Enrollment is nearing completion for two Phase 2 clinical trials testing the experimental treatment ELX-02 in people with cystic fibrosis (CF), according to Eloxx Pharmaceuticals, the company developing ELX-02.

“We expect full enrollment to be achieved during the first quarter of 2020, and to report topline results during the first half of 2020,” Eloxx stated in a press release.

ELX-02 is a eukaryotic ribosomal selective glycoside, a small molecule that works on ribosomes — the cellular machineries that translate messenger RNA into proteins.

CF is caused by mutations in the CFTR gene, which codes for a protein of the same name. Some of these mutations, called nonsense mutations, result in a stop codon within the gene. The stop codon causes ribosomes to stop making the complete CFTR protein, resulting in a half-finished protein that cannot carry out its function and is quickly degraded by the cell.

ELX-02 binds to ribosomes, and helps them read through these premature stop codons. Preclinical data suggest that this allows for the production of fully-functioning CFTR protein. Moreover, ELX-02 has shown a good safety profile in Phase 1 clinical trials in healthy volunteers (NCT02807961, NCT03292302, and NCT03309605).

The therapy is currently being tested in two Phase 2 clinical trials in CF patients who have at least one copy of the G542X allele, a nonsense mutation. A total of 24 participants are expected to be recruited in the EL-012 trial (NCT04135495) in Massachusetts, U.S., and in the EL-004 trial (NCT04126473) in Israel.

Both trials are funded by Eloxx. In addition, the U.S.-based EL-012 trial received funding from the Cystic Fibrosis Foundation.

The trials are open-label, meaning participants are aware that they will receive the therapy (and not a placebo). Each participant will receive four ascending doses of ELX-02, administered by subcutaneous (under-the-skin) injection. A low dose (0.3 mg/kg per day) will be administered first, followed by a dose increase per administration (0.75 and 1.5 mg/kg per day), up to 3.0 mg/kg per day.

The trials’ primary goal is to determine the safety of ELX-02 in people with CF, as assessed by the presence of adverse reactions. ELX-02’s pharmacokinetics and pharmacodynamics — how the therapy moves through and is processed by the body — will also be assessed.

Secondary outcomes include efficacy metrics, such as sweat chloride concentration and measurements of lung function.

More information about trial recruitment can be found here for EL-012, and here for EL-004.

In addition, Eloxx is also conducting clinical trials testing ELX-02 in other conditions that involve an aberrant stop codon, namely cystinosis.

Cystinosis is caused by mutations, including some nonsense mutations, in the CTNS gene. This leads to a buildup of the amino acid cysteine in the body, resulting in widespread toxicity.

A Phase 2 clinical trial (NCT04069260) being conducted in Canada is evaluating ELX-02 in people with nephropathic cystinosis, a form of the disease that affects the kidneys.

Preliminary data showed a decrease in cysteine levels in blood samples from some patients after ELX-02 treatment, and suggested that the therapy has a good safety profile, with the only reported adverse events being mild reactions at the injections site.