A Study of IMR-687 in Subjects With Sickle Cell Disease

• Sponsor: Imara, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04474314
• Collaborator: (none)
• Enrollment: 115
• Locations: 49
• Arms: 3
• Actual Duration (Months): 20.7
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects with Sickle Cell Disease

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: IMR-687; Drug: Placebo	Phase 2

Detailed Description

A phase 2b, randomized, double-blind, placebo-controlled, multicenter study of subjects with sickle cell disease (SCD; homozygous sickle hemoglobin [HbSS], sickle-β0 [HbSβ0] thalassemia, or sickle-β+ [HbSβ+] thalassemia) to evaluate the safety and efficacy of the phosphodiesterase type 9 (PDE9) inhibitor, IMR-687, administered once daily (qd) for 52 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 115 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double-Blind
• Primary Purpose: Treatment
• Official Title: A Phase 2b Study to Evaluate the Safety and Efficacy of IMR-687 in Subjects With Sickle Cell Disease
• Actual Study Start Date: Aug 13, 2020
• Actual Primary Completion Date: Mar 2, 2022
• Actual Study Completion Date: May 4, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Higher dose IMR-687 Oral administration of once daily IMR-687	Drug: IMR-687; Oral administration of once daily IMR-687
Experimental: Lower Dose IMR-687 Oral administration of once daily IMR-687	Drug: IMR-687; Oral administration of once daily IMR-687
Placebo Comparator: Placebo Oral administration of once daily Placebo	Drug: Placebo; Oral administration of once daily Placebo

Outcome Measures

Primary Outcome Measures

1. Effect on the incidence of vaso-occlusive crises (VOCs) [Baseline to Week 52]

   a. Annualized rate of VOCs

2. Proportion of patients with adverse events and serious adverse events [Baseline to Week 56]

   Incidence of Adverse Events Incidence of Serious Adverse Events

Secondary Outcome Measures

1. Time to first vaso-occlusive crises (VOCs) [Baseline to Week 52]

   a. Time to first VOC

2. Proportion of HbF response [Baseline to Week 24]

   a. Proportion of Subject with response to HbF (absolute increase of ≥3%)

3. Proportion of VOC-free subject [Baseline to Week 52]

4. Annualized rate of hospitalizations for vaso-occlusive crises (VOCs) [Baseline to Week 24, and Week 52]

   a. Annualized rate of hospitalizations for VOCs

5. Time to second vaso-occlusive crises (VOCs) [Baseline to Week 24, and Week 52]

   a. Time to second VOC

6. Proportion of HbF response [Baseline to Week 52]

   a. Proportion of Subject with response to HbF (absolute increase of ≥3%)

7. Change in HbF and F Cells [Baseline to Week 24, and Week 52]

   a. Change in HbF (%) and F-cells (%)

8. Proportion of Subject response in total Hb [Baseline to Week 24, and Week 52]

   a. Proportion of Subject response in total Hb (increase of ≥1.0 g/dL)

9. Change in hemolysis biomarkers [Baseline to Week 24, and Week 52]

   a. Change in hemolysis biomarkers (% and absolute reticulocytes, unconjugated (indirect) bilirubin, and lactate dehydrogenase (LDH)

10. Effect on Quality of Life Measures: Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®) [Baseline to Week 24, and Week 52]

    a. Change in each measured subdomain of the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®).

11. Effect on Quality of Measures: Patient-Reported Outcomes Measurements Information System (PROMIS) [Baseline to Week 24, and Week 52]

    a. The Patient-Reported Outcomes Measurements Information System Preference (PROMIS® 29 + 2 Profile v2.1 [PROPr]).

12. Effect on Quality of Measures: Sickle Cell Self-Efficacy Scale (SCES) [Baseline to Week 24, and Week 52]

    a. Change in overall score of the Sickle Cell Self-Efficacy Scale (SCSES).

13. Changes in biomarker of adhesion [Baseline to Week 24 and Week 52]

    a. Changes in biomarkers of adhesion such as soluble E-selectin, P-selectin, ICAM-1, and VCAM-1

14. Changes in inflammation biomarkers [Baseline to Week 24 and Week 52]

    a. Changes in biomarkers of inflammation such as high-sensitivity C-reactive protein (hsCRP) and myeloperoxidase (MPO)

15. Changes in cardiac stress biomarkers [Baseline to Week 24 and Week 52]

    a. Changes in biomarkers of cardiac stress such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP)

16. Effect on Red Blood Cell (RBC) indices [Baseline to Week 24 and Week 52]

    a. Changes in RBC indices, such as mean corpuscular volume (MCV)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Confirmed diagnosis of SCD (HbSS, HbSB0 thalassemia, or HbSB+ thalassemia)

2. Hemoglobin of >5.5 and <10.5 g/dL; Hb values within 21 days post-transfusion will be excluded.

3. Subjects must have had at least 2 and no more than 12 documented episodes of VOCs in the past 12 months at the time of informed consent signing and at randomization (Day 1).

4. Subjects receiving HU must have received it continuously for at least 6 months prior to signing informed consent, and must have been on a stable dose for at least 3 months prior to signing the informed consent, with no anticipated need for dose adjustments during the study including the screening period, in the opinion of the investigator.

5. Female subjects must not be pregnant or breastfeeding and be highly unlikely to become pregnant. Male subjects must be unlikely to impregnate a partner.

6. Must be willing and able to complete all study assessments and procedures, and to communicate effectively with the investigator and site staff.

Exclusion Criteria:

1. Hospital discharge for sickle cell crisis or other vaso-occlusive event within the 4 days prior to randomization (Day 1).

