Study of the Safety and Tolerability of ALTH12 Versus Mesalamine Enema in Subjects With Left-Sided Ulcerative Colitis

Altheus Therapeutics

Status and phase: Completed; Phase 1

Conditions: Ulcerative Colitis

Treatments: Drug: ALTH12-1:4; Drug: mesalamine; Drug: ALTH12-2:4

Study type: Interventional

Funder types: Industry

Identifiers

NCT01020708

ALTH12-003

Details and patient eligibility

About

This Phase I study will be a closely monitored trial of a small number of subjects to establish, preliminarily, the tolerability and safety of two ALTH12 enema formulations: ALTH12-1:4 and ALTH12-2:4. The study will be conducted in two parts. The first part will be the assessment of the safety and tolerability of a single dose of ALTH12-1:4 or the comparator, mesalamine (4.0g 5-ASA) followed by an assessment of repeated administrations of study drug (ALTH12-1:4 or comparator) for 6 weeks. The second part will be the same assessment for ALTH12-2:4. Three subjects will be enrolled in each cohort: 2 to receive ALTH12 enema therapy and 1 subject to receive comparator enema therapy. A total of up to 9 patients will be enrolled in this study, allowing for up to 3 replacement or additional patients.

Enrollment: 9 estimated patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and female subjects are eligible if they are ≥ 18 years of age and ≤ 64 years

• They have a documented history of idiopathic ulcerative colitis based on endoscopic and/or histologic findings involving the left side of the colon, with mild active disease or disease in remission.

• Eligible subjects will have a documented history of ulcerative colitis, and a modified UCDAI with a sigmoidoscopy score of 1 point or less and Physician's rating of disease score of 1 point or less (mild or remission).

• Laboratory data:

  1. White blood cell count between 4,500 and 10,000 cells/mL
  2. Platelet count: 150,000-450,000 cells/mL
  3. Hemoglobin > 10.0 g/dL
  4. Total bilirubin < 1.5 mg/dL
  5. Aspartate aminotransferase < 100 u/dL
  6. Alanine aminotransferase < 100 u/dL
  7. Alkaline phosphatase < 250 u/dL
  8. Blood urine nitrogen < 40 mg/dL
  9. Creatinine < 1.5 mg/dL
  10. Amylase < 150 U/L

• Satisfied one of the following:

• Female subjects of childbearing potential must have a negative serum pregnancy test at screening; surgically sterile, post-menopausal, abstinent, or patient or partner agree to use a medically appropriate form of birth control from screening to until 1 month after the last dose of study medication.

• Male subjects must be surgically sterile, abstinent, or patient or partner compliant with a contraceptive regimen from screening to until 1 month after the last dose of study medication.

• They are able to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures.

Exclusion criteria

Subjects will be excluded if:

• They have documented history of proctitis or active proctitis confined to 15cm or less from the anal verge.
• They demonstrate signs and symptoms of fulminant colitis, bowel stricture, toxic megacolon, an anticipated need for blood transfusion for gastrointestinal bleeding, or demonstrate evidence of peritonitis.
• They receive a Physician's rating of disease severity as part of the modified UCDAI of 2 or greater (moderate or severe disease) or an endoscopy score of 2 or greater.
• They have shown evidence of high grade dysplasia on endoscopic examinations.
• Their stool contains enteric pathogens or Clostridium difficile toxins.
• They have a history of recurrent Clostridium difficile infection.
• They have prior history of biologic therapy.
• They have received systemic steroids or immunosuppressants within the previous 4 weeks.
• Treatment in the last 2 weeks that included antibiotic, antifungal, antiparasitic medications, or rectally administered steroids (e.g. Cortenema®) and/or 5-ASA enema (e.g. Rowasa®).
• They have a history of cancer (defined as malignancy within 5 years except for squamous cell or basal cell cancers of the skin), asthma, or bronchospasm.
• Positive pregnancy test or lactating subjects.
• There is evidence of chemical abuse.
• They have a known allergy to N-acetylcysteine or Mesalamine.
• They have a history of failure to retain enemas.
• Other clinically significant diseases that could interfere with the protocol compliance appear. These would include clinically important hematological, renal, hepatic, metabolic, psychiatric, central nervous system (CNS), pulmonary or cardiovascular disease.
• Any condition which the study physician judges to preclude safe participation in the study or to confound the evaluation of the study outcome.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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9 participants in 3 patient groups

Comparator

Active Comparator group

Description:

Mesalamine enema

Treatment:

Drug: mesalamine

ALTH12-1:4

Experimental group

Description:

ALTH12-1:4 experimental treatment dose

Treatment:

Drug: ALTH12-1:4

ALTH12-2:4

Experimental group

Description:

ALTH12-2:4 experimental treatment dose

Treatment:

Drug: ALTH12-2:4