A Study of IMR-687 in Adult Participants With Sickle Cell Anemia (Homozygous HbSS or Sickle-β0 Thalassemia)
Sponsor
Imara, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03401112
Collaborator
(none)
100
13
3
31
7.7
0.2
Study Details
Study Description
Brief Summary
Study of IMR-687 in adult participants with sickle cell anemia (SCA) (homozygous HbSS or sickle-β0 thalassemia).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a proof-of-concept study in adult SCA participants, ages 18 to 55 years old, to examine the safety, tolerability, and pharmacokinetic (PK), as well as the potential pharmacodynamic (PD) effects and clinical efficacy, of IMR-687 across a range of doses.
IMR-687 was administered in 2 populations of participants with SCA: those who were not receiving hydroxyurea (HU) and those who were receiving a stable dose of HU according to standard of care.
Study Design
Study Type:
Interventional
Actual Enrollment
:
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
Double-blind
Primary Purpose:
Treatment
Official Title:
A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study of IMR-687 in Adult Patients With Sickle Cell Anaemia (Homozygous HbSS or Sickle-β0 Thalassemia)
Actual Study Start Date
:
Jan 26, 2018
Actual Primary Completion Date
:
Aug 28, 2020
Actual Study Completion Date
:
Aug 28, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IMR-687 50 mg/100 mg A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants. Duration of administration was 16 (Week 17) or 24 weeks (Week 25). |
Drug: IMR-687
Oral administration of IMR-687 once daily with or without HU.
|
| Experimental: IMR-687 100 mg/200 mg A starting dose of IMR-687 100 mg with dose escalation after 4 or 12 weeks, up to 200 mg was administered to participants. Duration of administration was 24 weeks (Week 25). |
Drug: IMR-687
Oral administration of IMR-687 once daily with or without HU.
|
| Placebo Comparator: Placebo Matching placebo was administered for 16 (Week 17) or 24 weeks (Week 25). |
Drug: Placebo
Oral administration of placebo once daily with or without HU.
|
Outcome Measures
Primary Outcome Measures
- Number Of Participants With Treatment-emergent Adverse Events (TEAEs) And Serious Adverse Events (SAEs) [Day 1 (after dosing) through up to Week 24]
An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An SAE was defined as any AE that resulted in 1 or more of the following outcomes: death, required or prolonged hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, or other medically important event. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Secondary Outcome Measures
- Pharmacokinetic (PK) Of Participants Who Did Not Concomitantly Receive HU: Maximum Plasma Concentration (Cmax) Of IMR-687 [Day 1 and Week 25]
For PK assessments of participants who did not concomitantly receive HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 25) assessments are presented.
- PK Of Participants Who Did Not Concomitantly Receive HU: Area Under The Concentration-time Curve (AUC) From Time 0 To 24 Hours Postdose (AUC0-24h) Of IMR-687 [Day 1 and Week 25]
For PK assessments of participants who did not concomitantly receive HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 25) assessments are presented.
- PK Of Participants Who Concomitantly Received HU: Cmax Of IMR-687 [Day 1 and Week 17]
For PK assessments of participants who concomitantly received HU, serial blood samples for IMR-687 PK were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 17) assessments are presented.
- PK Of Participants Who Concomitantly Received HU: AUC0-24h Of IMR-687 [Day 1 and Week 17]
For PK assessments of participants who concomitantly received HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 17) assessments are presented.
- PK Of Participants Who Concomitantly Received HU: Cmax Of HU [Baseline (1 and 2) and Week 17]
For PK assessments of participants who concomitantly received HU, serial blood samples for HU PK were drawn predose and at 0.5, 1, 1.5, 3, 6, 8, and 10 hours after self-administration of the prescribed dose of HU. HU in the presence (end of treatment [EOT]: Week 17) or absence of IMR-687 (Baselines 1 and 2) are presented. HU concentration data were not sorted with respect to HU dose.
