The goal of this clinical trial is to learn how roginolisib works in comparison to standard treatment in adult patients with Myelofibrosis. The main questions it aims to answer is to evaluate the safety and tolerability of roginolisib when administered in combination with ruxolitinib.
≥18 years of age inclusive, at the time of signing the informed consent.
Capable of giving signed informed consent, which includes compliance with the requirements of this protocol.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Diagnosis of MF, Post-Polycythaemia Vera Myelofibrosis MF (PPV-MF), or post-essential thrombocythemia MF (PET-MF)
Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
History of a prior Grade 3 or 4 AE which did not respond to therapy or resolved with treatment interruptions and returned to at least Grade 1, other than fatigue. Note: Patients with ≤ Grade 2 neuropathy or alopecia are an exception and may enrol.
Active autoimmune process (e.g., rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease, immune colitis) for which systemic treatment (i.e., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) is required. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
History or presence of an abnormal ECG that, in the Investigator's opinion, is clinically meaningful. Screening QTc interval > 480 milliseconds is excluded (corrected by Fridericia). In the event that a single QTc is > 480 milliseconds, the patient may enrol if the average QTc for the 3 ECGs is < 480 milliseconds. For patients with an intraventricular conduction delay (QRS interval > 120 msec), the JTc interval may be used in place of the QTc with Sponsor approval. The JTc must be < 340 milliseconds if JTc is used in place of the QTc. Patients with left bundle branch block are excluded.
Single group
Roginolisib
DrugIOA-244: 80 mg (corresponding to 72 mg roginolisib) Ruxolitinib: up to 25 mg BD
Number of participants with treatment emergent adverse events
Safety measure by Adverse Event's
Number of Participants with abnormal ECG recordings
Changes observed on 12-lead ECG
Number of participants with abnormal laboratory parameters
Standard laboratory parameters (including clinical chemistry, heamatology)
Number of participants with changes in blood pressure measurements
As measured by blood pressure measurements
To evaluate biomarker responses (e.g., Treg reduction) when roginolisib is administered in combination with ruxolitinib in patients with MF.
Changes in peripheral blood Tregs from baseline at Week 12 and continued reduction over time
Spleen reduction responses of roginolisib when administered in combination with ruxolitinib in patients with MF.
Splenic response rate (SRR) of ≥15%, ≥25% and ≥35% reduction in spleen volume as assessed by MRI/CT Duration of spleen response
To evaluate preliminary signs of clinical efficacy of roginolisib when given in combination with ruxolitinib
Proportion of patients with transfusion independence at 12 and 24 weeks where applicable
To determine the improvements of MF related symptoms when roginolisib is given in combination with ruxolitinib as assessed by the Myelofibrosis Symptom Assessment Form (MFSAF)
Proportion of patients who have any reduction in Total Symptom Score (TSS) at 12 and 24 weeks compared to baseline as measured by Myelofibrosis Symptom Assessment Form (MFSAF) Proportion of patients who have a reduction of ≥25% and ≥50% in TSS as measured by Myelofibrosis Symptom Assessment Form (MFSAF) Mean change in TSS as measured by Myelofibrosis Symptom Assessment Form (MFSAF) Time to the first ≥50% reduction compared to baseline in TSS as measured by Myelofibrosis Symptom Assessment Form (MFSAF) Duration of TSS response as measured by MFSAF (e.g., duration of TSS ≥25% and ≥50%)
