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CTRI Number  CTRI/2023/11/059758 [Registered on: 13/11/2023] Trial Registered Prospectively
Last Modified On: 29/02/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Other 
Public Title of Study   A study of HT-6184 in subjects with Myelodysplastic Syndrome (MDS) and Symptomatic Anemia. 
Scientific Title of Study   A Phase 2a study of HT-6184 in subjects with IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndrome (MDS) and Symptomatic Anemia. 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
HT-6184-MDS-001 Version No. 3.0 dated 15/May/2023   Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Sandeep Singh 
Designation  Vice President - Clinical Operations 
Affiliation  CBCC Global Research LLP 
Address  TURQUOISE-IV, 6th Floor, Sardar Patel Ring Rd, Opp. Apple Woods, Near Shantipura circle, Ahmedabad- 382210, Gujarat, India.

Ahmadabad
GUJARAT
382210
India 
Phone  9637555304  
Fax    
Email  sandeep.singh@cbccusa.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Sandeep Singh 
Designation  Vice President - Clinical Operations 
Affiliation  CBCC Global Research LLP 
Address  TURQUOISE-IV, 6th Floor, Sardar Patel Ring Rd, Opp. Apple Woods, Near Shantipura circle, Ahmedabad- 382210, Gujarat, India.

Ahmadabad
GUJARAT
382210
India 
Phone  9637555304  
Fax    
Email  sandeep.singh@cbccusa.com  
 
Details of Contact Person
Public Query  
Name  Dr Sandeep Singh 
Designation  Vice President - Clinical Operations 
Affiliation  CBCC Global Research LLP 
Address  TURQUOISE-IV, 6th Floor, Sardar Patel Ring Rd, Opp. Apple Woods, Near Shantipura circle, Ahmedabad- 382210, Gujarat, India.

Ahmadabad
GUJARAT
382210
India 
Phone  9637555304  
Fax    
Email  sandeep.singh@cbccusa.com  
 
Source of Monetary or Material Support  
Halia Therapeutics, 1865 West 2100 South, Ste 100 Salt Lake City, Utah 84119  
 
Primary Sponsor  
Name  Halia Therapeutics 
Address  1865 West 2100 South, Ste 100 Salt Lake City, Utah 84119. Phone:13853554315 Fax:6319241731  
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NA  NIL 
 
Countries of Recruitment     India
United States of America  
Sites of Study
Modification(s)  
No of Sites = 10  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Uttam Kumar Nath  All India Institute of Medical Sciences  Department of Medical Oncology Hematology, Virbhadra Road, Rishikesh, Dist-Dehradun-249203, Uttarakhand, India
Dehradun
UTTARANCHAL 		 9433982756

uttam.haemat@aiimsrishikesh.edu.in 
Dr Srinivas Chakravarthy  Apollo Cancer Centre  Road No. 92, Jubilee Hills, Hyderabad- 500033, Telangana, India
Hyderabad
TELANGANA 		 9989299091

halarusri@yahoo.com 
Dr Varun Bafna  Dr. Bafnas Star Superspeciality clinic and Hospital  Ruikar colony and ward, Near LIC ground, Kolhapur-416005, Maharashtra, India
Kolhapur
MAHARASHTRA 		 9066565353

drvarunbafna6@gmail.com 
Dr Ramesh Uppada  HCG Cancer Center Vizag  Plot No. 10, Survey No. 13P, APIIC Health City, Arilova, Chinnagadili- 530040, Andhra Pradesh, India
Krishna
ANDHRA PRADESH 		 9494708778

drramesh.u@hcgel.com 
Dr Sandip Shah  Hemato Oncology Clinic Ahmedabad Pvt. Ltd., Vedanta Institute of Medical Sciences  Near Samved Hospital, Stadium Commerce College Road, Navrangpura, Ahmedabad - 380009, Gujarat, India
Ahmadabad
GUJARAT 		 9099007706

sandip60@yahoo.com 
Dr Chandran K Nair  Malabar Cancer Centre  Thalassery, P.O., Moozhikkara, Kannur-670103, Kerala, India
Kannur
KERALA 		 9496048808

cknair09@gmail.com 
Dr Kasi Viswanathan  Meenakshi Mission Hospital and Research Centre  Lake area, Melur road, Madurai- 625107, Tamilnadu, India
Madurai
TAMIL NADU 		 9965606712

kasi.mmhrc@gmail.com 
Dr Tuphan Kanti Duloi  Nil Ratan Sircar medical college and Hospital  138 AJC Box Road, Kolkata 700014, West Bengal, India
Kolkata
WEST BENGAL 		 9874890275

tkdolai@hotmail.com 
Dr Aishwarya Raj  Shalby Hospital  Opp. Karnavati Club, Sarkhej - Gandhinagar Highway, Ahmedabad - 380015, Gujarat, India
Ahmadabad
GUJARAT 		 9877745882

