Study to evaluate safety and efficacy of Novel Hydrocortisone Acetate 90 mg in Subjects with Ulcerative Colitis of the Rectum CHS1221
Scientific Title of Study
A Three-Arm, Randomized, Placebo-Controlled, Double-Blind Phase 3 Study to Evaluate the Safety and Efficacy of Once-Daily and Twice-Daily Dosing of a Novel Hydrocortisone Acetate 90 mg Suppository Formulation Administered with the Sephure® Suppository Applicator in Subjects with Ulcerative Colitis of the Rectum CHS1221
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NCT04469686
ClinicalTrials.gov
Protocol Number CHS1221 Ver 1.5 dated 03Feb2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
S. No. 235/2, B/s. Tata Motors Showroom Opposite Rajpath Club S.G. Highway, Bodakdev, Ahmedabad-380015,Gujarat, Ahmadabad GUJARAT
9727735536
drjigs2712@gmail.com
Dr Doiphode Mandar
Ashwin Medical Foundation Multi specialty Hospital.
Research department Opposite PMP Bus Stop, Powerhouse Chowk,Chinchwadgaon, Pune 411033 Pune MAHARASHTRA
9850077168
mandardoiphode22@gmail.com
Dr Kiran Jadhav
B.J Government Medical College and Sassoon General Hospitals
Railway Station Jai Prakash Narayan Road, Pune 411001, Maharashtra Pune MAHARASHTRA
7020880797
kirankumar@gmail.com
Dr Saumin Prakashbhai Shah
Gujarat Hospital
First Floor, Opposite Shree Ram Petrol Pump, Anand Mahal Rd, Adajan, Surat, Gujarat 395009 Surat GUJARAT
9408042224
dr.sauminpshah@gmail.com
Dr Manish Surajprakash Bhatnagar
ICON Hospital
Department of Gastroenterology, 3rd Floor,
ICON Hospital, Opposite Alpha One Mall Exit Beside Kalyan Pushti Haveli, Near Vastrapur Lake, Ahmedabad, Gujarat-380015
Ahmadabad GUJARAT
9825085059
bhatnagarclinic@yahoo.com
Dr Meghraj Ingle
Lokmanya Tilak Municipal Medical College & General Hospital Sion
Gastroenterology Department, 1st floor, Dr. Babasaheb Ambedkar Road, Sion, West Mumbai 400022,India Mumbai MAHARASHTRA
9320979659
drmeghraj@gmail.com
Dr Kaushal Madan
Max Smart Super Specialty Hospital
Press Enclave Marg, Max Smart Super Specialty Hospital Saket District Centre, New Delhi – 110017, New Delhi DELHI
9810688410
Kaushal.Madan@maxhealthcare.com
Dr Shrikant Mukewar
Midas Institute of Gastroenterology
Fourth Floor, Plot No.07, Midas Heights, Central Bazaar Road Ramdaspeth, Nagpur, Maharashtra, 440010 India Nagpur MAHARASHTRA
7720033280
shrikant_mukewar@yahoo.com
Dr Nripen Saikia
Pushpawati Singhania Research Institute
Press Enclave Marg, Sheikh Sarai, New Delhi-110017 New Delhi DELHI
9910847251
nripen@hotmail.com
Dr Ravindra Gaadhe
Sanjivani Super specialty Hospital
Research Department
1 New, Uday Park Society, Near Sunrise Park,
Vastrapur, Ahmedabad-380015,
Ahmadabad GUJARAT
9276558517
ravindragaadhe@gmail.com
Dr BSRamakrishna
SIMS Hospital
No.1 Jawaharlal Nehru Salai, Vadapalani Chennai 600026
Tamil Nadu,
Chennai TAMIL NADU
9994614890
drramakrishna.bs@simshospitals.com
Dr Shivam Khare
Sir Ganga Ram Hospital
Room F, 93, Sir Ganga Ram Hospital Marg, Block 8, Old Rajinder Nagar, Rajinder Nagar, New Delhi, Delhi 110060 New Delhi DELHI
9754478909
khare.shivam.shivam.1987@gmail.com
Dr Mukesh Kumar Jain
SMS Medical College & Hospital
Department of Gastroenterology S.M.S. Medical College, J.L.N. Marg, Jaipur-302004, Rajasthan, Jaipur RAJASTHAN
Hydrocortisone Acetate 90mg suppository BID
Hydrocortisone Acetate 90mg suppository OD
Comparator Agent
Placebo Suppository
Placebo Suppository OD
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1.Males or non-pregnant, non-lactating females aged 18 years and older.