- PK Of Participants Who Concomitantly Received HU: AUC0-24h Of HU [Baseline (1 and 2) and Week 17]
For PK assessments of participants who concomitantly received HU, serial blood samples for HU PK were drawn predose and at 0.5, 1, 1.5, 3, 6, 8, and 10 hours after self-administration of the prescribed dose of HU. HU in the presence (EOT: Week 17) or absence of IMR-687 (Baselines 1 and 2) are presented. HU concentration data were not sorted with respect to HU dose.
Other Outcome Measures
- Change From Baseline In F-Cells [Baseline, EOT (Week 25 for participants without HU and Weeks 17 or 25 for participants with HU)]
Absolute least squares (LS) mean change from baseline at EOT is presented. Change from baseline in pharmacodynamic (PD) biomarkers was analyzed using mixed models for repeated measures with covariate of treatment, visit, treatment-by-visit interaction, and baseline value.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
Male or female participants with confirmed SCA
-
Age 18 to 55 years, inclusive
-
For participants on HU, must have been on a stable dose for at least 60 days prior to screening
Key Exclusion Criteria:
-
Total hemoglobin >12.5 or <6 grams/deciliter
-
Red blood cell transfusion within 60 days of baseline
-
7 hospitalizations for vaso-occlusive crises (VOCs) within the last year
-
Estimated glomerular filtration rate <50 milliliter/minute
-
Aspartate aminotransferase/alanine aminotransferase >3x the upper limit of normal
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCSF Benioff Children's Hospital Oakland | Oakland | California | United States | 94609 |
| 2 | University of Connecticut Health Center | Farmington | Connecticut | United States | 06030 |
| 3 | Foundation for Sickle Cell Disease Research | Hollywood | Florida | United States | 33021 |
| 4 | University of Illinois | Chicago | Illinois | United States | 60612 |
| 5 | Loretto Hospital | Chicago | Illinois | United States | 60644 |
| 6 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
| 7 | Baylor Scott & White Health | Temple | Texas | United States | 76508 |
| 8 | Sandwell & West Birmingham Hospital | Birmingham | United Kingdom | B18 7QH | |
| 9 | Bristol Haematology and Oncology Centre | Bristol | United Kingdom | BS2 8ED | |
| 10 | Royal London Hospital | London | United Kingdom | E1 1BB | |
| 11 | University College London Hospital | London | United Kingdom | NW1 2PG | |
| 12 | Guy's Hospital | London | United Kingdom | SE1 9RT | |
| 13 | Oxford Cancer & Haematology Centre, The Churchill Hospital | Oxford | United Kingdom | OX3 7LE |
Sponsors and Collaborators
- Imara, Inc.
Investigators
- Principal Investigator: Timothy Mant, MB FFPM FRCP, Guy's and St Thomas Hospital CRF
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Imara, Inc.
ClinicalTrials.gov Identifier:
NCT03401112
Other Study ID Numbers:
- IMR-SCD-102
- 2017-000653-39
First Posted:
Jan 17, 2018
Last Update Posted:
Apr 14, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study participants were enrolled at 13 sites in 2 countries (United Kingdom and United States). |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) | Placebo (Without HU) | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) |
|---|---|---|---|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 milligrams (mg) with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were not receiving daily hydroxyurea (HU). | A starting dose of IMR-687 100 mg with dose escalation after 4 or 12 weeks, up to 200 mg was administered to participants who were not receiving daily HU. | Matching placebo was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | Matching placebo was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. |
