CTRI/2025/02/080762 [Registered on: 18/02/2025] Trial Registered Prospectively
Last Modified On:
06/03/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Study of AVT16 and Entyvio® in Male and Female Subjects Aged 18 to 80 Years Inclusive With Moderate to Severe Active Ulcerative Colitis
Scientific Title of Study
A Parallel-Group Treatment, Double-Blind, 2-Arm Study to Investigate the Comparative Efficacy, Safety, and Immunogenicity Between Intravenous AVT16 and Entyvio® in Male and Female Subjects Aged 18 to 80 Years Inclusive With Moderate to Severe Active Ulcerative Colitis
Trial Acronym
PYRAMID
Secondary IDs if Any
Secondary ID
Identifier
2023-507705-34-00
EudraCT
AVT16-GL-C01 Protocol Version 3.0(Amendment 2.0), 02Feb2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Rashmi Chitgupi
Designation
Country Head- Clinical Management
Affiliation
PPD Pharmaceutical Development India Private Limited
Address
102-A Wing Fulcrum, Hiranandani Business Park, Sahar Road,
Andheri East 101-A Wing Fulcrum, Hiranandani Business Park,
Sahar Road, Andheri East
Mumbai MAHARASHTRA 400099 India
Phone
02266022900
Fax
Email
rashmi.chitgupi@ppd.com
Details of Contact Person Scientific Query
Name
Rashmi Chitgupi
Designation
Country Head- Clinical Management
Affiliation
PPD Pharmaceutical Development India Private Limited
Address
102-A Wing Fulcrum, Hiranandani Business Park, Sahar Road,
Andheri East 101-A Wing Fulcrum, Hiranandani Business Park,
Sahar Road, Andheri East
Mumbai MAHARASHTRA 400099 India
Phone
02266022900
Fax
Email
rashmi.chitgupi@ppd.com
Details of Contact Person Public Query
Name
Rashmi Chitgupi
Designation
Country Head- Clinical Management
Affiliation
PPD Pharmaceutical Development India Private Limited
Address
102-A Wing Fulcrum, Hiranandani Business Park, Sahar Road,
Andheri East 101-A Wing Fulcrum, Hiranandani Business Park,
Sahar Road, Andheri East
102, A Wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri East, Mumbai (India) – 400099
Countries of Recruitment
Argentina Bosnia and Herzegovina Bulgaria Colombia Croatia Czech Republic Georgia Hungary India Italy Latvia Mexico Peru Poland Romania Serbia Slovakia Spain Sri Lanka Ukraine
Clinical Research Department, Beside Psychiatric Department, Ward No 3, Sawangi- Meghe, 442004 Wardha MAHARASHTRA
7768901370
drvijendrakirnake@gmail.com
Dr Rupa Banerjee
AIG Hospital, Asian Institute of Gastroenterology
Tower A, 6th Floor, IBD Centre, Survey No 136, 4/5, Plot No 2/3, Mindspace Road, P Janardhan Reddy Nagar, Gachibowli, Hyderabad-500032 Telangana, India Hyderabad TELANGANA
9849287530
rupabanerjee.aig@gmail.com
Dr Bhabadev Goswami
Dispur Hospital Private Limited
Gastro Department, Ground Floor, Room Number 1, Institute of Digestive and Liver Diseases, Ganeshguri Kamrup ASSAM
03612232962
bhabadev@rediffmail.com
Dr Mukul Rastogi
Fortis Hospital Noida
Room number 2142, Research Department, First Floor OPD, B- 22, Sector-62 Noida- 201301 Gautam Buddha Nagar UTTAR PRADESH
9312756727
mukulrajul@rediffmail.com
Dr Ravindra Gaadhe
Gastroplus Hospital
Galaxy Bazaar Complex, 2nd & 3rd floor, D Block, (Linking Himalaya mall to Vastrapur Lake, Sunrise Park Road, Vastrapur, Ahmedabad- 380054 Ahmadabad GUJARAT
9276558517
ravindragaadhe@gmail.com
Dr Krishnadas Devadas
Government Medical College
Department of Medical Gastroenterology, Superspeciality block, Ground Floor, Medical College PO, 695011 Thiruvananthapuram KERALA
9847111824
kdas40@gmail.com
Dr Vinay Kumar
GSVM Medical College
Department of Medicine, Ground Floor, Room Number 20 and 21, Swaroop Nagar, 208002 Kanpur Nagar UTTAR PRADESH