2. Able to provide a signed informed consent.
3. Confirmed diagnosis of active UC of the rectum, extending no more than 15 cm (5.9 inches)
proximal to the anal verge as assessed by colonoscopy performed at Visit 2. Note: Subjects
may have a history of more extensive UC (e.g., pancolitis), but have active disease only in the
rectum at the time of enrollment.
4. Modified Mayo sub-score for stool frequency of 1-3 at Screening Visit (Visit 1) and Baseline
Visit (Visit 3).
5. Modified Mayo sub-score for rectal bleeding of 0-2 at Screening Visit (Visit 1) and Baseline
Visit (Visit 3).
6. Modified Mayo colonoscopy sub-score of 2-3 at Colonoscopy (Visit 2) as determined by
Central Reading.
7. Modified Mayo Total Score (without physician global assessment) of 3-8.
8. Females of childbearing potential must be either sexually inactive (abstinent) for 21 days prior
to the first dose and willing to be sexually inactive throughout the study or must be using one
of the following acceptable methods of birth control:
a) Surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) for a minimum period of 1 month prior to screening;
b) Intrauterine device in place for at least 1 month prior to screening;
c) Barrier methods (condom, diaphragm) with spermicide for
at least 21 days prior to screening and willing to continue throughout the study; or
d) Hormonal contraceptives for at least 6 weeks prior to screening.
9. Postmenopausal females with amenorrhea for at least 12 months prior to screening.
10. Subjects willing to abstain from receiving anal sex, anal bleaching, anal waxing, etc.
11. Availability of all the screening assessment results, such as: serum pregnancy test (for females of childbearing potential), medical history, concomitant medication, AEs, vital signs, physical examination, electrocardiogram (ECG), documented colonoscopy assessment, complete blood count, clinical chemistry and serology, urinalysis and stool test
results.
12. Subjects may be allowed to be re-screened for the study after consultation and approval from
the medical monitor but may be enrolled (randomized) only once.
ExclusionCriteria
Details
1. No colonic mucosal inflammation (absence of active disease) within 15 cm (5.9 inches) proximal to the
anal verge as assessed using the colonoscopy performed at Colonoscopy Visit (Visit 2).
2. Colonic mucosal inflammation extending beyond 15 cm (5.9 inches) proximal to the anal verge
as assessed using the colonoscopy performed at Colonoscopy Visit (Visit 2).
3. Preliminary endoscopic sub-score of 0 or 1 as assessed by the Investigator using the
colonoscopy performed at Colonoscopy Visit (Visit 2).
4. Endoscopic sub-score of 0 or 1 as assessed by the Central Reading using the colonoscopy
performed at Colonoscopy Visit (Visit 2).
5. History or current diagnosis of bacterial or other infectious colitis, radiation-enteritis and
radiation-proctitis, Crohn’s disease, collagenous colitis and indeterminate colitis.
6. Prior gastrointestinal surgery except appendectomy, cholecystectomy, and hernia.
7. Concomitant active gastrointestinal disease (except Irritable Bowel Syndrome) or distortion of
intestinal anatomy.
8. Bleeding hemorrhoids at the time of enrollment.
9. History of recurrent diverticulitis and/or diverticulitis at the time of enrollment.
10. History of recurrent pancreatic disease.
11. Uncontrolled, previously diagnosed type 1 or 2 diabetes mellitus.
12. Uncontrolled abnormal thyroid function.
13. Mean value for triplicate sitting SBP >160 mm Hg and/or DBP >100 mm Hg after at least a 5-
minute seated rest at the Screening visit. The Investigator or the treating physician is allowed
to adjust background blood pressure medication(s) to lower blood pressure values in order for the subject to be re-assessed for enrollment eligibility.
14. Clinically significant ECG abnormality at screening that requires further diagnostic evaluation or intervention (e.g., new, clinically significant arrhythmia or a conduction disturbance).
15. Serum hemoglobin levels <7.5 g/dL.
16. Indication of impaired liver function as shown by an abnormal liver function profile at Screening (e.g., repeated values of aspartate aminotransferase [AST] and alanine
aminotransferase [ALT] ≥ 2 × the upper limit of normal).
17. History of sclerosing cholangitis, cirrhosis, or hepatic impairment.
18. Renal disease manifested by serum creatinine >2.0 mg/dL.
19. History of avascular necrosis of hip.
20. History or signs/symptoms of or positive test result at screening for cytomegalovirus,
tuberculosis, human immunodeficiency virus, hepatitis B or C infection.