| Period Title: Overall Study | |||||
| STARTED | 15 | 26 | 22 | 27 | 10 |
| Received at Least 1 Dose of Study Drug | 12 | 26 | 20 | 25 | 10 |
| COMPLETED | 10 | 19 | 11 | 21 | 10 |
| NOT COMPLETED | 5 | 7 | 11 | 6 | 0 |
Baseline Characteristics
| Arm/Group Title | IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) | Placebo (Without HU) | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 100 mg with dose escalation after 4 or 12 weeks, up to 200 mg was administered to participants who were not receiving daily HU. | Matching placebo was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | Matching placebo was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | Total of all reporting groups |
| Overall Participants | 12 | 26 | 20 | 25 | 10 | 93 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
34.7
(8.7)
|
32.0
(9.3)
|
35.2
(8.4)
|
32.4
(9.1)
|
28.8
(7.1)
|
32.8
(8.8)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
8
66.7%
|
17
65.4%
|
12
60%
|
15
60%
|
9
90%
|
61
65.6%
|
| Male |
4
33.3%
|
9
34.6%
|
8
40%
|
10
40%
|
1
10%
|
32
34.4%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||
| Not Hispanic or Latino |
11
91.7%
|
23
88.5%
|
19
95%
|
24
96%
|
9
90%
|
86
92.5%
|
| Not Reported |
1
8.3%
|
1
3.8%
|
0
0%
|
1
4%
|
0
0%
|
3
3.2%
|
| Unknown Ethnicity |
0
0%
|
2
7.7%
|
1
5%
|
0
0%
|
1
10%
|
4
4.3%
|
| Black or African American |
12
100%
|
25
96.2%
|
19
95%
|
24
96%
|
9
90%
|
89
95.7%
|
| Other |
0
0%
|
1
3.8%
|
0
0%
|
0
0%
|
0
0%
|
1
1.1%
|
| Missing |
0
0%
|
0
0%
|
1
5%
|
1
4%
|
1
10%
|
3
3.2%
|
Outcome Measures
| Title | Number Of Participants With Treatment-emergent Adverse Events (TEAEs) And Serious Adverse Events (SAEs) |
|---|---|
| Description | An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An SAE was defined as any AE that resulted in 1 or more of the following outcomes: death, required or prolonged hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, or other medically important event. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. |
| Time Frame | Day 1 (after dosing) through up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who had received any amount of study drug. |
| Arm/Group Title | IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) | Placebo (Without HU) | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) | All IMR-687 | All Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 100 mg with dose escalation after 4 or 12 weeks, up to 200 mg was administered to participants who were not receiving daily HU. | Matching placebo was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | Matching placebo was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | All participants who received IMR-687. | All participants who received placebo. |
| Measure Participants | 12 | 26 | 20 | 25 | 10 | 63 | 30 |
| TEAEs |
12
100%
|
24
92.3%
|
18
90%
|
23
92%
|
10
100%
|
59
63.4%
|
28
NaN
|
| SAEs |
4
33.3%
|
7
26.9%
|
8
40%
|
5
20%
|
3
30%
|
16
17.2%
|
11
NaN
|
| Title | Pharmacokinetic (PK) Of Participants Who Did Not Concomitantly Receive HU: Maximum Plasma Concentration (Cmax) Of IMR-687 |
|---|---|
| Description | For PK assessments of participants who did not concomitantly receive HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 25) assessments are presented. |
| Time Frame | Day 1 and Week 25 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation. |
| Arm/Group Title | IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) |