8004877113
Drvinaykumar011@gmail.com
Dr Saumin P Shah
Gujarat Gastro and Vascular Hospital
Basement, OPD, Clinical Research Department, Opposite Shree Ram Petrol Pump, Anand Mahal Road, Adajan, 395009 Surat GUJARAT
9408042224
dr.sauminpshah@gmail.com
Dr Manish Bhatnagar
ICON Hospital
Research Department, Basement, Beside Kalyan Pushti Haveli, Opposite Alpha One (Ahmedabad One) Mall Exit, Near Vastrapur Lake, Vastrapur
380015 Ahmadabad GUJARAT
7926303312
bhatnagarclinic@yahoo.com
Dr Saket Kumar
Indira Gandhi Institute of Medical Sciences
Department of Gastrosurgery, Third Floor, Room number 172, Sheikhpura, 800014 Patna BIHAR
9621502507
drsaketigims@gmail.com
Dr Santosh Hajare
KLES Dr Prabhakar Kore Hospital and Medical Research Centre
OPD No 32, Department gastroentrology ,2nd Floor, Nehrunagar, Belagavi - 590010 Belgaum KARNATAKA
8312470400
drsantoshhajare@gmail.com
Dr Sanjay Chandnani
Lokmanya Tilak Municipal Medical College and General Hospital
Department of Gastroenterology,Room No. 446, 4th Floor, Sion West- 400022 Mumbai MAHARASHTRA
919049708800
sanjy.med@gmail.com
Dr Premashis Kar
Max Super Speciality Hospital
Department of Gastroenterology, Tower 2, 6th floor, Vaishali, A Unit of Crosslay Remedies Ltd., W-3, Sector-1, 201012 Ghaziabad UTTAR PRADESH
204173627
premashishkar@gmail.com
Dr Shrikant Vasantrao Mukewar
Midas Hospital
1st floor Research room, 392, Behind Empress Palace, Opposite Singh Saab Dhaba, Wardha Road, Parsodi, 441108 Nagpur MAHARASHTRA
77220033280
shrikant_mukewar@yahoo.com
Dr Devendra Desai
P.D. Hinduja National Hospital and Medical Research Center
Department of Gastroenterology, Room number 1106, Wing 1, 1st floor, OPD building, Veer Savarkar Marg, Mahim, 400016 Mumbai MAHARASHTRA
24457396
devendracdesai@gmail.com
Dr Mukesh Kalla
S R Kalla Memorial Gastro and General Hospital
Research Department, 4th Floor, 78-79, Dhuleshwar Garden, Behind HSBC Bank, Sardar Patel Marg, C-Scheme Jaipur RAJASTHAN
1414039432
drmkalla@rediffmail.com
Dr Hemant Kumar Gupta
Samvedna Hospital
Clinical Research Room, 4th Floor, Room number 401, B27/88G, New Colony, Ravindrapuri, 221005 Varanasi UTTAR PRADESH
9415336365
hemantkrg26@gmail.com
Dr Parth Shah
Sheth Vadilal Sarabhai General Hospital
Room no 2, burns wards second floor, OPD building, Madalpur Gam, Paldi Road, Ellisbridge, 380006 Ahmadabad GUJARAT
9924939099
doctorparthshah@gmail.com
Dr Chetan Mehta
Shree Giriraj Hospital
CRC Department, Room number CRC-3, First Floor, Navjyot Park Corner, 150 feet ring road, 360005 Rajkot GUJARAT
9825077472
mehtacn@hotmail.com
Dr Mayank Kabrawala
SIDS Hospital and Research Centre
Clinical Research Department, Ground Floor, A unit of SIDS Healthcare Pvt. Ltd., Off Ring Road, Near Shell Petrol Pump, Ring Road- Sosyo circle lane Surat GUJARAT
9825130363
mayankkabrawala@hotmail.com
Dr Ashish Kumar
Sir Ganga Ram Hospital
Sir Ganga Ram Hospital Marg, Clinical Research Room, 5th Floor, Lift No 12, Kitchen Building, Rajinder Nagar, 110060 New Delhi DELHI
7982907178
ashish10@yahoo.com
Dr Gaurav Kumar Gupta
SMS Super specialty Hospital
Department of Gastroenterology, Room number 217, 2nd floor, SMS Super specialty Hospital, Vivekanand Marg, C-Scheme, 302004 Jaipur RAJASTHAN
9214027938
drgauravsms@gmail.com
Dr Pankaj Jain
Sterling Hospital
Reva Block, 5th Floor, Clinical Research Department, Room No. 1205, Racecourse, Opp Inox, near Natubhai circle, Harinagar west, 390007 Vadodara GUJARAT
8347922004
jain_pass@yahoo.com
Dr Laxmikant Desai
Sushruta Multispecialty Hospital and Research Centre Multispeciality Pvt. Ltd.