2. Subjects participating in a chronic/prophylactic RBC transfusion program (i.e., regularly scheduled RBC transfusions); any transfusions within 21 days of screening or baseline Hb measurements

3. Subjects with HbF >25% at screening.

4. Significant kidney disease (eGFR <45mL/min) and liver dysfunction: alanine aminotransferase or aspartate aminotransferase >3x upper limit of normal.

5. Body mass index (BMI) <17.0 kg/m2 and a total body weight <45 kg; or a BMI >35 kg/m2.

6. Subjects with known active hepatitis A, hepatitis B, or hepatitis C, with active or acute event of malaria, or who are known to be positive for human immunodeficiency virus (HIV).

7. Stroke requiring medical intervention within 24 weeks prior to randomization (Day 1).

8. Prior exposure to IMR-687.

9. Subjects taking direct acting oral anti-coagulants (apixaban, dabigatran, rivaroxaban, edoxaban, or ticagrelor) or taking warfarin unless they stopped the treatment at least 28 days prior to randomization (Day 1).

10. A history of use of crizanlizumab (Adakveo®) or voxelotor (Oxbryta®) within 6 months prior to signing the informed consent.

11. Receipt of erythropoietin, luspatercept (Reblozyl®)or other hematopoietic growth factor treatment within 3 months of signing the ICF or anticipated need for such agents during the study.

12. Prior gene therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham School of Medicine - 1917 Clinic	Birmingham	Alabama	United States	35233
2	Arkansas Primary Care Clinic	Little Rock	Arkansas	United States	72204
3	University of California San Diego Moores Cancer Center	La Jolla	California	United States	92093
4	Center For Inherited Blood Disorders	Santa Ana	California	United States	92705
5	The Oncology Institute Long Beach	Whittier	California	United States	90603
6	University of Connecticut Health Main Building	Farmington	Connecticut	United States	06030
7	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30342
8	The University of Illinois at Chicago College of Medicine	Chicago	Illinois	United States	60612-4333
9	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
10	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
11	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
12	Weill Cornell Medicine - Center for Blood Disorders	New York	New York	United States	10021
13	Baylor Scott & White Medical Center-Temple	Temple	Texas	United States	76508
14	Virginia Commonwealth University Health - Ambulatory Care Center	Richmond	Virginia	United States	23219
15	Korle Bu Teaching Hospital	Accra		Ghana	PO Box 77
16	Kintampo Health Research Centre	Kintampo		Ghana	Brong-Ahafo Region
17	Laiko General Hospital of Athens	Athens	Attica	Greece	11526
18	University General Hospital of Patras	Patra		Greece	26504
19	Ippokrateio General Hospital of Thessaloniki	Thessaloníki		Greece	54642
20	Azienda Ospedaliero - Universitaria San Luigi Gonzaga	Turin	Orbassano	Italy	10043
21	Fondazione Policlinico Universitario Agostino Gemelli	Roma	Rome	Italy	00168
22	Ente Ospedaliero Ospedali Galliera	Genoa		Italy	16128
23	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milan		Italy	20122
24	Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello	Palermo		Italy	90146
25	Kenya Medical Research Institute - Kisumu	Kisumu	Nyanza	Kenya	40100
26	Gertrude's Children's Hospital	Nairobi		Kenya	00100
27	The Centre for Respiratory Diseases Research - Kenya Medical Research Institute	Nairobi		Kenya	00100
28	Hopital Nini	Tripoli	North Governorate	Lebanon
29	American University of Beirut Medical Center	Beirut		Lebanon	01107 2020
30	Chronic Care Center	Hazmiyeh		Lebanon
31	Hôpital d'Enfants Rabat	Rabat		Morocco	10100
32	Hagaziekenhuis Van Den Haag - Leyweg	Den Haag	South Holland	Netherlands	2545 AA
33	Sultan Qaboos University Hospital	Muscat		Oman	123
34	Centre National De Transfusion Sanguine - Du Senegal	Dakar		Senegal	5002
35	Hedi Chaker Hospital	Sfax		Tunisia	3089
36	Centre Hôpital Universitaire Farhat Hached	Sousse		Tunisia	4000
37	Centre National de Greffe de la Moelle Osseuse	Tunis		Tunisia	1006
38	Hospital Aziza Othmana	Tunis		Tunisia	1008
39	Jinja Regional Referral Hospital	Jinja		Uganda	PO Box 43
40	Uganda Cancer Institute	Kampala		Uganda	PO Box 3935
41	Makerere University College of Health Sciences	Kampala		Uganda	PO Box 7072
42	Joint Clinical Research Center - Lubowa	Kampala		Uganda	Wskiso District
43	Infectious Diseases Research Collaboration - Tororo	Tororo		Uganda	256
44	University Hospitals Bristol NHS Foundation Trust	Bristol	England	United Kingdom	BS1 3NU
45	University College London Hospitals NHS	London	England	United Kingdom	NW1 2PG
46	Guy's and Saint Thomas' NHS Foundation Trust	London	England	United Kingdom	SE1 9RT
47	King's College Hospital NHS Foundation Trust	London	England	United Kingdom	SE5 9RS
48	Manchester University NHS Foundation Trust	Manchester	England	United Kingdom	M13 9WL
49	Oxford University Hospitals NHS Foundation Trust	Oxford	England	United Kingdom	OX3 7LE

Sponsors and Collaborators

• Imara, Inc.

Investigators

• Study Director: Kenneth Attie, MD, Imara, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imara, Inc.
• ClinicalTrials.gov Identifier: NCT04474314
• Other Study ID Numbers: IMR-SCD-301; 2019-004471-39
• First Posted: Jul 16, 2020
• Last Update Posted: May 13, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imara, Inc.: Sickle Cell Disease
• Additional relevant MeSH terms: Anemia, Sickle Cell

Study Results

No Results Posted as of May 13, 2022