|---|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 100 mg with dose escalation after 4 or 12 weeks, up to 200 mg was administered to participants who were not receiving daily HU. |
| Measure Participants | 12 | 13 |
| Day 1: Single Dose |
512
(30.1)
|
1130
(33.5)
|
| Week 25: Steady State |
1290
(36.4)
|
2180
(24.1)
|
| Title | PK Of Participants Who Did Not Concomitantly Receive HU: Area Under The Concentration-time Curve (AUC) From Time 0 To 24 Hours Postdose (AUC0-24h) Of IMR-687 |
|---|---|
| Description | For PK assessments of participants who did not concomitantly receive HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 25) assessments are presented. |
| Time Frame | Day 1 and Week 25 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation. |
| Arm/Group Title | IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) |
|---|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 100 mg with dose escalation after 4 or 12 weeks, up to 200 mg was administered to participants who were not receiving daily HU. |
| Measure Participants | 11 | 10 |
| Day 1: Single Dose |
2850
(12.5)
|
6590
(17.7)
|
| Week 25: Steady State |
8420
(24.1)
|
15000
(22.3)
|
| Title | PK Of Participants Who Concomitantly Received HU: Cmax Of IMR-687 |
|---|---|
| Description | For PK assessments of participants who concomitantly received HU, serial blood samples for IMR-687 PK were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 17) assessments are presented. |
| Time Frame | Day 1 and Week 17 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation. |
| Arm/Group Title | IMR-687 50 mg/100 mg (With HU) |
|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. |
| Measure Participants | 13 |
| Day 1: Single Dose |
657
(24.7)
|
| Week 17: Steady State |
1370
(18.6)
|
| Title | PK Of Participants Who Concomitantly Received HU: AUC0-24h Of IMR-687 |
|---|---|
| Description | For PK assessments of participants who concomitantly received HU, serial blood samples for IMR-687 plasma concentrations were drawn predose at 0.5, 1, 1.5, 2, 4, 6, and 8 hours after administration of study drug; and at 24 hours after administration of study drug. Day 1 (single-dose) and steady-state (Week 17) assessments are presented. |
| Time Frame | Day 1 and Week 17 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation. |
| Arm/Group Title | IMR-687 50 mg/100 mg (With HU) |
|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. |
| Measure Participants | 12 |
| Day 1: Single Dose |
3090
(34.0)
|
| Week 17: Steady State |
7300
(16.1)
|
| Title | PK Of Participants Who Concomitantly Received HU: Cmax Of HU |
|---|---|
| Description | For PK assessments of participants who concomitantly received HU, serial blood samples for HU PK were drawn predose and at 0.5, 1, 1.5, 3, 6, 8, and 10 hours after self-administration of the prescribed dose of HU. HU in the presence (end of treatment [EOT]: Week 17) or absence of IMR-687 (Baselines 1 and 2) are presented. HU concentration data were not sorted with respect to HU dose. |
| Time Frame | Baseline (1 and 2) and Week 17 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation. |
| Arm/Group Title | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) |
|---|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were also receiving daily HU. HU doses ranged from 500 to 2000 mg. | Participants who were receiving daily HU were administered placebo. HU doses ranged from 500 to 2000 mg. |
| Measure Participants | 14 | 6 |
| Baseline 1 |
25.3
(36.7)
|
20.6
(87.8)
|
| Baseline 2 |
24.8
(38.1)
|
25.4
(98.6)
|
| Week 17 |
24.5
(55.2)
|
