Foralumab Clinical trials
Ongoing Phase 1 Clinical Trial: Nasal Administration of Foralumab for the Treatment of Multiple Sclerosis
The completed Phase 1 clinical trial of Foralumab in healthy volunteers was a single center, single arm, ascending dose study in which low doses (10, 50 and 250 µg/dose) of Foralumab and placebo were nasally administered for 5 consecutive days. Subjects were monitored for tolerance and immunological effects. The primary endpoint of the Phase 1 study is safety, tolerability and biomarkers of immunomodulation of clinical responses of intra nasally administered Foralumab. Interim results have indicated no drug-related safety issues so far. Topline results are expected in the third quarter of 2019. Phase 2a trials will be initiated at a later date for the treatment of MS assuming positive tolerability data the from Phase 1 trial.
Proposed Phase 1 Clinical Trial: Oral Administration of Foralumab in Healthy Volunteers
An enteric-coated capsule formulation has been developed for oral administration of Foralumab. cGMP manufacturing of clinical trial materials for a Phase 1 study has been completed and we have submitted an IND for this study. The proposed Phase 1 clinical trial for Foralumab in healthy volunteers is a single-center, single-arm, ascending dose study in which low doses (0.5, 1.25, 2.5 and 5.0 mg/dose) of Foralumab and placebo will be orally administered. The primary endpoint of the Phase 1 study is safety and tolerability of oral Foralumab in humans. We submitted an IND on March 18, 2019, to the FDA. The FDA requested safety data from the phase 1 trial with nasal administration of Foralumab to justify the proposed dose-range for the phase 1 trial with oral administration of enteric-coated capsules of Foralumab in healthy volunteers. We withdrew the current IND on April 17, 2019. A Type B pre-IND meeting was held with the FDA (GI division, Crohn’s Disease) on July 24, 2019. The FDA provided clear guidance on design of the clinical trials in healthy subjects. A revised IND will be submitted following FDA review of safety data from the nasal trial. We expect to initiate a Phase 1 trial of the oral, enteric capsule formulation of Foralumab in healthy subjects in the second half of 2019.
Proposed Phase 2 Clinical Trial: Foralumab for the Treatment of NASH
Based on the outcomes of the Phase 1 trial, a Phase 2 clinical trial in NASH patients will be proposed. Oral Foralumab will be evaluated in a randomized, placebo-controlled, four-arm, double-blinded study. The Company intends to enroll 48 patients in the trial who will receive either a once- daily oral placebo or Foralumab dose (established from the Phase 1 study) for 30 consecutive days.
The safety and tolerability of the treatment regimen is the primary endpoint of the study and will be determined by monitoring vital signs, laboratory values, adverse events and physical findings throughout the study. In addition, efficacy/immunomodulatory activity will be established using the following criteria: (1) reduced day 30 serum alanine aminotransferase (ALT) levels; (2) reduced hemoglobin A1c; (3) improved homeostasis model assessment (HOMA); (4) HOMA of insulin resistance (HOMA-IR) scores; as well as (5) levels of T cells and cytokines as compared to baseline (Day 1).
Prior Novimmune Clinical Trials using Intravenous Foralumab
Intravenous Foralumab has been studied in one Phase 1 and two Phase 2 clinical trials (Chron’s disease https://clinicaltrials.gov/ct2/show/NCT00630643 and patients With Acute Renal Allograft Rejection https://clinicaltrials.gov/ct2/show/NCT00805909) conducted by Novimmune. A total of 68 patients were administered Foralumab:
- The short-term tolerability profile of Foralumab was very similar to those reported with other anti-CD3 antibodies and no new emerging concerns have been identified.
- Total daily doses of up to 1mg (~ 500 µg/m2) per patient were generally well tolerated without corticosteroid premedication with reduction in the Crohn’s Disease Activity Index (CDAI) scores in patients.
- The most common adverse events following exposure to Foralumab were Infusion Related Reactions (IRRs).
- A clear reduction of IRRs was observed with steroid pre-medication up to 2.5 mg/dose for 5 consecutive days.
- Therefore, usage of steroid pre-medication allows the administration of higher doses.
- Both the magnitude and duration of CD3 modulation increased in a dose related manner.
- No anti-drug antibodies were detected