A Randomized, Blinded, Multicenter Study to Evaluate NASHA/Dx for the Treatment of Fecal Incontinence
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the effectiveness and safety of NASHA/Dx when used as an injectable bulking agent in the treatment of fecal incontinence. The study includes a 6-month blinded sham-controlled phase, followed by an open-label phase.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Subjects will be given up to 2 treatments of NASHA/Dx or sham and followed for 6 months from last treatment (ie, one retreatment is permitted at 1 month after the first injection) in the blinded phase of the study. At Month 6, the open phase of the study will begin and subjects on sham will be offered open-label treatment with NASHA/Dx.
Subjects who receive NASHA/Dx at the start of the blinded phase will be followed for up to 36 months from last treatment in the blinded phase. Subjects who receive sham at the start of the blinded phase and then receive open-label NASHA/Dx at Month 6 (start of the open phase) will be followed for another 24 months (equivalent to approximately 30 months from randomization) from last treatment in the open phase of the study.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Blinded injection of NASHA/Dx gel at randomization. Blinded injection of NASHA/Dx (Solesta) Gel. For each treatment, a series of 4 equally spaced injections with 1 mL of Solesta into the anal canal. Subjects will be followed for 6 months during the blinded phase. During a subsequent open phase, these subjects will be followed to Month 36 (ie, for an additional 30 months). |
Device: NASHA/Dx (Solesta) Gel
Injection of 4 x 1ml of NASHA/Dx Gel at the start of the blinded phase.
Other Names:
|
| Sham Comparator: Blinded sham inject. at randomization Blinded sham injection (needle stick with empty syringes). For each treatment, a series of 4 equally spaced Sham injections (needle sticks) into the anal canal. Subjects will be followed for 6 months during the blinded phase. Sham-treated subjects have the option to receive open-label injection of NASHA/Dx (Solesta) Gel at the 6-month time point following completion of the blinded phase (ie, blinded sham injection at randomization + NASHA/Dx Gel at 6 months). Following injection of NASHA/Dx gel at the start of the open phase, these subjects will be followed to Month 30 (ie, for an additional 24 months). |
Device: Sham Injection
Sham injection at the start of the blinded phase.
|
| Other: Blinded Sham Inject. at Randomization + NASHA/Dx Gel at 6 mo. Blinded sham injection at randomization. Subjects will be followed for 6 months during the blinded phase. Sham-treated subjects have the option to receive open-label injection of NASHA/Dx (Solesta) Gel at the 6-month time point following completion of the blinded phase (ie, blinded sham injection at randomization + NASHA/Dx Gel at 6 months). Following injection of NASHA/Dx gel at the start of the open phase, these subjects will be followed to Month 30 (ie, for an additional 24 months). |
Device: NASHA/Dx (Solesta) Gel
Injection of 4 x 1ml of NASHA/Dx Gel at the start of the blinded phase.
Other Names:
Device: Sham Injection
Sham injection at the start of the blinded phase.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Who Are Responder50. [6 months after last blinded treatment]
Percentage of participants who achieve ≥ 50% reduction in the number of fecal incontinence episodes compared to baseline (Responder50).
- Percentage of Participants Who Are Responder25. [12 months after last treatment]
Response to treatment at 12 months was defined as a ≥ 25 % reduction in the number of fecal incontinence episodes compared to baseline (Responder25).
Secondary Outcome Measures
- Number of Fecal Incontinence Episodes [up to 6 months after last treatment]
The number of incontinence episodes collected from a participant incontinence diary spanning a period of 14 days prior to each of the study visits.
- Number of Incontinence Free Days [up to 6 months after last treatment]
The number of days with no fecal incontinence episodes (incontinence free days).
- Change From Baseline in Fecal Incontinence Quality of Life Scale (FIQL). [up to 6 months after last treatment]
The disease-specific Fecal Incontinence Quality of Life (FIQL) questionnaire is designed to capture the impact of treatment on quality of life for participants suffering from fecal incontinence as it pertains to 4 domains: Lifestyle, Coping/Behavior, Depression/Self perception and Embarrassment. The more the subject is affected by fecal incontinence the lower the value. Hence, a positive change from baseline indicates improvement. Scores range from 1 to 4.
- Cleveland Clinic Florida Incontinence Score (CCFIS). [up to 6 months after last treatment]
Cleveland Clinic Florida Incontinence Score (CCFIS) score was based on a participant interview using standardized questions regarding incidence and type of incontinence (solid, liquid or gas), pad usage and lifestyle alterations during the past month. The score ranged from 0 (perfect) to 20 (complete incontinence)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
18-75 years of age, male or female.
-
Screening fecal incontinence severity score (CCFIS).
-
Fecal incontinence episodes over a 14-day period.
-
Failed conservative treatment for fecal incontinence.
Exclusion Criteria:
-
Complete external sphincter disruption.
-
Significant anorectal disease.
-
Anorectal surgery within the last 12 months prior to the study.
-
Active Inflammatory Bowel Disease (IBD).