20.5
(127)
|
| Title | PK Of Participants Who Concomitantly Received HU: AUC0-24h Of HU |
|---|---|
| Description | For PK assessments of participants who concomitantly received HU, serial blood samples for HU PK were drawn predose and at 0.5, 1, 1.5, 3, 6, 8, and 10 hours after self-administration of the prescribed dose of HU. HU in the presence (EOT: Week 17) or absence of IMR-687 (Baselines 1 and 2) are presented. HU concentration data were not sorted with respect to HU dose. |
| Time Frame | Baseline (1 and 2) and Week 17 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Analysis population consisted of all participants with sufficient sampling for PK parameter evaluation. |
| Arm/Group Title | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) |
|---|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | Participants who were receiving daily HU were administered placebo. HU doses ranged from 500 to 2000 mg. |
| Measure Participants | 12 | 5 |
| Baseline 1 |
99.2
(32.4)
|
113
(87.7)
|
| Baseline 2 |
103
(30.7)
|
129
(71.7)
|
| Week 17 |
122
(23.0)
|
91.4
(127)
|
| Title | Change From Baseline In F-Cells |
|---|---|
| Description | Absolute least squares (LS) mean change from baseline at EOT is presented. Change from baseline in pharmacodynamic (PD) biomarkers was analyzed using mixed models for repeated measures with covariate of treatment, visit, treatment-by-visit interaction, and baseline value. |
| Time Frame | Baseline, EOT (Week 25 for participants without HU and Weeks 17 or 25 for participants with HU) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who had samples for PD analysis sufficient to obtain at least 1 valid PD observation, without protocol deviations or events that would be expected to affect the PD analysis. |
| Arm/Group Title | IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) | Pooled IMR-687 (Without HU) | Placebo (Without HU) | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) |
|---|---|---|---|---|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 100 mg with dose escalation after 4 or 12 weeks, up to 200 mg was administered to participants who were not receiving daily HU. | All participants administered IMR-687 who were not receiving daily HU. | Matching placebo was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | Matching placebo was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. |
| Measure Participants | 7 | 13 | 20 | 7 | 5 | 1 |
| Least Squares Mean (Standard Error) [percentage of F-cells] |
3.97
(4.07)
|
5.66
(2.87)
|
4.81
(2.48)
|
-6.00
(3.77)
|
-2.49
(6.00)
|
7.38
(15.54)
|
| Title | Number Of Participants With Vaso-occlusive Crisis (VOCs) |
|---|---|
| Description | VOCs include the events of acute painful crisis and acute chest symptoms (includes fever, cough, sputum production, shortness of breath, tachypnea, hypoxia, and chest pain). |
| Time Frame | Day 1 (after dosing) through up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who had received any amount of study drug. |
| Arm/Group Title | IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) | Placebo (Without HU) | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) | All IMR-687 | All Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 100 mg with dose escalation after 4 or 12 weeks, up to 200 mg was administered to participants who were not receiving daily HU. | Matching placebo was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | Matching placebo was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | All participants who received IMR-687. | All participants who received placebo. |