Type: Recombinant humanized IgG1 monoclonal antibody
Dosage Form: Solution for infusion
Strength(s): 300 mg
Route of Administration: IV infusion
Presentation: Vial
Subjects will receive AVT16 300 mg IV once at Week 0, Week 2, Week 6, and every 8 weeks until Week 46 (14, 22, 30, 38, 46)
Comparator Agent
Entyvio
Type: Recombinant humanized IgG1 monoclonal antibody
Dosage Form: Solution for infusion
Strength(s): 300 mg
Route of Administration: IV infusion
Presentation: Vial
Subjects will receive Entyvio 300 mg IV once at Week 0, Week 2, Week 6, and every 8 weeks until Week 46 (14, 22, 30, 38, 46)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
1. Male or female subjects aged 18 to 80 years inclusive at the time of signing the informed consent form (ICF) who are voluntarily able to give informed consent.
2. Female subjects are eligible to participate if they are not pregnant, not breastfeeding, and at least ONE of the following conditions applies:
a. Is not a woman of childbearing potential (WOCBP), defined as:
- Surgically sterile (documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, as confirmed by review of the subject’s medical records, medical examination, or medical history interview), or
- Postmenopausal (defined as no menses for 12 months without an alternative medical cause). A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient). Female subjects on HRT and whose menopausal status is in doubt will be required to use 1 of the nonestrogen hormonal highly effective contraception methods from screening (signing the ICF) until at least 15 weeks after IP administration if they want to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment.
b. Is a WOCBP who agrees to use a highly effective method of contraception consistently and correctly from screening (signing the ICF) until at least 15 weeks after the last IP administration.
3. Nonsterilized male subjects with female partners of childbearing potential are eligible to participate if they agree to 1 of the following from screening (signing the ICF) until at least 15 weeks after IP administration:
a. Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.
b. Agree to use a male condom and have their partner use a contraceptive method with a failure rate of less than 1% per year when having penile vaginal intercourse with a WOCBP who is not currently pregnant.
c. Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile penetration.
d. In addition, male subjects must refrain from donating sperm from screening (signing the ICF) until at least 15 weeks after IP administration.
4. Diagnosis of UC established at least 3 months prior to baseline endoscopy by clinical and endoscopic evidence and corroborated by a histopathology report at Baseline.
5. Moderately to severely active UC as determined by a complete Mayo Score of 6 to 12 with an endoscopic subscore greater than or equal to 2 within 14 days prior to the first dose of IP.
6. Evidence of UC extending proximal to the rectum (greater than or equal to 15 cm from the anal verge) confirmed by endoscopy at least 3 months prior to baseline endoscopy.
7. Subjects with extensive colitis or pancolitis of more than or equal to 8 years duration or left sided colitis of more than or equal to 12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit (may be performed during screening).
8. Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age more than or equal to 50 years, or another known risk factor must be up to date on colorectal cancer surveillance (may be performed during screening).
9. Demonstrated, over the previous 5-year period, an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents as defined below:
a. Corticosteroids
- Signs and symptoms of persistently active disease despite a history of at least one 4-week induction regimen that included a dose equivalent to prednisone 30 mg daily orally for 2 weeks or IV for 1 week OR
- Two failed attempts to taper corticosteroids to below a dose equivalent to prednisone 10 mg daily orally OR
- History of intolerance of corticosteroids (including, but not limited to Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection).
b. Immunomodulators
- Signs and symptoms of persistently active disease despite a history of at least one 8-week regimen of oral azathioprine (greater than or equal to 1.5 mg/kg) or 6 mercaptopurine (greater than or equal to 0.75 mg/kg) OR
- History of intolerance of at least one immunomodulator (including, but not limited to, nausea/vomiting, abdominal pain, pancreatitis, liver function tests [LFT] abnormalities, lymphopenia, thiopurine methyltransferase [TPMT] genetic mutation, infection).
10. May be receiving a therapeutic dose of the following drugs:
a. Oral 5-aminosalicylic acid (5-ASA) compounds provided that the dose has been stable for the 2 weeks immediately prior to baseline endoscopy.
b. Oral corticosteroid therapy (prednisone at a stable dose less than or equal to 20 mg/day, or equivalent steroid) provided that the dose has been stable for 2 weeks prior to baseline endoscopy and must be stable for atleast two weeks after dosing.
c. Probiotics (eg, Culturelle, Saccharomyces boulardii) provided that the dose has been stable for the 2 weeks immediately prior to baseline endoscopy.
d. Antidiarrheals at a stable dose (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea.
e. Azathioprine or 6-mercaptopurine provided that the dose has been stable for the 8 weeks immediately prior to baseline endoscopy. Initiation or increase in dose leads to subject discontinuation.
ExclusionCriteria
Details
The exclusion criteria are divided into 3 categories as follows:
• gastrointestinal exclusion criteria,
• infectious disease exclusion criteria, and
• general exclusion criteria.
