A Study of Roginolisib in Combination With Ruxolitinib in Patients With Myelofibrosis (MF) Who Are Unresponsive to JAK Inhibitors

NCT06887803 | Recruiting Phase 1 DMC

• 2 other identifiers: IOA-244-2032024-515252-20
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 11

Brief Summary

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.

Conditions

Myelofibrosis (MF)

Keywords

Myelofibrosis

Outcome Measures

Primary Outcomes (4)

• Number of participants with treatment emergent adverse events

  Safety measure by Adverse Event's

  Day 1 and 15 of cycle 1; Day 1 of each subsequent cycle whilst on treatment anticipated to be 52 weeks. Cycle length 28 days

• Number of Participants with abnormal ECG recordings

  Changes observed on 12-lead ECG

  Day 1 of each cycle whilst on treatment anticipated to be 52 weeks. Cycle length 28 days

• Number of participants with abnormal laboratory parameters

  Standard laboratory parameters (including clinical chemistry, heamatology)

  Day 1 and 15 of cycle 1; Day 1 of each subsequent cycle whilst on treatment anticipated to be 52 weeks. Cycle length 28 days

• Number of participants with changes in blood pressure measurements

  As measured by blood pressure measurements

  Day 1 and 15 of cycle 1; Day 1 of each subsequent cycle whilst on treatment anticipated to be 52 weeks. Cycle length 28 days

Secondary Outcomes (6)

• To evaluate biomarker responses (e.g., Treg reduction) when roginolisib is administered in combination with ruxolitinib in patients with MF.

  Day 1 of Cycle 1, 2 and 3 and then Day 1 of every other cycle (C5, C7 etc) until end of treatment anticipated to be 52 weeks. Cycle length is 28 days

• Spleen reduction responses of roginolisib when administered in combination with ruxolitinib in patients with MF.

  Splenic response rate at baseline, 12 and 24 weeks. Duration of spleen response every 12 weeks whilst on treatment anticipated to be 52 weeks.

• To evaluate preliminary signs of clinical efficacy of roginolisib when given in combination with ruxolitinib

  Patients will be followed up for overall survival every 12 weeks, for 96 weeks from last patient enrolled, until their death or end of the study

• 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)

  TTS and MFSAF measured at baseline and at 12 and 24 weeks.

• To determine the pharmacokinetic (PK) parameters of roginolisib when given in combination with ruxolitinib to allow exposure/response and/or exposure/safety assessment

  Day 1 of each cycle whilst on treatment anticipated to be 52 weeks. Cycle length 28 days

Study Arms (1)

Single Arm

EXPERIMENTAL

Roginolisib and ruxolitinib

Drug: Roginolisib

Interventions

Roginolisib DRUG

IOA-244: 80 mg (corresponding to 72 mg roginolisib) Ruxolitinib: up to 25 mg BD

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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)
• Dynamic International Prognostic Scoring System (DIPSS) risk category of intermediate-1, intermediate-2, or high
• Treated with ruxolitinib for ≥ 3 months with a stable dose ≥ 10 mg for a minimum of 8 weeks prior to Day 1. Furthermore, patients must show an unsatisfactory spleen reduction, such as a reduction of less than 25%, and spleen must be palpable ≥ 10 cm below the left costal margin on physical examination
• Did not receive experimental drug therapy for MF or any other drug considered as an effective treatment for MF (e.g., danazol, hydroxyurea, interferon products) with the exception of ruxolitinib, within 3 months of starting study drug (except in conditions where other effective treatments for MF were completed 6 months prior to starting ruxolitinib)
• Independent of spleen size, active symptoms of MF at the screening visit, as demonstrated by the presence of a Total Symptom Score (TSS) of ≥ 10 using the Screening Symptom Form.
• Peripheral blast count \< 10%
• Act to avoid pregnancy or fathering children based on the criteria below:
• Women of non-childbearing potential (i.e., surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of age).
• Women of childbearing potential who had a negative serum pregnancy test at screening and who agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up, at least 1 month after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the patient and their understanding confirmed.
• Men who agree to take appropriate precautions to avoid fathering from screening through safety follow-up, at least 1 month after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix 3) should be communicated to the patient and their understanding confirmed.

You may not qualify if:

• 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.
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrolment), myocardial infarction (\< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• Patients with active malignancy requiring concurrent intervention or previous malignancies unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period and the patient is assessed at low risk of relapse by the investigator. Note: Patients with a slow progressing cancer (e.g. prostate) or an in situ cancers (e.g. cervical dysplasia) are permitted.
• Any serious or uncontrolled medical disorder or active infection that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy.
• Use of the following treatments within the time periods noted:
• Erythropoiesis stimulating agent (ESA) within 4 weeks prior to start of roginolisib.
• Splenic irradiation within 3 months prior to start of roginolisib.
• Receiving an immune-suppressive based treatment for any reason (including chronic use of systemic corticosteroid at doses \> 10 mg/day prednisone equivalent) within 14 days prior to the first dose of study treatment. Use of inhaled or topical steroids (including but not limited to creams or intra-articular injection) or brief corticosteroid use for radiographic procedures or systemic corticosteroids ≤ 10 mg is permitted.
• Have received a live vaccine within 30 days of planned start of study therapy while on trial. Other type of vaccines, including SARS-Co2 vaccines, are allowed.
• Known allergy or reaction to any component of either study drugs or formulation components.
• Currently breastfeeding.
• Known alcohol or other substance abuse.

Sponsors & Collaborators

• iOnctura: lead

Study Sites (11)

Azienda Ospedaliero Universitaria Careggi Firenze, Struttura Complessa di Ematologia

Florence, Florence, 50134, Italy

RECRUITING

IRCCS Clinical Institute Humanitas

Rozzano, Milan, 20089, Italy

RECRUITING

Istituto di Ematolgia e Oncologia Medica

Bologna, 40138, Italy

RECRUITING

Azienda Sanitario Universitaria Friuli Centrale

Udine, 33100, Italy

RECRUITING

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

RECRUITING

Avigunda Gran via de l'Hospitalet 199-203, 08908 L'Hospitalet de Llobregat

Barcelona, 08908, Spain

RECRUITING

START Madrid CIOCC

Madrid, 28050, Spain

NOT YET RECRUITING

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

RECRUITING

United Lincolnshire Teach Hospitals NHS Trust, Pilgrim Hospital Boston

Boston, Lincolnshire, PE21 9QS, United Kingdom

NOT YET RECRUITING

Belfast City Hospital

Belfast, BT9&AB, United Kingdom

NOT YET RECRUITING

Guy´s and St. Thomas NHS Foundation Trust

London, SE1 9RT, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Michael Lahn, Dr

  iOnctura

  STUDY DIRECTOR

Central Study Contacts

Tracey Hammett, RN

CONTACT

+44 7776498978; t.hammett@ionctura.com

Karen Tonge

CONTACT

+44 7770678446; k.tonge@ionctura.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Arm, open-label

Study Record Dates

• First Submitted: February 26, 2025
• First Posted: March 20, 2025
• Study Start: November 17, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

GB (3); IT (4); ES (4)