| Measure Participants | 12 | 26 | 20 | 25 | 10 | 63 | 30 |
| Count of Participants [Participants] |
6
50%
|
14
53.8%
|
14
70%
|
10
40%
|
7
70%
|
30
32.3%
|
21
NaN
|
| Title | Time To First VOC Event |
|---|---|
| Description | VOCs include the events of acute painful crisis and acute chest symptoms (includes fever, cough, sputum production, shortness of breath, tachypnea, hypoxia, and chest pain). Time to first VOC event was assessed by Kaplan Meier analysis. For this analysis, HU and without HU population groups were pooled for IMR-687 and placebo. In addition, pooled IMR-687 (all doses) are presented. |
| Time Frame | Day 1 (after dosing) through up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pooled data from the IMR-687 dose groups (IMR-687 50mg/100 mg [Without HU]+ IMR-687 100mg/200 mg [Without HU] + IMR-687 50mg/100 mg [With HU]) and pooled data from the placebo arms (With and without HU) were used to provide a larger sample size for the analysis of time to 1st event. |
| Arm/Group Title | IMR-687 50 mg/100 mg | IMR-687 100 mg/200 mg | All IMR-687 | All Placebo |
|---|---|---|---|---|
| Arm/Group Description | All participants who had a starting dose of IMR-687 50 mg (with HU and without HU) with dose escalation up to 100 mg was administered. | All participants who had a starting dose of IMR-687 100 mg with dose escalation up to 200 mg was administered. | All participants who received IMR-687. | All participants who received placebo. |
| Measure Participants | 37 | 26 | 63 | 30 |
| Median (95% Confidence Interval) [days] |
NA
|
139.00
|
169.00
|
87.00
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | IMR-687 50 mg/100 mg (Without HU), IMR-687 100 mg/200 mg (Without HU), IMR-687 50 mg/100 mg (With HU) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0686 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo (Without HU), IMR-687 50 mg/100 mg (With HU) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0294 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Adverse Events
| Time Frame | Day 1 (after dosing) through up to Week 24 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse event data are presented for each of the following IMR-687 groups which included a brief dose escalation: IMR-687 50mg/100 mg [Without HU], IMR-687 100mg/200 mg [Without HU], IMR-687 50mg/100 mg [With HU] and for each placebo arm. Data are not available by dose escalation within arms. | |||||||||||||
| Arm/Group Title | IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) | Placebo (Without HU) | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) | All IMR-687 | All Placebo | |||||||
| Arm/Group Description | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 100 mg with dose escalation after 4 or 12 weeks, up to 200 mg was administered to participants who were not receiving daily HU. | Matching placebo was administered to participants who were not receiving daily HU. | A starting dose of IMR-687 50 mg with dose escalation after 4 or 12 weeks, up to 100 mg was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | Matching placebo was administered to participants who were receiving daily HU. HU doses ranged from 500 to 2000 mg. | All participants who received IMR-687. | All participants who received placebo. | |||||||
All Cause Mortality |
||||||||||||||
| IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) | Placebo (Without HU) | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) | All IMR-687 | All Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/12 (0%) | 0/26 (0%) | 0/20 (0%) | 0/25 (0%) | 0/10 (0%) | 0/63 (0%) | 0/30 (0%) | |||||||