Subjects will be excluded from the study if any of the following criteria apply at any time starting from screening up to Day 0 prior to IP administration:
Gastrointestinal Exclusion Criteria
1. Evidence of abdominal abscess or toxic megacolon or fulminant stage of disease during the screening period.
2. Extensive colonic resection, subtotal, or total colectomy.
3. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
4. Prior treatment with TNF antagonist and/or any other biological therapy for UC.
5. Have received any of the following for the treatment of underlying disease:
a. Nonbiologic therapies (eg, cyclosporine, thalidomide) other than those permitted in the study if last dose was given 8 weeks prior to the baseline endoscopy.
b. A nonbiologic investigational therapy.
6. Use of topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline endoscopy.
7. Evidence of or treatment for Clostridium difficile infection within 60 days or other intestinal pathogen (eg, Salmonella, Escherichia coli, etc.) within 30 days prior to baseline endoscopy.
8. Currently require or are anticipated to require surgical intervention for UC during the study.
9. History or evidence of adenomatous colonic polyps that have not been removed.
10. History or evidence of any grade of colonic mucosal dysplasia.
11. Diagnosis of Crohn’s colitis or indeterminate colitis.
Infectious Disease Exclusion Criteria
12. Chronic hepatitis B or C infection.
13. Active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following:
a. History of TB.
b. A positive diagnostic TB test within 1 month of enrollment defined as:
- a positive QuantiFERON® test or 2 successive indeterminate QuantiFERON tests.
c. Chest X-ray within 3 months of enrollment in which active or latent pulmonary TB cannot be excluded.
Note: Subjects with an indeterminate QuantiFERON test are allowed if they have all of the following:
d. No evidence of active TB on chest radiograph within 3 months prior to the first dose of IP.
e. Documented history of at least 3 weeks of prophylaxis initiation prior to receiving IP in accordance with local recommendations and intend to complete its entire course during the study.
f. No known exposure to active TB after most recent prophylaxis.
g. Asymptomatic at Screening and Baseline.
Investigators should check with the medical monitor before enrolling such subjects.
14. Any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, HIV infection, organ transplantation).
15. Any live vaccinations within 30 days prior to IP administration except for an influenza vaccine.
16. Clinically significant extra-intestinal infection (eg, pneumonia, pyelonephritis) within 30 days prior to baseline endoscopy.
General Exclusion Criteria
17. Previous exposure to vedolizumab.
18. Female subjects who are lactating or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 0 prior to IP administration.
19. Any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise subject safety.
20. Have had any surgical procedure requiring general anesthesia within 30 days prior to baseline endoscopy or are planning to undergo major surgery during the study period.
21. Any history of malignancy, except for the following: (a) adequately treated nonmetastatic basal cell skin cancer; (b) any other type of nonmelanoma skin cancer that has been adequately treated and has not recurred for at least 5 years prior to baseline endoscopy; and (c) adequately treated in situ cervical cancer that has not recurred for at least 5 years prior to baseline endoscopy.
22. History of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.
23. Positive PML subjective symptom checklist prior to the administration of the first dose of IP.
24. Any clinically relevant laboratory abnormalities for hematology and for biochemistry tests of blood and urine during screening as judged by the principal investigator (PI).
25. Current or recent history (within 1 year prior to baseline endoscopy) of alcohol dependence or illicit drug use.
26. Active psychiatric problems that, in the investigator’s opinion, may interfere with compliance with the study procedures.
27. Any person for whom the following are true:
a. An employee of the study site, investigator, contract research organization (CRO), or sponsor.
b. A first-degree relative of an employee of the study site, the investigator, CRO, or sponsor.
c. Unable to attend all the study visits or comply with study procedures.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To demonstrate equivalent efficacy of AVT16 to Entyvio.
From baseline to Week 52
Secondary Outcome
Outcome
TimePoints
To further compare the efficacy of AVT16 with Entyvio.
From baseline to Week 52
To compare the safety of AVT16 with Entyvio.
From baseline to Week 52
To compare the immunogenicity of AVT16 with Entyvio.
From baseline to Week 52
To compare the PK of AVT16 with Entyvio.
From baseline to Week 52
Target Sample Size
Total Sample Size="748" Sample Size from India="109" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
07/03/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
05/09/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="2" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The study is a parallel-group, active comparator, multicenter study in subjects with moderate to severe active UC. It is a double-blind study wherein subjects and investigators will be blinded to the Investigational Product.
The study consists of a screening period (4 weeks), an active period (46 Weeks), and an end-of-study (EoS) visit (Week 52). The study duration will be up to 56 weeks including a 4-week screening period. The EoS visit will be at Week 52.
The Data Safety Monitoring Board (DSMB) will be an independent committee that will review and analyze on a regular basis, safety and efficacy data throughout the study.