hematology1.sg@shalby.in 
Dr Arijit Nag  Tata Medical Center  14, Major arterial road (EW), Newtown, Rajarhat, Kolkata-700160, West Bengal, India
Kolkata
WEST BENGAL 		 9051121161

arijit.nag@tmckolkata.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 10  
Name of Committee  Approval Status 
Ethics committee of CIMS, Care Institute of Medical Sciences  Approved 
Ethics Committee, N.R.S. Medical College   Approved 
Ethics Committee-Shalby Limited  Submittted/Under Review 
IEC-Mahatma Gandhi Cancer Hospital   Approved 
Institutional Ethics Committee AIIMS Rishikesh  Approved 
Institutional Ethics Committee HCG Cancer Centre  Approved 
Institutional Ethics Committee Malabar Cancer Centre  Approved 
Institutional Ethics Committee Meenakshi Mission Hospital and Research Centre  Approved 
Institutional Ethics Committee-Clinical Studies Apollo Hospitals Enterprise Limited  Approved 
Institutional Review Board, Tata Medical Center  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: D469||Myelodysplastic syndrome, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  HT-6184 2 mg capsule for 4-month (32-weeks) of Halia Therapeutics.  Dose: 2 mg, Frequency: administration for 5 days followed by a 2 days drug holiday, Route of Administration: Oral, Duration of Therapy: The duration from the screening visit until the end of study assessment  
Comparator Agent  NA  NIL 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  90.00 Year(s)
Gender  Both 
Details  1. Subjects greater than or equal to 18 years of age
2. Subject has signed the Informed Consent Form (ICF) and is able to comply with scheduled visits, treatment schedule, laboratory tests, bone marrow aspirates collection, biopsy and other protocol requirements.
3. Adequate organ function as defined by the following laboratory values
a) Serum creatinine less than 2.0 X ULN
b) AST and ALT less than 3.0 X ULN
c) Total bilirubin less than 1.5 X ULN (or total bilirubin less than or equal to 3.0 x ULN with direct bilirubin within normal range only in subjects with well documented Gilberts syndrome or hemolysis or who required regular blood transfusions)
4. A documented diagnosis of MDS or non-proliferative (WBC less than 13,000 per micro L) myelodysplastic or myeloproliferative neoplasm (MDS or MPN) according to World Health Organization (WHO) 2022 classification and Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease (refer Appendix C)
Following MDS subjects as per WHO 2022 criteria are eligible (refer Appendix D)
MDS with low blasts and isolated 5q deletion (MDS-5q)
MDS with low blasts and SF3B1 mutation (MDS-SF3B1)
MDS with low blasts (MDS-LB)
MDS, hypoplastic (MDS-h)
MDS with increased blasts (MDS-IB) MDS-IB1
Following non-proliferative MDS or MPN subjects as per WHO 2022 criteria are eligible (refer Appendix E)
Chronic myelomonocytic leukaemia Myelodysplastic or myeloproliferative neoplasm with neutrophilia Myelodysplastic or myeloproliferative neoplasm with SF3B1 mutation and thrombocytosis Myelodysplastic or myeloproliferative neoplasm, not otherwise specified
5. Less than 10 percent bone marrow myeloblasts
6. Refractory or intolerant of, or ineligible for treatment with an erythroid stimulating agent (ESA) as defined by any of the following
a) Refractory to prior ESA treatment: Prior treatment with an ESA without response or no longer responding to an ESA alone or in combination with a myeloid growth factor (must have received recombinant erythropoietin (rHu EPO) with epoetin alfa greater than or equal to 40,000 IU per week for greater than 8 weeks or darbepoetin alpha 300-500 micro g Q 2-3 W for greater than 8 week
b) Intolerant to prior ESA treatment Intolerant to prior ESA treatment with documentation of discontinuation due to intolerance or adverse event.
c) ESA ineligible: Subject may be ESA ineligible due to low probability of response to ESAs based upon endogenous serum erythropoietin level greater than 200 U per L for subjects not previously treated with ESAs
7. Prior ESA treatment must have been discontinued greater than or equal to 2 weeks prior to date of study treatment
8. Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2. (refer appendix A)
9. Subjects must have symptomatic anemia with non-transfused hemoglobin less than 9.0 g per dL within 8 weeks of screening or red blood cell (RBC) transfusion-dependent defined as receiving greater than 3 units of PRBCs in the preceding 16 weeks of screening for a hemoglobin less than9.0g per dL.
10. NGS (Next-generation sequencing) myeloid specific somatic gene mutation profile where applicable with greater than or equal to 5 percent quantitation of clone size by variant allele frequency (VAF).
11. Women of child bearing potential, (defined as women physiologically capable of becoming pregnant, unless they are using effective method of contraception during dosing of the investigational product) practicing acceptable methods of contraception during the study.
Acceptable methods of contraception are
a) Intrauterine device or intrauterine system
b) Double barrier method of contraception (Condom and occlusive cap or condom and spermicidal agent)
c) Male sterilization (at least 6 months prior to the screening, should be the sole male partner for that subject)
d) Female sterilization (surgical bilateral oophorectomy) or tubal ligation at least 6 weeks prior to study participation
e) Total abstinence, partial abstinence is not acceptable
 
