score that has decreased by greater than or equal to (≥2) points and ≥30 percentage (%), with an accompanying decrease in the sub score for rectal bleeding (RB) ≥1 point or a subscore for RB ≤ 1, and/or composite score that has decreased by ≥30% and ≥3 points compared to the baseline value for induction studies. The clinical composite score is a measure consisting of sub scores RB (0-3) plus stool frequency (0-3) with higher scores indicating more severe disease. With the implementation of amendment 4 of the protocol the study became a single arm study with all participants receiving the 75 mg dose of ontamalimab. Hence, only those UC participants who were receiving the 75 mg dose of ontamalimab every 4 weeks and participating in amendment 4 of the protocol were analyzed in this outcome measure.

Countries

Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Colombia, Croatia, Czechia, Estonia, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Lebanon, Lithuania, Mexico, Netherlands, New Zealand, Poland, Portugal, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom, United States

Participant flow

Recruitment details

Participants took part in the study at 225 investigative sites in 33 countries from 27 February 2018 to 13 December 2023.

Pre-assignment details

Participants from induction and maintenance studies of ulcerative colitis (UC) \[SHP647-301 (NCT03259334), SHP647-302 (NCT03259308), and SHP647-303 (NCT03290781)\] and Crohn's disease (CD) \[SHP647-305 (NCT03559517), SHP647-306 (NCT03566823), and SHP647-307 (NCT03627091)\] were enrolled to receive either 25 milligrams (mg) or 75 mg ontamalimab.

Participants by arm

Arm	Count
UC: Ontamalimab 25 mg Participants received 25 milligrams (mg) of ontamalimab solution for injection subcutaneously (SC), every 4 weeks (Q4W), for up to 3 years.	89
UC: Ontamalimab 25 mg Then 75 mg Participants received 25 mg of ontamalimab solution for injection SC, Q4W, and later progressed to receive 75 mg in a similar manner for up to 5.79 years.	159
UC: Ontamalimab 75 mg Participants received 75 mg of ontamalimab solution for injection SC, Q4W, for up to 5.79 years.	268
CD: Ontamalimab 25 mg Participants received 25 mg of ontamalimab solution for injection SC, Q4W, for up to 3 years.	5
CD: Ontamalimab 25 mg Then 75 mg Participants received 25 mg of ontamalimab solution for injection SC, Q4W, and later progressed to receive 75 mg in a similar manner for up to 5.79 years.	10
CD: Ontamalimab 75 mg Participants received 75 mg of ontamalimab solution for injection SC, Q4W, for up to 5.79 years.	26
Total	557

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Adverse Event	18	3	13	0	0	5
Overall Study	Death	0	0	3	1	0	0
Overall Study	Lack of Efficacy	12	6	24	1	1	0
Overall Study	Lost to Follow-up	2	0	2	0	0	1
Overall Study	Physician Decision	14	8	19	0	0	2
Overall Study	Pregnancy	0	0	1	0	0	0
Overall Study	Reason not Specified	0	4	8	0	0	1
Overall Study	Site Terminated by Sponsor	1	0	3	0	0	0
Overall Study	Withdrawal by Subject	42	21	66	3	3	5

Baseline characteristics

Characteristic	UC: Ontamalimab 25 mg	UC: Ontamalimab 25 mg Then 75 mg	UC: Ontamalimab 75 mg	CD: Ontamalimab 25 mg	CD: Ontamalimab 25 mg Then 75 mg	CD: Ontamalimab 75 mg	Total
Age, Categorical <=18 years	0 Participants	2 Participants	7 Participants	0 Participants	1 Participants	1 Participants	11 Participants
Age, Categorical >=65 years	2 Participants	9 Participants	22 Participants	1 Participants	0 Participants	0 Participants	34 Participants
Age, Categorical Between 18 and 65 years	87 Participants	148 Participants	239 Participants	4 Participants	9 Participants	25 Participants	512 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	12 Participants	15 Participants	0 Participants	1 Participants	2 Participants	35 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	84 Participants	146 Participants	251 Participants	5 Participants	9 Participants	24 Participants	519 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	3 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	2 Participants	4 Participants	0 Participants	0 Participants	1 Participants	7 Participants
Race (NIH/OMB) Asian	7 Participants	14 Participants	24 Participants	1 Participants	0 Participants	0 Participants	46 Participants
Race (NIH/OMB) Black or African American	0 Participants	2 Participants	4 Participants	0 Participants	0 Participants	2 Participants	8 Participants
Race (NIH/OMB) More than one race	2 Participants	2 Participants	3 Participants	0 Participants	0 Participants	0 Participants	7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	4 Participants	2 Participants	0 Participants	1 Participants	0 Participants	9 Participants
Race (NIH/OMB) White	77 Participants	135 Participants	231 Participants	4 Participants	9 Participants	23 Participants	479 Participants
Sex: Female, Male Female	29 Participants	67 Participants	111 Participants	1 Participants	5 Participants	14 Participants	227 Participants
Sex: Female, Male Male	60 Participants	92 Participants	157 Participants	4 Participants	5 Participants	12 Participants	330 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	0 / 89	0 / 159	3 / 268	1 / 5	0 / 10	0 / 26
other Total, other adverse events	47 / 89	109 / 159	155 / 268	3 / 5	8 / 10	14 / 26
serious Total, serious adverse events	15 / 89	21 / 159	46 / 268	2 / 5	2 / 10	4 / 26

Outcome results

Primary

Number of Participants With Discernible Changes in Electrocardiogram (ECG) Over Time

ECG included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals parameters measurement. Any discernible changes in the ECG value over time based on investigator interpretation were reported.

Time frame: From first dose of study drug up to EOS (up to 5.79 years)