Serious Adverse Events |
||||||||||||||
| IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) | Placebo (Without HU) | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) | All IMR-687 | All Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/12 (33.3%) | 7/26 (26.9%) | 8/20 (40%) | 5/25 (20%) | 3/10 (30%) | 16/63 (25.4%) | 11/30 (36.7%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Sickle cell anaemia with crisis | 3/12 (25%) | 4 | 7/26 (26.9%) | 8 | 7/20 (35%) | 11 | 3/25 (12%) | 3 | 3/10 (30%) | 3 | 13/63 (20.6%) | 15 | 10/30 (33.3%) | 14 |
| General disorders | ||||||||||||||
| Non-cardiac chest pain | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 0/20 (0%) | 0 | 1/25 (4%) | 1 | 0/10 (0%) | 0 | 1/63 (1.6%) | 1 | 0/30 (0%) | 0 |
| Pyrexia | 0/12 (0%) | 0 | 1/26 (3.8%) | 1 | 0/20 (0%) | 0 | 0/25 (0%) | 0 | 0/10 (0%) | 0 | 1/63 (1.6%) | 1 | 0/30 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||
| Hepatic lesion | 1/12 (8.3%) | 1 | 0/26 (0%) | 0 | 0/20 (0%) | 0 | 0/25 (0%) | 0 | 0/10 (0%) | 0 | 1/63 (1.6%) | 1 | 0/30 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||
| Multiple injuries | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 0/20 (0%) | 0 | 1/25 (4%) | 1 | 0/10 (0%) | 0 | 1/63 (1.6%) | 1 | 0/30 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Uterine leiomyoma | 1/8 (12.5%) | 1 | 0/17 (0%) | 0 | 0/12 (0%) | 0 | 0/15 (0%) | 0 | 0/9 (0%) | 0 | 1/40 (2.5%) | 1 | 0/21 (0%) | 0 |
| Nervous system disorders | ||||||||||||||
| Cerebrovascular accident | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 0/20 (0%) | 0 | 1/25 (4%) | 1 | 0/10 (0%) | 0 | 1/63 (1.6%) | 1 | 0/30 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||
| Ovarian cyst | 0/8 (0%) | 0 | 0/17 (0%) | 0 | 0/12 (0%) | 0 | 1/15 (6.7%) | 1 | 0/9 (0%) | 0 | 1/40 (2.5%) | 1 | 0/21 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Rash generalise | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 1/20 (5%) | 1 | 0/25 (0%) | 0 | 0/10 (0%) | 0 | 0/63 (0%) | 0 | 1/30 (3.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||||
| IMR-687 50 mg/100 mg (Without HU) | IMR-687 100 mg/200 mg (Without HU) | Placebo (Without HU) | IMR-687 50 mg/100 mg (With HU) | Placebo (With HU) | All IMR-687 | All Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/12 (100%) | 22/26 (84.6%) | 16/20 (80%) | 23/25 (92%) | 10/10 (100%) | 57/63 (90.5%) | 26/30 (86.7%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Sickle cell anaemia with crisis | 5/12 (41.7%) | 15 | 9/26 (34.6%) | 15 | 9/20 (45%) | 14 | 10/25 (40%) | 14 | 6/10 (60%) | 23 | 24/63 (38.1%) | 44 | 15/30 (50%) | 37 |
| Ear and labyrinth disorders | ||||||||||||||
| Ear pain | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 1/20 (5%) | 1 | 1/25 (4%) | 1 | 1/10 (10%) | 1 | 1/63 (1.6%) | 1 | 2/30 (6.7%) | 2 |
| Gastrointestinal disorders | ||||||||||||||
| Nausea | 2/12 (16.7%) | 3 | 8/26 (30.8%) | 14 | 0/20 (0%) | 0 | 4/25 (16%) | 4 | 5/10 (50%) | 5 | 14/63 (22.2%) | 21 | 5/30 (16.7%) | 5 |
| Abdominal pain | 0/12 (0%) | 0 | 3/26 (11.5%) | 4 | 1/20 (5%) | 1 | 2/25 (8%) | 3 | 0/10 (0%) | 0 | 5/63 (7.9%) | 7 | 1/30 (3.3%) | 1 |
| Abdominal pain upper | 1/12 (8.3%) | 1 | 2/26 (7.7%) | 2 | 0/20 (0%) | 0 | 2/25 (8%) | 2 | 0/10 (0%) | 0 | 5/63 (7.9%) | 5 | 0/30 (0%) | 0 |
| Vomiting | 1/12 (8.3%) | 1 | 2/26 (7.7%) | 2 | 0/20 (0%) | 0 | 2/25 (8%) | 2 | 1/10 (10%) | 4 | 5/63 (7.9%) | 5 | 1/30 (3.3%) | 4 |
| Diarrhoea | 1/12 (8.3%) | 1 | 0/26 (0%) | 0 | 1/20 (5%) | 1 | 2/25 (8%) | 2 | 1/10 (10%) | 1 | 3/63 (4.8%) | 3 | 2/30 (6.7%) | 2 |