21. History or signs/symptoms of ocular herpes simplex or ocular varicella zoster infection.
22. History of malignant disease, with the exception of basal cell carcinoma; squamous cell carcinoma in situ of the skin; cervical carcinoma in situ that has been treated with no evidence of recurrence; or squamous cell carcinoma of the skin that has been treated with no evidence of recurrence within 5 years prior to screening.
23. Diagnosis of Addison’s disease, congenital adrenal hyperplasia, or other form of adrenal insufficiency.
24. Subjects with abnormal response to the ACTH stimulation test performed at the screening visit (Visit 1).
25. Active systemic infection.
26. Toxic megacolon, fistula, perforation, or abscess.
27. History of uncontrolled psychiatric disorders or seizure disorders.
28. History of non-responsive UC to steroid treatment.
29. History of medical condition requiring use of inhaled steroids during the study (for treatment of asthma, COPD, etc.).
30. History of drug or alcohol abuse within the last 6 months. Alcohol abuse is defined as more than 14 drinks per week for men and more than 7 drinks per week for women.
31. Other current diagnosis of severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, psychiatric, or cerebral diseases.
32. History of evidence of any medical condition that would, in the opinion of the Investigator, make the subject unsuitable for the study.
33. Positive stool test result at screening for enteric pathogens, Clostridium difficile, or presence of ova and parasites.
34. Vaccination with live vaccine within 28 days prior to randomization. However, attenuated vaccine is allowed.
35. Allergies to hydrocortisone acetate or to any other ingredients of the investigational product.
36. Taking a permitted medication outside of the permitted criteria (Section 5.7.1).
37. Taking a prohibited medication (Section 5.7.2).
38. Pregnant, confirmed with a positive serum test for pregnancy at screening, or lactating females and females of childbearing potential who do not meet the inclusion criteria (Section 4.1).
39. Participation in another research study for an investigational drug within 30 days of the Screening Visit and during the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To evaluate the efficacy of two dosage regimens of the study drug (90 mg hydrocortisone suppository) administered with Sephure suppository applicator compared to placebo in the treatment of UC of the rectum using the Modified Mayo Score.
End of treatment
Secondary Outcome
Outcome
TimePoints
The following secondary objectives will be evaluated hierarchically with Baseline (Day 1/Visit 3) compared to End of Treatment (Day 29/Visit 7) and then Follow Up (Day 15/Visit 5):
Reduction of stool frequency.
Rectal bleeding sub-score of 0 (MMDAI).
End of treatment
Target Sample Size
Total Sample Size="114" Sample Size from India="114" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This
is a Three-Arm, Randomized, Placebo-Controlled, Double-Blind Phase 3 Study to
Evaluate the Safety and Efficacy of Once-Daily and Twice-Daily Dosing of a
Novel Hydrocortisone Acetate 90 mg Suppository Formulation Administered with
the Sephure® Suppository Applicator in Subjects with Ulcerative Colitis of the
Rectum.
Ulcerative colitis (UC), an inflammatory bowel disease (IBD),
is a chronic disease which is characterized by diffuse mucosal inflammation. It usually
begins in the rectum and the lower colon but may also spread continuously to involve the entire colon.
Approximately 907,000 individuals in the United States (US) are affected by UC,
with an incidence rate of 12.2 per 100,000 population per year.
Cristcot HCA LLC has developed a suppository formulation containing
90 mg of hydrocortisone acetate (equivalent to 80 mg hydrocortisone base) per
suppository. This is paired with a unique applicator (Sephure suppository applicator) to optimize
delivery of the suppository into the rectum and reduce the potential for the suppository to be expelled.
This targeted therapy for UC of the rectum will reduce exposure of healthy gastrointestinal
tissue to medication unnecessarily.
Additionally, the ease and hygiene associated with the use of
the Sephure suppository applicator may promote better subject compliance to the medication.
The present study will evaluate the safety and efficacy of
two dosage regimens of the study drug (90 mg hydrocortisone acetate suppository with Sephure
suppository applicator) compared with placebo in the treatment of UC of the rectum. UC of the
rectum is defined as subjects with UC extending to no more than 15 cm (5.9 inches) proximal to the
anal verge. The study will only enroll subjects with a Modified Mayo Score (without physician
global assessment) of 3-8, and Modified Mayo sub-scores of 1-3 for stool frequency, 0-2 for
rectal bleeding, and 2-3 for
colonoscopy at screening. The study will also evaluate
systemic exposure to hydrocortisone and hydrocortisone acetate following administration of the study
drug.