This Phase 2a study evaluated the efficacy, safety, and tolerability of intravenous human placenta-derived cells (PDA001) compared with placebo in adults with moderate-to-severe Crohn's disease. Three PDA001 dose levels were evaluated.

This was a Phase 2a, multicenter study designed to evaluate the safety, tolerability, and efficacy of intravenous human placenta-derived cells (PDA001) in adults with moderate-to-severe Crohn's disease.

The study consisted of sequential cohorts. Initial open-label dose-escalation cohorts evaluated PDA001 administered intravenously at a dose of 1.6 × 10^9 cells (8 units). A subsequent randomized, double-blind, placebo-controlled cohort evaluated PDA001 administered intravenously at doses of 200 × 10^6 cells (1 unit) and 800 × 10^6 cells (4 units) compared with placebo.

The primary efficacy objective was to evaluate induction of clinical response, defined as a reduction from baseline of 25% and/or at least 100 points in the Crohn's Disease Activity Index (CDAI) at both Week 4 and Week 6. Secondary objectives included evaluation of clinical remission, safety, and tolerability.

Subjects were followed during an induction phase and could participate in an extension phase with re-treatment according to protocol-defined criteria.

Inclusion Criteria:

1. Males and females ages 18-75 years
2. Understand and voluntarily sign an informed consent
3. Able to adhere to the study visit schedule and other protocol requirements
4. Minimum weight of 50 kg
5. A female of childbearing potential (FCBP)† must have a negative urine pregnancy test at screening (Visit 1) and immediately prior to all doses of IP. In addition, sexually active FCBP must agree to use two of the adequate forms of contraception methods for the duration of the study and the follow-up period. A FCBP must agree to have pregnancy tests at least every 4 weeks during the study. Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in reproductive sexual activity with FCBP for the duration of the study and the follow-up period.
6. Subject must have inflammatory CD 6 months prior to treatment and have confirmation of ongoing disease activity by colonoscopy or (other method) at screening
7. Subject must have a CDAI score > 220 and < 450 as assessed between Visit 1 and Visit 2
8. The Subject must have failed, i.e., had an inadequate response or lost response (recurrence of symptoms) to an agent, or documented intolerance to an agent at any time

Exclusion Criteria:

1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study

A female of childbearing potential is a sexually mature woman who:

1. has not undergone a hysterectomy or bilateral oophorectomy
2. has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Cohort 2 was conducted as a randomized, double-blind, placebo-controlled study. Participants, care providers, investigators, and outcomes assessors were blinded to treatment assignment. Initial dose-escalation cohorts were conducted open-label.