-
Immunodeficiency or receiving immunosuppressive therapy.
-
Malignancies in remission for less than 2 years prior to the study.
-
Bleeding disorders or receiving anticoagulant therapy.
-
Chemotherapy within the last 12 months prior to the study.
-
Prior Pelvic radiotherapy.
-
Women who are pregnant or breast-feeding, or women of childbearing potential not practicing adequate contraception or planning to stop such contraception within the first year of the study.
-
Women within one year post partum.
-
Participation in any other clinical study within 3 month prior to the study.
-
Hypersensitivity to hyaluronic acid containing products.
-
Other severe conditions or in other ways unsuitable to participate according to investigator judgement.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, San Francisco, Center for Pelvic Physiology, Dept. of Surgery | San Francisco | California | United States | 94115 |
| 2 | University of South Florida College of Medicine, Tampa General Hospital | Tampa | Florida | United States | 33601 |
| 3 | Lahey Clinic, Department of Colon & Rectal Surgery | Burlington | Massachusetts | United States | 01805 |
| 4 | Colon & Rectal Surgery Associates | Minneapolis | Minnesota | United States | 55454 |
| 5 | St. Luke's/Roosevelt Hospital | New York | New York | United States | 10019 |
| 6 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 7 | Colorectal Surgical Associates | Houston | Texas | United States | 77054 |
| 8 | Salt Lake Research/Center for Colon Rectal Disease | Salt Lake City | Utah | United States | 84107 |
| 9 | Chirurgische Klinik Mit Poliklinik, FAU Erlangen-Nurnberg | Erlangen | Germany | 910 54 | |
| 10 | Kirurgmottagningen Universitetssjukhuset MAS | Malmo | Sweden | 205 02 | |
| 11 | Kirurgmottagningen, Danderyds Sjukhus | Stockholm | Sweden | 182 88 | |
| 12 | Kirurgkliniken, Uppsala Akademiska Sjukhus | Uppsala | Sweden | 751 85 | |
| 13 | Castle Hill Hospital, Department of Academic Surgery | Cottingham | East Yorkshire | United Kingdom | HU16 5JQ |
Sponsors and Collaborators
- Bausch Health Americas, Inc.
- Oceana Therapeutics, Inc.
- Galderma R&D
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 33DA0404
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | NashaDx/Fecal | Sham |
|---|---|---|
| Arm/Group Description | NashaDx/Fecal - 4 syringes each containing 1 mL of product | Sham - 4 empty syringes |
| Period Title: Overall Study | ||
| STARTED | 136 | 70 |
| COMPLETED | 129 | 60 |
| NOT COMPLETED | 7 | 10 |
Baseline Characteristics
| Arm/Group Title | NashaDx/Fecal | Sham | Total |
|---|---|---|---|
| Arm/Group Description | NashaDx/Fecal - 4 syringes each containing 1 mL of product | Sham - 4 empty syringes | Total of all reporting groups |
| Overall Participants | 136 | 70 | 206 |
| Age (years) [Mean (Full Range) ] | |||
| Mean (Full Range) [years] |
60.6
|
59.2
|
60.1
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
122
89.7%
|
61
87.1%
|
183
88.8%
|
| Male |
14
10.3%
|
9
12.9%
|
23
11.2%
|
Outcome Measures
| Title | Percentage of Participants Who Are Responder50. |
|---|---|
| Description | Percentage of participants who achieve ≥ 50% reduction in the number of fecal incontinence episodes compared to baseline (Responder50). |
| Time Frame | 6 months after last blinded treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | NashaDx/Fecal | Sham |
|---|---|---|
| Arm/Group Description | NashaDx/Fecal - 4 syringes each containing 1 mL of product | Sham - 4 empty syringes |
| Measure Participants | 136 | 70 |
| Count of Participants [Participants] |
71
52.2%
|
21
30%
|
| Title | Percentage of Participants Who Are Responder25. |
|---|---|
| Description | Response to treatment at 12 months was defined as a ≥ 25 % reduction in the number of fecal incontinence episodes compared to baseline (Responder25). |
| Time Frame | 12 months after last treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome measure was only analyzed for the NASHA/Dx group. |
| Arm/Group Title | NASHA/Dx Fecal |
|---|---|
| Arm/Group Description | NASHA/Dx Fecal - 4 syringes each containing 1 mL of product |
| Measure Participants | 136 |
| Number [percentage of participants] |
69.1
50.8%
|
| Title | Number of Fecal Incontinence Episodes |
|---|---|
| Description | The number of incontinence episodes collected from a participant incontinence diary spanning a period of 14 days prior to each of the study visits. |
| Time Frame | up to 6 months after last treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | NashaDx/Fecal | Sham |
|---|---|---|
| Arm/Group Description | NashaDx/Fecal - 4 syringes each containing 1 mL of product | Sham - 4 empty syringes |
| Measure Participants | 136 | 70 |
| Mean (Standard Error) [number of episodes] |