| General disorders | ||||||||||||||
| Fatigue | 1/12 (8.3%) | 1 | 2/26 (7.7%) | 2 | 2/20 (10%) | 2 | 4/25 (16%) | 6 | 2/10 (20%) | 2 | 7/63 (11.1%) | 9 | 4/30 (13.3%) | 4 |
| Influenza like illness | 2/12 (16.7%) | 2 | 2/26 (7.7%) | 3 | 2/20 (10%) | 2 | 2/25 (8%) | 5 | 0/10 (0%) | 0 | 6/63 (9.5%) | 10 | 2/30 (6.7%) | 2 |
| Pain | 2/12 (16.7%) | 2 | 1/26 (3.8%) | 2 | 1/20 (5%) | 2 | 1/25 (4%) | 1 | 0/10 (0%) | 0 | 4/63 (6.3%) | 5 | 1/30 (3.3%) | 2 |
| Oedema peripheral | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 1/20 (5%) | 1 | 0/25 (0%) | 0 | 1/10 (10%) | 1 | 0/63 (0%) | 0 | 2/30 (6.7%) | 2 |
| Hepatobiliary disorders | ||||||||||||||
| Ocular icterus | 1/12 (8.3%) | 1 | 2/26 (7.7%) | 2 | 0/20 (0%) | 0 | 4/25 (16%) | 4 | 1/10 (10%) | 1 | 7/63 (11.1%) | 7 | 1/30 (3.3%) | 1 |
| Jaundice | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 0/20 (0%) | 0 | 1/25 (4%) | 2 | 2/10 (20%) | 3 | 1/63 (1.6%) | 2 | 2/30 (6.7%) | 3 |
| Infections and infestations | ||||||||||||||
| Upper respiratory tract infection | 3/12 (25%) | 5 | 1/26 (3.8%) | 1 | 2/20 (10%) | 2 | 2/25 (8%) | 3 | 2/10 (20%) | 2 | 6/63 (9.5%) | 9 | 4/30 (13.3%) | 4 |
| Nasopharyngitis | 2/12 (16.7%) | 2 | 2/26 (7.7%) | 2 | 1/20 (5%) | 1 | 1/25 (4%) | 1 | 1/10 (10%) | 1 | 5/63 (7.9%) | 5 | 2/30 (6.7%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Back pain | 0/12 (0%) | 0 | 6/26 (23.1%) | 7 | 2/20 (10%) | 2 | 1/25 (4%) | 1 | 2/10 (20%) | 2 | 7/63 (11.1%) | 8 | 4/30 (13.3%) | 4 |
| Arthralgia | 0/12 (0%) | 0 | 4/26 (15.4%) | 5 | 1/20 (5%) | 1 | 2/25 (8%) | 2 | 1/10 (10%) | 1 | 6/63 (9.5%) | 7 | 2/30 (6.7%) | 2 |
| Pain in extremity | 1/12 (8.3%) | 1 | 2/26 (7.7%) | 2 | 2/20 (10%) | 2 | 2/25 (8%) | 3 | 2/10 (20%) | 2 | 5/63 (7.9%) | 6 | 4/30 (13.3%) | 4 |
| Musculoskeletal pain | 1/12 (8.3%) | 1 | 1/26 (3.8%) | 1 | 1/20 (5%) | 1 | 1/25 (4%) | 1 | 1/10 (10%) | 1 | 3/63 (4.8%) | 3 | 2/30 (6.7%) | 2 |
| Nervous system disorders | ||||||||||||||
| Headache | 2/12 (16.7%) | 2 | 8/26 (30.8%) | 11 | 4/20 (20%) | 6 | 12/25 (48%) | 18 | 4/10 (40%) | 6 | 22/63 (34.9%) | 31 | 8/30 (26.7%) | 12 |
| Dizziness | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 1/20 (5%) | 1 | 2/25 (8%) | 2 | 1/10 (10%) | 1 | 2/63 (3.2%) | 2 | 2/30 (6.7%) | 2 |
| Lethargy | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 2/20 (10%) | 3 | 0/25 (0%) | 0 | 0/10 (0%) | 0 | 0/63 (0%) | 0 | 2/30 (6.7%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Oropharyngeal pain | 1/12 (8.3%) | 1 | 1/26 (3.8%) | 1 | 2/20 (10%) | 2 | 1/25 (4%) | 1 | 0/10 (0%) | 0 | 3/63 (4.8%) | 3 | 2/30 (6.7%) | 2 |
| Cough | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 2/20 (10%) | 2 | 0/25 (0%) | 0 | 1/10 (10%) | 1 | 0/63 (0%) | 0 | 3/30 (10%) | 3 |
| Rhinorrhoea | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 1/20 (5%) | 1 | 0/25 (0%) | 0 | 1/10 (10%) | 1 | 0/63 (0%) | 0 | 2/30 (6.7%) | 2 |
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Pruritus | 0/12 (0%) | 0 | 0/26 (0%) | 0 | 2/20 (10%) | 2 | 0/25 (0%) | 0 | 0/10 (0%) | 0 | 0/63 (0%) | 0 | 2/30 (6.7%) | 2 |
| Vascular disorders | ||||||||||||||
| Hot flush | 0/12 (0%) | 0 | 1/26 (3.8%) | 1 | 1/20 (5%) | 1 | 0/25 (0%) | 0 | 1/10 (10%) | 1 | 1/63 (1.6%) | 1 | 2/30 (6.7%) | 2 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Imara Clinical Operations |
|---|---|
| Organization | Imara Inc. |
| Phone | 617-206-2020 |
| info@imaratx.com |
Responsible Party:
Imara, Inc.
ClinicalTrials.gov Identifier:
NCT03401112
Other Study ID Numbers:
- IMR-SCD-102
- 2017-000653-39
First Posted:
Jan 17, 2018
Last Update Posted:
Apr 14, 2022
Last Verified:
Mar 1, 2022