 
ExclusionCriteria 
Details  1. Other causes of anemia such as iron deficiency. Subjects must have documented marrow iron stores or serum ferritin >50 ng/ml. If marrow iron store is not available, the transferrin saturation must be > 20% or a serum ferritin > 50 ng/ mL.
2. Clinically significant anemia resulting from B12 or folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding.
3. Women must not be pregnant or breastfeeding. Females of childbearing potential should have a negative pregnancy test (sensitivity of at least 50 mIU/mL) within 28 days of first dosing and negative urine pregnancy test on day 1 of cycle 1.
4. Presence of concomitant intercurrent illness, or any condition which in the opinion of the Investigator, would compromise safe participation in the study, e.g. active
severe infection, uncontrolled hypertension, uncontrolled seizure, unstable angina pectoris, new onset of exacerbation of a cardiac arrhythmia
5. Secondary MDS, defined as MDS that is known to have arisen as a result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
6. Treatment with cytotoxic chemotherapeutic agents or experimental agents for the treatment of MDS within 4 weeks of study treatment.
7. Chronic use of systemic corticosteroids for comorbid or study disease condition with in last 4 weeks of study treatment
8. Prior history of malignancy other than MDS (except non-melanoma skin cancer or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for > 3 years.
9. Subject has undergone a stem cell, bone marrow or solid organ transplant
10. Subjects with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
11. Prior treatment with disease modifying agents such as hypomethylating agents, or immunosuppressive therapy or experimental agents other than growth factor for MDS.
12. Participation in any clinical study within 90 days before the first dose of Investigational Product.
13. Loss of greater than or equal to 350 ml of blood within 90 days before the first dose of Investigational Product.
 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
To assess the efficacy of HT-6184 in subjects with lower risk MDS.  16 Weeks & 32 Weeks 
 
Secondary Outcome  
Outcome  TimePoints 
1) To assess the effect of HT-6184 on biomarkers of inflammasome activation in MDS, and changes in clone size of somatic gene mutations
2) To explore potential enhancement of erythroid response by combined therapy of HT-6184 with an erythroid stimulating agent (ESA)
3) To monitor the adverse events and to ensure the safety of subjects after investigational product (IP) administration
 		 16 Weeks & 32 Weeks 
 
Target Sample Size   Total Sample Size="40"
Sample Size from India="26" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   24/11/2023 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  24/11/2023 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Yet Recruiting 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

This study is an open-label, Phase 2a clinical trial evaluating the efficacy and safety of HT-6184 in subjects with very low, low or intermediate risk MDS who are refractory, intolerant of or ineligible for treatment with an ESA.

 

HT-6184 will be self-administered orally using a recurring 7 day schedule in which subjects will receive study drug once daily for five consecutive days followed by a two days drug holiday.

Each treatment cycle consists of 28 days. Subjects will be evaluated for safety if they receive at least one dose of study drug, utilizing an intention-to-treat approach for study analysis.

 

Subjects will be monitored at each cycle for drug tolerance, safety and hematological response. Final response assessment will occur after 16 weeks of study treatment using IWG 2018 criteria (refer Appendix B).

 

Responding subjects may continue treatment thereafter until evidence for loss of response, intolerance or subject’s decision to withdrawal from the study.

 

Non-responders who experience a reduction in clone size (VAF reduced >30% of baseline) at Week 16 and for whom the investigator feels clinical or emerging hematologic benefit may continue monotherapy for up to 16 additional weeks (Week 32) before hematologic response assessment. Subjects not responding to HT-6184 monotherapy at Week 16 (i.e., those subjects with clonal suppression) will be offered to continue HT-6184 combined with their prior ESA. Dosing with epoetin alfa will be 60,000 units subcutaneously (SC) weekly or darbepoetin alpha 300μg SC at every 2 weeks.

Response to and tolerance of the combined regimen will be assessed at study week 32 (i.e., Week 16 combined therapy).

 

Quality of life (QOL) assessments and patient-reported outcomes (PROs) will be collected at protocol-specified time points from all subjects, using the European Organization for Research and Treatment of Cancer Quality-of-Life (EORTC QLQC30) and the Health-related Quality of Life (QOL-E®) questionnaires.

 

 
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