16.28
(2.15)
|
18.53
(5.56)
|
| Title | Number of Incontinence Free Days |
|---|---|
| Description | The number of days with no fecal incontinence episodes (incontinence free days). |
| Time Frame | up to 6 months after last treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | NashaDx/Fecal | Sham |
|---|---|---|
| Arm/Group Description | NashaDx/Fecal - 4 syringes each containing 1 mL of product | Sham - 4 empty syringes |
| Measure Participants | 136 | 70 |
| Mean (95% Confidence Interval) [incontinence free days] |
7.6
|
6.48
|
| Title | Change From Baseline in Fecal Incontinence Quality of Life Scale (FIQL). |
|---|---|
| Description | The disease-specific Fecal Incontinence Quality of Life (FIQL) questionnaire is designed to capture the impact of treatment on quality of life for participants suffering from fecal incontinence as it pertains to 4 domains: Lifestyle, Coping/Behavior, Depression/Self perception and Embarrassment. The more the subject is affected by fecal incontinence the lower the value. Hence, a positive change from baseline indicates improvement. Scores range from 1 to 4. |
| Time Frame | up to 6 months after last treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome measure was only analyzed for the NASHA/Dx group. |
| Arm/Group Title | NASHA/Dx Fecal |
|---|---|
| Arm/Group Description | NASHA/Dx Fecal - 4 syringes each containing 1 mL of product |
| Measure Participants | 136 |
| Lifestyle domain |
0.29
(0.05)
|
| Coping/Behavior domain |
0.42
(0.05)
|
| Depression/Self perception domain |
0.30
(0.05)
|
| Embarrassment domain |
0.45
(0.06)
|
| Title | Cleveland Clinic Florida Incontinence Score (CCFIS). |
|---|---|
| Description | Cleveland Clinic Florida Incontinence Score (CCFIS) score was based on a participant interview using standardized questions regarding incidence and type of incontinence (solid, liquid or gas), pad usage and lifestyle alterations during the past month. The score ranged from 0 (perfect) to 20 (complete incontinence) |
| Time Frame | up to 6 months after last treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| This outcome measure was only analyzed for the NASHA/Dx group. |
| Arm/Group Title | NASHA/Dx Fecal |
|---|---|
| Arm/Group Description | NASHA/Dx Fecal - 4 syringes each containing 1 mL of product |
| Measure Participants | 136 |
| Mean (Standard Error) [units on a scale] |
-2.45
(0.31)
|
Adverse Events
| Time Frame | 36 months | |
|---|---|---|
| Adverse Event Reporting Description | Adverse events were assessed in all treated subjects and not by treatment group. | |
| Arm/Group Title | Overall | |
| Arm/Group Description | Adverse events were assessed overall and not by randomized treatment group | |
All Cause Mortality |
||
| Overall | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Overall | ||
| Affected / at Risk (%) | # Events | |
| Total | 31/206 (15%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 1/206 (0.5%) | |
| Cardiac disorders | ||
| Atrial fibrillation | 1/206 (0.5%) | |
| Gastrointestinal disorders | ||
| Abdominal pain | 1/206 (0.5%) | |
| Cholelithiasis | 1/206 (0.5%) | |
| Gastroenteritis | 2/206 (1%) | |
| Haemorrhoids | 1/206 (0.5%) | |
| Nausea | 1/206 (0.5%) | |
| Rectal prolapse | 1/206 (0.5%) | |
| Rectal abscess | 2/206 (1%) | |
| E. coli bacteremia | 1/206 (0.5%) | |
| General disorders | ||
| Back pain | 2/206 (1%) | |
| Chest pain | 2/206 (1%) | |
| Enterocele | 1/206 (0.5%) | |
| Infections and infestations | ||
| Pneumonia | 1/206 (0.5%) | |
| Injury, poisoning and procedural complications | ||
| Concussion | 1/206 (0.5%) | |
| Post procedural haematoma | 1/206 (0.5%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 2/206 (1%) | |
| Intervertebral disc protrusion | 2/206 (1%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Benign ovarian tumour | 1/206 (0.5%) | |
| Bladder cancer | 1/206 (0.5%) | |
| Multiple endocrine adenomatosis Type II | 1/206 (0.5%) | |
| Thyroid neoplasm | 1/206 (0.5%) | |
| Nervous system disorders | ||
| Cerebrovascular accident | 1/206 (0.5%) | |
| Vascular disorders | ||
| Arterial senosis limb | 1/206 (0.5%) | |
| Carotid artery stenosis | 1/206 (0.5%) | |
Other (Not Including Serious) Adverse Events |
||
| Overall | ||
| Affected / at Risk (%) | # Events | |
| Total | 78/206 (37.9%) | |
| Gastrointestinal disorders | ||
| Proctalgia | 33/206 (16%) | |
| Rectal haemorrhage | 15/206 (7.3%) | |
| General disorders | ||
| Injection site haemorrhage | 16/206 (7.8%) | |
| Pyrexia | 14/206 (6.8%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Contact sponsor directly for details.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Bausch Health |
| Phone | |
| susan.harris@bauschhealth.com |
- 33DA0404